NICOTINE A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES
J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS
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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2003 by ICON Group International, Inc. Copyright 2003 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1
Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Nicotine: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-83660-4 1. Nicotine-Popular works. I. Title.
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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.
Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail:
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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on nicotine. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.
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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.
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About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes & Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health
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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON NICOTINE .................................................................................................. 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Nicotine....................................................................................... 12 E-Journals: PubMed Central ..................................................................................................... 150 The National Library of Medicine: PubMed .............................................................................. 153 CHAPTER 2. NUTRITION AND NICOTINE ...................................................................................... 329 Overview.................................................................................................................................... 329 Finding Nutrition Studies on Nicotine ..................................................................................... 329 Federal Resources on Nutrition ................................................................................................. 336 Additional Web Resources ......................................................................................................... 337 CHAPTER 3. ALTERNATIVE MEDICINE AND NICOTINE ................................................................ 339 Overview.................................................................................................................................... 339 National Center for Complementary and Alternative Medicine................................................ 339 Additional Web Resources ......................................................................................................... 356 General References ..................................................................................................................... 359 CHAPTER 4. DISSERTATIONS ON NICOTINE .................................................................................. 361 Overview.................................................................................................................................... 361 Dissertations on Nicotine .......................................................................................................... 361 Keeping Current ........................................................................................................................ 364 CHAPTER 5. CLINICAL TRIALS AND NICOTINE ............................................................................ 365 Overview.................................................................................................................................... 365 Recent Trials on Nicotine .......................................................................................................... 365 Keeping Current on Clinical Trials ........................................................................................... 379 CHAPTER 6. PATENTS ON NICOTINE ............................................................................................ 381 Overview.................................................................................................................................... 381 Patents on Nicotine.................................................................................................................... 381 Patent Applications on Nicotine................................................................................................ 461 Keeping Current ........................................................................................................................ 483 CHAPTER 7. BOOKS ON NICOTINE ................................................................................................ 485 Overview.................................................................................................................................... 485 Book Summaries: Federal Agencies............................................................................................ 485 Book Summaries: Online Booksellers......................................................................................... 488 The National Library of Medicine Book Index ........................................................................... 494 Chapters on Nicotine.................................................................................................................. 495 CHAPTER 8. MULTIMEDIA ON NICOTINE ..................................................................................... 503 Overview.................................................................................................................................... 503 Video Recordings ....................................................................................................................... 503 Bibliography: Multimedia on Nicotine ...................................................................................... 506 CHAPTER 9. PERIODICALS AND NEWS ON NICOTINE .................................................................. 509 Overview.................................................................................................................................... 509 News Services and Press Releases.............................................................................................. 509 Newsletter Articles .................................................................................................................... 514 Academic Periodicals covering Nicotine .................................................................................... 517 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 521 Overview.................................................................................................................................... 521 NIH Guidelines.......................................................................................................................... 521 NIH Databases........................................................................................................................... 523 Other Commercial Databases..................................................................................................... 527 APPENDIX B. PATIENT RESOURCES ............................................................................................... 529
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Contents Overview.................................................................................................................................... 529 Patient Guideline Sources.......................................................................................................... 529 Finding Associations.................................................................................................................. 537 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 539 Overview.................................................................................................................................... 539 Preparation................................................................................................................................. 539 Finding a Local Medical Library................................................................................................ 539 Medical Libraries in the U.S. and Canada ................................................................................. 539
ONLINE GLOSSARIES................................................................................................................ 545 Online Dictionary Directories ................................................................................................... 547 NICOTINE DICTIONARY .......................................................................................................... 549 INDEX .............................................................................................................................................. 635
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FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with nicotine is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about nicotine, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to nicotine, from the essentials to the most advanced areas of research. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on nicotine. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to nicotine, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on nicotine. The Editors
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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.
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CHAPTER 1. STUDIES ON NICOTINE Overview In this chapter, we will show you how to locate peer-reviewed references and studies on nicotine.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and nicotine, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “nicotine” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •
Effects of Acute Subcutaneous Nicotine on Attention, Information Processing and Short-Term Memory in Alzheimer's Disease Source: Psychopharmacology. 108(4): 485-494. 1992. Summary: This journal article describes a single blind, placebo controlled study of the effects of acute subcutaneous nicotine on attention, information processing, and short term memory in patients with Alzheimer's disease. The study subjects were 22 patients with Alzheimer's disease, 24 older normal controls, and 24 young normal controls. Each subject participated in a series of seven test sessions which followed a consistent order: an undrugged baseline session, placebo, 0.4 mg nicotine, 0.6 mg nicotine, 0.8 mg nicotine, placebo, and final undrugged session. Computerized tests of rapid visual information processing, delayed response matching to location order, simple and complex reaction time, critical flicker fusion, and digit span were conducted at each
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session. Nicotine administration significantly improved sustained visual attention, reaction time, rapid visual information processing, and perception but did not improve auditory or visual short term memory. There were no consistent differences in patterns of performance between smokers and non smokers in the control groups or between men and women in any group. The implications for future research efforts are discussed. 41 references. •
Transdermal Nicotine for Mildly to Moderately Active Ulcerative Colitis: A Randomized, Double-Blind, Placebo-Controlled Trial Source: Annals of Internal Medicine. 126(5): 364-371. March 1, 1997. Summary: This article reports on a study undertaken to determine the efficacy of transdermal nicotine for controlling clinical disease activity in active ulcerative colitis (UC), a type of inflammatory bowel disease (IBD). The doubleblind, placebo controlled design studied 64 nonsmoking patients with mildly to moderately active UC despite the use of medication. Patients were stratified on the basis of smoking history, extent of disease, and concomitant medical therapy. After stratification, patients were randomly assigned to daily treatment with transdermal nicotine (n = 31) at the highest tolerated dose (11 mg for 1 week and then less than 22 mg for 3 weeks) or placebo (n = 33). Clinical features were assessed at baseline and at 4 weeks by endoscopy, physician assessment, and a patient diary of daily symptoms. At 4 weeks, 12 of 31 patients (39 percent) who received nicotine showed clinical improvement compared with 3 of 33 patients (9 percent) who received placebo. Four patients receiving nicotine discontinued therapy because of side effects (contact dermatitis, nausea, acute pancreatitis). The authors conclude that transdermal nicotine administered at the highest tolerated dosage for 4 weeks is efficacious for controlling clinical manifestations of mildly to moderately active UC. The authors briefly consider the phenomenon of 'opposite effects' wherein smoking adversely affects Crohn's disease (another type of IBD). 2 figures. 4 tables. 21 references. (AA-M).
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Nicotine for Colitis: The Smoke Has Not Yet Cleared (editorial) Source: New England Journal of Medicine. 330(12): 856-857. March 24, 1994. Summary: As the search for the cause of inflammatory bowel disease (IBD) continues, the association between cigarette smoking and a more favorable clinical course in ulcerative colitis remains the sole epidemiologic feature that distinguishes it from Crohn's disease. This article reviews the developments in this area. Topics include the potential effects of smoking on the gastrointestinal tract; current therapies for ulcerative colitis, including drug therapy; anecdotal and uncontrolled clinical studies that indicate that the resumption of smoking or the administration of nicotine may ameliorate ulcerative colitis; the elusive nature of the mechanism of the nicotine effect; and managing patients for whom drug therapy is not successful. The author also comments on a report by Pullan, et al., in this same issue and concludes that the paper does not provide convincing evidence of a true biologic effect of nicotine. 7 references.
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Efficacy of Computer-tailored Smoking Cessation Material as a Supplement to Nicotine Patch Therapy Source: Drug and Alcohol Dependence. 64(1):35-46, September 1, 2001. Summary: Researchers examined the efficacy of computer-tailored cessation materials as a supplement to nicotine patch therapy. The program, Committed Quitters Program (CQP), is a computer-tailored set of printed behavioral support materials offered free to
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purchasers of NicoDerm patches as a supplement to the nicotine patch and the standard brief User Guide (UG) and audiotape. Potential participants for the program were United States purchasers of NicoDerm patches and were recruited when they called a toll free number that offered free behavioral support materials. Eligible callers had to meet the following criteria: (1) Have a target quit date that was within 7 days from the enrollment call date; (2) had not already quit for longer than 1 day; (3) were trying to stop smoking; (4) had been smoking more than 10 cigarettes per day; (5) had purchased NicoDerm CQ Step 1 (a patch containing 21 milligrams of nicotine indicated for those who smoke more than 10 cigarettes/day); (6) agreed to be contacted for followup calls at 6 and 12 weeks; and (7) were at least 18 years old. The toll-free number received 20,696 calls. Of these, 6,426 callers met the eligibility criteria and 3,683 agreed to participate. Of these, 1,854 were randomly assigned to receive the CQP and 1,829 to receive only the UG (control participants). CQP program usage was defined in terms of (1) the amount of the program materials read; (2) frequency of referring to the materials; and (3) perceived helpfulness of, and satisfaction with, the materials. Across all participants, 80.1 percent used their assigned materials. Utilization rates were significantly higher for CQP than for UG participants, 84.1 versus 76.8 percent. Abstinence rates did not differ significantly between all CQP and UG participants at either time point. Among the 80.1 percent of participants who reported using their assigned materials, abstinence rates were significantly higher among CQP than among UG participants at both 6 weeks (38.8 versus 30.7 percent) and 12 weeks (18.2 versus 11.1 percent). Researchers conclude that among those who used it, the CQP proved to be an effective behavioral treatment for improving smoking cessation rates. 5 tables, 29 references. •
Computer Tailored Intervention for Older Smokers Using Transdermal Nicotine Source: Tobacco Control. 9(Supplement 1):i53, 2000. Summary: Researchers describe the initial outcomes of a randomized controlled trial evaluating the efficacy of a self-help intervention combining a quit smoking guide designed for older adults with a series of personalized computer tailored cessation messages. To test the efficacy of this combined targeted and tailored intervention, 470 smokers age 65 and older who filled a transdermal nicotine prescription through Pennsylvania Pharmaceutical Assistance Contract for the Elderly (PACE) were randomly assigned to receive either usual care or a copy of the tailored Clear Horizons guide for older smokers and a series of seven personalized computer generated mailings. Tailored messages were based on past research identifying the factors associated with general quitting success and with patch assisted quitting among older smokers. Subjects were mostly female, white, and had not completed high school. Their mean age was 72, and they had smoked, on average, for more than 50 years. They currently smoked a mean of 22 cigarettes a day, and 75 percent said they smoked within 30 minutes of awakening. Six-month followup data showed that the treatment group subjects were more likely than control group subjects to make at least one serious quit attempt, and to report 7-day point prevalence abstinence. About half of the subjects read all or most of the guide and the mailings. At 12 months, the treatment group still reported significantly more quit attempts (88 percent versus 82 percent), but group differences in quit rates were no longer significant, 33 versus 31 percent. These results show promise for integrating computer-tailored messages into the treatment of older adult smokers. 5 references.
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Free Nicotine Patches plus Proactive Telephone Peer Support to Help Low-income Women Stop Smoking Source: Preventive Medicine. 31(1):68-74, July 2000. Summary: Researchers examined the effectiveness of a program offering free nicotine patches plus proactive peer support to help low-income women stop smoking. They enrolled 214 Medicaid-eligible women, age 18 to 50, who were permanent residents of Chittenden County, Vermont, and who smoked more than four cigarettes per day in the study. Participants had responded to flyers placed on public bulletin boards throughout the county offering free nicotine patches. The women were randomized to receive (1) free nicotine patches in the mail plus proactive support by telephone from a female exsmoker for up to 3 months (106 women, the intervention group); or (2) the free nicotine patches only (108 women, the comparison group). During each telephone call with the women in the intervention group, the support person (1) provided encouragement, guidance, and major reinforcement for quitting smoking; and (2) helped the women cope with high-risk smoking situations using a semistructured protocol. Participants received a mean of seven support calls during the 3-month period. Researchers conducted assessments by telephone at baseline (enrollment) and at 10 days and 3 and 6 months after enrollment. For each call, the support person recorded (1) the date and duration of the call, (2) the woman's current smoking status, (3) whether or not she was currently using the patches, and (4) the major issues discussed during the call. The mean age of the 214 participants was 33 years. They had a mean of 12.5 years of education and a mean annual household income of $12,806. They smoked an average of 23.7 cigarettes/day. Ninety percent of the women were Caucasian. At the end of the experimental period, significantly more women in the intervention group had quit smoking than in the comparison group, 42 versus 28 percent. Similarly, significantly more women in the intervention group had stopped smoking at both the 10-day and 3month assessment points than women in the comparison group, 32 versus 19 percent. No significant differences in smoking cessation were found at the 6-month point; however, the smoking cessation rate was 23 percent in the intervention group and 19 percent in the comparison group. Researchers conclude that this study has demonstrated that proactive telephone peer support in conjunction with free nicotine patches enhances short-term smoking cessation among low-income women of childbearing age. 3 tables, 18 references.
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Telephone Counseling as Adjuvant Treatment for Nicotine Replacement Therapy in a Real-world Setting Source: Preventive Medicine. 31(4):357-363, October 2000. Summary: Researchers tested the feasibility of a proactive counseling strategy for nicotine replacement therapy (NRT) users. Participants included 8,832 NRT users who called the California Smokers' Helpline, a statewide cessation service that provides proactive counseling, one session before NRT use and multisessions after the smokers received NRT. After receiving NRT, some participants discontinued the counseling while others continued with followup sessions. Researchers reviewed 664 of the 8,832 participants 13 months later for quitting status. After receiving NRT, 79 percent of the participants continued with counseling and received 4.2 sessions on average, while 21 percent received only one session. Overall, 82.8 percent of all participants made a quit attempt. Nicotine patch users were more likely to make an attempt than nicotine gum users (85.2 versus 66.3 percent), but the relapse probability was the same for these attempts. Those who received multiple counseling were more likely to make an attempt than those receiving single counseling (84.4 versus 77.1 percent) and were more likely to
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stay quit for 1 year (25.6 versus 16.1 percent). The researchers conclude that proactive telephone counseling is a promising adjuvant treatment for NRT users in a real-world setting and a convenient referral service for supporting health plans or physicians who advise their patients to quit smoking. 1 figure, 2 tables, 33 references. •
Is Telephone Counselling a Useful Addition to Physician Advice and Nicotine Replacement Therapy in Helping Patients to Stop Smoking? A Randomized Controlled Trial Source: Canadian Medical Association Journal. 160(11):1577-1581, June 1, 1999. Summary: Canadian researchers evaluated the benefits of telephone counseling by nurses in addition to physician advice, nicotine replacement therapy, and self-help material for helping patients quit smoking. They recruited volunteers age 18 or older who smoked at least 15 cigarettes daily during the past year, and who wanted to quit smoking within 30 days. At a screening session, the participants received advice on the importance of smoking cessation, gave a medical and smoking history, and had a physical examination. The researchers stratified the participants by age and nicotine dependence, then randomized them to either a usual care group or a usual care group plus telephone counseling. Usual care included (1) nicotine replacement therapy, (2) self-help materials, and (3) physician advice. Telephone counseling by trained nurses occurred at 2 weeks, 6 weeks, and 13 weeks after the target quit date. All participants received questionnaires at 4 weeks, 12 weeks, 26 weeks, and 52 weeks after the target quit date to assess abstinence. Of 453 persons who responded to recruitment attempts, 396 participated, of which 199 were in the control group and 197 were in the intervention group. Results showed that (1) baseline characteristics and participation rates of the participants did not differ significantly between groups; (2) of 337 participants contacted 1 year after the target quit date, 94 reported not smoking; (3) overall quit rates were 45.9 percent at 4 weeks, 36.1 percent at 12 weeks, 28.5 percent at 26 weeks, and 23.8 percent at 52 weeks; and (4) the quit rates did not differ between groups at 52 weeks. The researchers concluded that (1) the addition of three telephone counseling sessions with a nurse did not increase smoking quit rates beyond the 23.7 percent achieved with brief physician advice and nicotine replacement therapy, (2) brief intervention by physicians can have a positive impact on heavy smokers, and (3) more research may show that telephone counseling may help smokers receiving little or no help from physicians. 1 figure, 3 tables, 34 references.
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Telephone-based Support Program for Over-the-counter Nicotine Patch Users Source: Canadian Journal of Public Health. 90(6)397-398, November-December 1999. Summary: Canadian researchers investigated the effectiveness of a telephone-based support program for people who used the over-the-counter nicotine patch. The Stop Smoking Now! (SSN!) program is provided at no additional cost to Nicotrol purchasers. Participants register by calling a toll-free number. Background data on smoking history, demographics, and expected quit date are collected. Callers receive a self-help booklet and a series of informational pamphlets within 3 days of registration. The booklet identifies coping strategies for quitting and remaining smoke-free. The informational pamphlets, in English and French, cover (1) managing withdrawal reactions, urges, and cravings; (2) dealing with weight gain/increased appetite; (3) handling stress and negative emotions; (4) developing social support; and (5) handling relapse. Participants receive four telephone calls from trained nurse-counselors using a scripted intervention. They are contacted on weeks 1, 2, 5, and 10 after their target quit data and offered encouragement, advice, and assistance consistent with their reported actions and
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intentions. Researchers followed 258 people (predominantly females) who registered for SSN! between June and September 1998. They examined data provided by participants to the SSN! program, reviewed self-reported smoking status information recorded by telephone counselors, and telephoned participants an average of 34 weeks after their quit date to determine self-reported smoking status. Data analysis indicated that the over-the-counter nicotine replacement users achieved quit rates at 1, 2, 5, 10, and 34 weeks of 68.2 percent, 64.7 percent, 58.9 percent, 51.2 percent, and 36.2 percent, respectively. Almost two-thirds of this study's participants had made previous quit attempts. Participants perceived most of the program components to be helpful. They considered the telephone counseling the most helpful component, followed by the patch, self-help booklet, mailed materials, and wallet coping card, in descending order. The researchers noted that although there is preliminary evidence of a positive program effect and positive attitudes about program usefulness, they cannot draw firm conclusions because of lack of a control group. 3 tables, 20 references. •
Stages of Change Theory and the Nicotine-dependent Client: Direction for Decision Making in Nursing Practice Source: Clinical Nurse Specialist. 13(1):18-22, January 1999. Summary: The author discusses the role of the stages of change (SOC) theory in nurseled smoking cessation programs. The discussion (1) describes the SOC theory, (2) considers how nurses can use the theory to help nicotine-dependent patients stop smoking, and (3) describes criteria that can be used to evaluate SOC-based smoking cessation programs. SOC theory is based on the assumption that smoking cessation is a decision-based process. It identifies five stages of change: (1) Precontemplation, (2) contemplation, (3) preparation, (4) action, and (5) maintenance. Researchers have shown that behavioral change interventions have different effects depending on which stage of change the client is in. This points to the importance of having interventions that are specific to the stage of change and tailored toward the individual. The concept of relapse is identified within the SOC theory not as a specific stage of change, but rather as part of the behavioral change process. Rather than conceptualizing relapse as a demoralizing event, theorists view relapse as a valuable learning experience. SOC theory can provide a framework for decision making in nursing practice directed at smoking cessation. Criteria established by Chinn and Kramer can be used to systematically evaluate SOC theory-based interventions. These criteria include (1) clarity, (2) simplicity, (3) generality, (4) accessibility, and (5) importance. Examples of how smoking cessation programs can be evaluated using these criteria are provided. 1 table, 22 references.
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Smoking Cessation Among Inner-City African Americans Using the Nicotine Transdermal Patch Source: Journal of General Internal Medicine. 13(1):1-8, January 1998. Summary: Researchers conduct a double-blind, placebo-controlled, randomized trial to evaluate the efficacy of the nicotine patch as an adjunct to brief counseling and education in an inner-city black population recruited from a large hospital serving lowincome patients. Those included (1) smoked at least 10 cigarettes a day for at least the past year, (2) tried to quit at least once, (3) weighed more than 100 pounds, and (4) was self-motivated to quit smoking. Researchers told the patients how to use the patches, both placebo and transdermal nicotine, according to the study's 10-week schedule and nicotine dosage of 21 milligram (mg) per day for 6 weeks, 14 mg/day for 2 weeks, followed by 7 mg/day for 2 weeks. Placebo patches delivered less that 1 mg/day. Patients recorded their patch use and number of cigarettes smoked to document
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adherence to the patch schedule. At the screening visit, the patients received Pathways to Freedom: Winning the Fight Against Tobacco, a culturally-sensitive manual written at the sixth grade level. This manual has three parts: (1) Characteristics of cigarette smoking among blacks, (2) instructions on how to quit, and (3) suggestions for how communities can fight tobacco addiction. The patients also received an audiocassette on the nicotine patch. Smoking cessation was defined as self-reported abstinence since the last visit. The main outcome measure at 6 months was continuous abstinence from the end of patch treatment. Through questionnaires, researchers gathered data on age, gender, educational level, income, marital status, and employment status. They also obtained insurance status and prevalence of chronic diseases. Of the 833 eligible patients, 205 were randomized to each group of the study. At 10 weeks, quit rates were 21.5 percent in the nicotine patch group and 13.7 percent in the placebo group. At 6 months, the quit rates were 17.1 percent in the patch group and 11.7 percent in the placebo group. Adherence for return visits was 83 percent, 78 percent, 55 percent, 52 percent, and 31 percent at 1, 2, 6, and 10 weeks and at 6 months, respectively. At 6 months, 63 percent of patients on the patch and 44 percent of those on the placebo correctly identified which patch they were using. No differences existed in adverse effects. The transdermal nicotine patch significantly improved short-term smoking cessation rates in inner-city blacks, despite poor retention for followup. 1 figure, 3 tables, 47 references. •
Nicotine Replacement: A New Approach to Reducing Tobacco-related Harm Source: European Respiratory Journal. 11(2):473-479, February 1998. Summary: The authors express their point of view on use of nicotine replacement to reduce tobacco-related harm. While many smokers indicate they want to quit, many more say they want to cut back on the number of cigarettes they smoke each day. The harmful effects of tobacco are discussed in relation to cancer, pulmonary disease, cardiovascular disease, and complications during pregnancy. Reduced smoking is not presented as an end goal, but as an intermediate step toward reducing the incidence of these harmful effects. Decreasing the number of cigarettes smoked does not have a direct correlation to the inhalation of harmful substances, as the smoker frequently smokes each cigarette more intensely. A 50 percent reduction in the number of cigarettes smoked actually amounts to about a 30 percent decrease in the intake of toxic substances. The authors review two studies that examined the usefulness of nicotine replacement medications. These studies concluded that large reductions in cigarette smoking and exhaled carbon monoxide levels were achieved and maintained. Only a few studies have looked at the long-term effects of using nicotine medication to reduce smoking. One study involving 3,000 smokers showed no increase in the incidence of cardiovascular events for those using a nicotine gum, even if they continued to smoke. Similarly, no increase in perinatal events has been shown in pregnant women using either the gum or the patch. The following individuals are appropriate targets for smoking reduction: (1) Those who are failing at attempts to stop, (2) those who would like to quit but cannot stop, and (3) those who do not want to quit but do want to reduce smoking. A goal for the practical implementation of a reduced smoking program would be to achieve a 50 percent reduction in the number of cigarettes used each day within a few weeks of starting on the program. A moderately beneficial effect on mortality from ischemic heart disease and lung cancer was reported in a study. Thousands of lives could be saved by a 50 percent reduction in smoking. 2 tables, 50 references.
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Transdermal Nicotine Replacement Smoking Cessation Therapy Source: Annals of Pharmacotherapy. 32(2):264-266, February 1998. Summary: The authors address the issue of whether transdermal nicotine replacement smoking therapy should be used by patients with heart disease by reviewing the effects of cigarette smoking on heart disease, the efficacy of transdermal nicotine therapy, and the use of transdermal nicotine in patients with preexisting cardiac disease. Smoking cessation without the use of drug therapy has been shown to decrease mortality associated with coronary heart disease. The literature also supports beneficial effects of transdermal nicotine patches on cardiovascular parameters, including systolic blood pressure, heart rate, and lipoprotein levels. In theory, transdermal nicotine patch therapy should be less harmful than smoking by providing more stable plasma nicotine concentrations, which should cause fewer sympathomimetic effects, and by eliminating the harmful effects of other nonnicotine cigarette components. Two studies have been conducted examining the use of transdermal nicotine patches in patients with cardiac disease. Both of these studies demonstrated that the transdermal nicotine patch could be safely used in patients with stable coronary artery disease and in certain patients with other types of cardiac disease. 14 references.
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Effectiveness of Nicotine-containing Gum in the Physician-delivered Smoking Intervention Study Source: Preventive Medicine. 27(2):262-267, March-April 1998. Summary: Researchers test the role of nicotine-containing gum (NCG) combined with brief physician counseling in smoking cessation in the Physician-Delivered Smoking Intervention Project (PDSIP), which included 1,286 adult smokers seen by 196 residents at five clinics affiliated with the University of Massachusetts Medical School. About 85 percent of the patients had attempted quitting at least once in the past. Patients in the PDSIP were assigned to one of three groups: (1) Advice only, (2) counseling, and (3) counseling plus NCG. This report includes data only from the latter. Of the 398 original participants in this group, 299 remained for followup. Of these, (1) 172 accepted and received one box of NCG; (2) 19 refilled their prescription only once; (3) 24 refilled their prescription twice; and (4) of the 172 subjects who accepted NCG, 36.8 percent (53 patients) reported using the gum for more than 7 days. Predictors of refilling a prescription were (1) having smoked for 17 years or more, (2) having social support to quit, and (3) being a general medicine patient. At the 6-month followup, 37 percent of those who refilled their NCG prescription had quit smoking compared with 19 percent of those who only picked up the initial prescription and with 20 percent who refused the prescription. Predictors of 6-month smoking cessation among NCG users were (1) having had a quit period over 3 months, (2) abstinence from smoking when feeling ill, and (3) absence of smoking-related physical complaints the month prior to the intervention. Researchers conclude that the amount of NCG use combined with physician-delivered smoking cessation counseling may have helped smokers quit. 4 tables, 28 references.
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Nicotine Dependency and Adolescents: Preventing and Treating Source: Primary Care. 25(1):1-19, March 1998. Summary: The authors describe adolescent tobacco use, research on tobacco cessation for youth, and tobacco use prevention and treatment methods. According to results from the Youth Risk Behavior Survey and other sources, more than 3,000 adolescents become regular smokers every day and at least 6 million adolescents are currently
Studies 11
smokers, despite comprehensive health education efforts. Cigarettes and smokeless tobacco are equally addictive because they both contain nicotine, which acts on the central nervous system and fulfills the criteria for drug dependence. Adolescents follow a similar nicotine addiction pattern to adults. Nicotine may serve as a precedent to other, more harmful drugs. Research, including focus groups, shows that adolescents do intend to quit using tobacco products. Few studies have been conducted on adolescent smoking cessation, but school-based cessation programs have been developed. Programs designed for adolescents who have already begun to use tobacco are based on five stages of smoking behavior: (1) Preparatory stage, (2) initial trying, (3) experimentation stage, (4) regular smoking, and (5) nicotine addiction. Adolescent tobacco intervention is based on the stages of change theory. An adolescent's current stage of change is based on (1) social influences; psychological factors, such as depression, negative affect, or self-efficacy building; and (3) addiction. The motivational interviewing style used in adolescent tobacco cessation programs guides the overall process of interaction between the provider and the adolescent. Five principles underlie motivational interviewing: (1) Express sympathy, (2) develop discrepancy, (3) avoid argumentation, (4) roll with resistance, and (5) support self-efficacy. It is also important to (1) ask open-ended questions, (2) listen reflectively, (3) affirm, (4) summarize, and (5) elicit self-motivational statements. The authors emphasize the need to tailor adolescent tobacco prevention and treatment interventions to the individual based on his or her stage of change and level of use. 44 references. •
Nicotine Dependence Among Adolescent Smokers Source: Archives of Pediatrics and Adolescent Medicine. 152(2):151-156, February 1998. Summary: Researchers conducted a cross-sectional survey of 2,197 10th grade students in 6 San Jose, California, high schools to assess nicotine dependence among adolescent smokers. Students completed a questionnaire that measured (1) cigarette use within the last 30 days; (2) history of attempts to quit smoking; (3) nicotine dependence, using modified questions from the Fagerstrom Tolerance Questionnaire (mFTQ); (4) subjective withdrawal symptoms; and (5) symptoms of depression, using the Center for Epidemiologic Studies Depression Scale (CES-D). Researchers determined saliva cotinine levels and body mass index (BMI). Of the 485 students who reported smoking at least part of 1 cigarette during the past 30 days, 249 reported a previous attempt to quit smoking. Students who had tried to quit in the past reported withdrawal symptoms, which included (1) craving (45.5 percent), (2) nervous and tense (32.8 percent), (3) restless (29.4 percent), (4) irritable (28.7 percent), (5) hungry (25.3 percent), (6) unable to concentrate (21.7 percent), (7) miserable and sad (15.3 percent), and (8) trouble sleeping (12.8 percent). Students who reported strong cravings during a previous attempt to quit had significantly higher mFTQ scores, higher CES-D scores, and higher saliva cotinine levels. Researchers found no significant differences between males and females in the reporting of specific withdrawal symptoms. BMI was not associated with nicotine dependence. Smokers who attempted to quit had higher CES-D scores than nonsmokers, and CES-D scores were significantly associated with the number of reported withdrawal symptoms. Female smokers who attempted to quit had significantly higher CES-D scores. The researchers conclude that use of mFTQ scores, withdrawal symptoms, CES-D scores, and saliva cotinine levels may be helpful in designing smoking cessation programs for adolescents. 1 figure, 2 tables, 37 references.
12 Nicotine
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Transdermal Nicotine Therapy and Primary Care: Importance of Counseling, Demographic, and Participant Selection Factors on 1-Year Quit Rates Source: Archives of Family Medicine. 7(5):425-430, September-October 1998. Summary: Researchers evaluated the smoking cessation efficacy of nicotine patch therapy as an adjunct to low-intensity, primary care intervention. This randomized, placebo controlled, double-blind, multisite trial occurred at 21 primary care sites in Nebraska and involved 369 smokers of 20 or more cigarettes per day who were identified by their family physician. At the beginning of the study, participants completed a brief questionnaire that focused on tobacco dependency and cigarette use, and they rated their motivation to quit. They were asked to set a quit date within 2 weeks of the visit. Participants were randomly assigned to receive nicotine patches or placebo patches; 184 received a 2-week supply of nicotine patches and 185 received placebo patches. They received a support booklet on quitting and were asked to return within 1 week of their designated quit date. At that visit, they provided a rating of overall tobacco withdrawal symptoms and received the remaining 8-week supply of patches. Researchers made telephone contact for followup visits with participants at 3 months, 6 months, and 1 year after their quit date. During the first call, participants were informed that they were eligible for $75 if they came to the university site to relate their experiences with the patch. At the 3-month visit, smoking status was assessed, and participants recorded the date since no cigarettes (if applicable). They also discussed how they initially heard about the study and how much counseling they received at the family practice sites. Participants noted all adverse events that occurred during the treatment phase, and completed an exhaled carbon monoxide measurement test and provided a saliva sample for measuring cotinine levels. Data analysis indicated that nicotine patch therapy enhanced 6-month quit rates as an adjunct to brief primary care intervention. The data clearly indicated that counseling maximized smoking cessation rates with the nicotine patch. Several demographic factors seemed to affect quit rates. The highest quit rates were achieved by participants who specifically contacted the site to enroll in the study or to obtain a prescription for nicotine patches. Individuals who were older or had higher nicotine dependency scores were better candidates for nicotine replacement treatment. 5 figures, 14 references.
Federally Funded Research on Nicotine The U.S. Government supports a variety of research studies relating to nicotine. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to nicotine.
2 Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
Studies 13
For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore nicotine. The following is typical of the type of information found when searching the CRISP database for nicotine: •
Project Title: A CLINICAL TRIAL OF TWO MEDICATIONS ON SMOKING CESSATION Principal Investigator & Institution: Johnson, Karen C.; Associate Professor of Medicine; Preventive Medicine; University of Tennessee Health Sci Ctr Health Science Center Memphis, TN 38163 Timing: Fiscal Year 2002; Project Start 07-JAN-2002; Project End 31-DEC-2006 Summary: (provided by applicant): Cigarette smoking poses a serious but preventable health risk. Even though the detrimental effects of smoking are well known, the prevalence of cigarette smoking remains high in the U.S., particularly for younger persons, persons of lower socioeconomic status, and minority groups. Although some persons quit smoking on their own or with the help of behavioral smoking cessation interventions, there are a substantial number of smokers who are unable to quit smoking or relapse to smoking without the aid of pharmacologic therapy for smoking cessation. Currently, there are two types of pharmacologic therapies (Nicotine Replacement Therapy and Sustained-release bupropion) that are FDA approved for smoking cessation in the U.S. To date, there has been no clinical trial comparing use of the nicotine patch and sustained-release bupropion, alone or in combination, as pharmacologic therapy for smoking cessation among low income, younger participants or in minority participants. Given the high relapse rates among these groups in general, the combination of nicotine replacement therapy and sustained-release bupropion may be particularly efficacious. Therefore, we hypothesize that use of a combination of the nicotine patch and sustained-release bupropion as compared to use of the nicotine patch alone or to sustained-release bupropion alone will result in increased initial and long term rates of smoking cessation in younger low income and minority persons who smoke. We plan to test these hypotheses in this double blind clinical trial by randomizing younger, low income and minority persons who smoke to one of three groups: Group 1) Nicotine patch plus placebo sustained-release bupropion, Group 2) Sustained-release bupropion plus placebo nicotine patch, or Group 3) Nicotine patch plus sustained-release bupropion. Our primary endpoint assessment is smoking cessation rates by self-report verified by biochemical validation at different time points between the three treatment groups. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ACUTE NICOTINE ABSTINENCE IN ADOLESCENTS Principal Investigator & Institution: Krishnan-Sarin, Suchitra; Assistant Professor; Psychiatry; Yale University 47 College Street, Suite 203 New Haven, CT 065208047 Timing: Fiscal Year 2001; Project Start 30-SEP-1998; Project End 31-MAY-2003 Summary: The applicants will conduct a detailed, prospective examination of tobacco withdrawal symptoms of male and female adolescents who are either heavy users, light users or nonusers of tobacco products (including cigarettes and smokeless tobacco). In adults, physical dependence as documented by the presence of withdrawal symptoms, is known to be an important factor in the maintenance of cigarette smoking, and the intensity of nicotine withdrawal has been shown to be directly correlated to the intensity of nicotine use. It has been suggested that like adults, adolescents may also be
14 Nicotine
physically dependent on nicotine. However, all the studies examining incidence of nicotine withdrawal in adolescents have been retrospective in nature, but they suggest that self-reports from adolescents indicate that they also experience withdrawal during abstinence from nicotine. The specific aims of this proposal are (1) to conduct a prospective and systematic study of nicotine withdrawal symptomatology in adolescents who differ in amount of tobacco use (heavy users, light users, nonusers) using standard nicotine withdrawal measures as well as the Clinical Institute for Narcotic Assessment (CINA) scale-(2) to evaluate gender differences in the incidence of nicotine withdrawal in adolescents, (3) to determine if adolescents experience cognitive performance deficits during nicotine withdrawal and if these deficits are greater in heavy users compared with light users of tobacco products, (4) to evaluate alterations in responsivity to both physical and mental stress during nicotine withdrawal, in heavy and light users of tobacco products, compared with nonusers of tobacco and (5) to document alterations in responsivity of the hypothalamo-pituitary-adrenal (HPA) axis and sympathetic system during nicotine withdrawal and exposure to stress. The results of this study would have substantial implications for the use of nicotine substitution and other treatments in adolescents for the pharmacological management of withdrawal, and could also help elucidate the role of cognitive deficits and stress in maintaining cigarette smoking in adolescents. Determining physical dependence and related changes in adolescent tobacco users may also provide valuable information regarding the process of development and maintenance of nicotine dependence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ADDRESSING NICOTINE ADDICTION IN DRUG ABUSE PATIENTS Principal Investigator & Institution: Richter, Kimber; Psychology and Sociology; University of Kansas Medical Center Msn 1039 Kansas City, KS 66160 Timing: Fiscal Year 2001; Project Start 05-FEB-2000; Project End 31-JAN-2005 Summary: Kimber P. Richter, Ph.D., M.P.H., is a behavioral psychologist with training in public health who will use the MRSDA to develop expertise in addressing nicotine addiction among persons in drug abuse treatment, an estimated 80 percent of whom smoke. The proposal combines her behavioral background in drug abuse prevention, drug abuse treatment, and cardiovascular disease risk reduction with a new focus on smoking cessation. This plan outlines the training and research experience she will need, over the next 5 years, to develop and launch a fully independent career addressing nicotine addiction among persons in drug abuse treatment. Career Development: Activities include training in the chemistry of the nervous system, advanced biostatistics, training in addictions treatment and research, a week-long internship with a nicotine/drug addictions researcher, and an intensive bioethics course. Research Program: The goal of the proposed research program is to better understand smoking behaviors and nicotine dependence among persons in treatment for chemical dependencies, and to identify acceptable and potentially effective methods for reducing cigarette smoking in this population. Specifically, the plan involves three studies that address five research questions. Study 1 examines key issues in smoking cessation from the patient's point of view. It consists of a series of two focus groups among each of four subgroups of clients in methadone maintenance treatment (MMT) and other drug dependency programs. These 8 sessions is will identify clients' a) interest in quitting, b) barriers to quitting smoking, c) successful strategies used to quit smoking, d) strategies used to avoid illicit drug use that might be adapted for smoking cessation, and e) treatment preferences for quitting smoking. Study 2 is a descriptive study examining interactions in patterns of cigarette use and methadone maintenance. Twenty-one
Studies 15
methadone patients will use electronic monitors to record the frequency and timing of their cigarette consumption. Data on methadone timing and dose, as well as carbon monoxide levels and psychological measures of nicotine craving and withdrawal, will be collected and analyzed to assess whether methadone dose and timing are associated with surges in cigarette consumption and smoking urges. Study 3 is a pilot study examining the feasibility and potential efficacy of a multicomponent intervention on smoking cessation. Sixty MMT patients will be randomly assigned to treatment (nicotine inhaler and motivational interviewing) or control (placebo inhaler and comparable staff contact). Primary outcomes include quit rates and avg. daily cigarette use. Pilot data will allow determination of sample sizes for a full-scale intervention trial, and will be used to assess the effects of variables such as age, gender, methadone dose on treatment effects. The research plan uses exploratory, descriptive, and intervention research to address fundamental issues of nicotine addiction. Each study stands on its own, but is designed to build on the findings of the prior study. This research may serve as a model for systematic research on nicotine addiction in patients with other drugs of dependence or who are in other drug abuse treatment modes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ADOLESCENT PROGRESSION OF NICTOINE DEPENDENCE Principal Investigator & Institution: Niaura, Raymond S.; Director of Research; Miriam Hospital Providence, RI 02906 Timing: Fiscal Year 2001 Summary: (Applicant's Description) Little is known about individual differences in susceptibility to nicotine dependence among youth. While most adolescents experiment with tobacco, the majority do not go on to develop a pattern of habitual use and nicotine dependence. While both familial and biobehavioral factors are important in predicting cigarette use, little is known about; 1) the familial aggregation of smoking especially among adolescents and first degree relatives (parents and siblings); 2) the nicotine use and dependence phenotypes which are transmitted from parent to child; and 3) heritable biobehavioral substrates which may predispose toward nicotine dependence. Characteristics related to disruptive behavior disorders (e.g., attention deficit hyperactivity disorder, conduct disorder) and mood disorders (e.g. depression) are associated with smoking in both youth and adults. Maternal smoking during pregnancy increases the likelihood of youth smoking and young adult nicotine dependence, and is simultaneously associated with a variety of developmental and neurocognitive deficits (e.g., ADHD; conduct disorder) that may increase the likelihood of developing nicotine dependence by potentiating the reinforcing effects of nicotine. The aims of this proposal are to study associations between: (1) Adolescent comorbid disruptive behavioral disorders, mood disorders, and the progression of nicotine dependence; (2) Corresponding parental and sibling comorbid smoking, nicotine dependence, antisocial, ADHD, and mood disorders in relation to adolescents' progression of nicotine dependence; and (3) Effects of maternal smoking during pregnancy on incidence and trajectory of comorbid disruptive behavioral and mood disorders and nicotine dependence. Accordingly, 644 families (adolescents, siblings and parents) will be studied prospectively over 3 years to determine those factors which predict progression of nicotine dependence. This prospective family study will utilize both existing and new data gathered as part of the National Collaborative Perinatal Project (NCPP), whose New England cohort includes over 16,000 adults who have been followed since birth, whose early neurological, cognitive, and psychological functioning has been documented, and whose children are, on average, 14 years old, and will be 17 years old
16 Nicotine
when the proposed study is complete. We propose to study comorbid disruptive behavioral and mood disorders in these children, their parents and siblings, and use this information to predict progression of nicotine dependence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REPLACEMENT
ALCOHOL
SELF-ADMINISTRATION/EFFECT/NICOTINE
Principal Investigator & Institution: Mckee, Sherry; Psychiatry; Yale University 47 College Street, Suite 203 New Haven, CT 065208047 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2004 Summary: (provided by applicant): It is well established that alcohol use and smoking behavior are highly correlated, particularly for individuals who are moderate to heavy drinkers, as compared to light drinkers. In general, smokers are more likely to drink regularly and consume larger quantities of alcohol than nonsmokers and drinkers are much more likely to smoke. However, much is still unknown concerning the interaction of the two substances. Human laboratory studies examining interactions of nicotine and fixed-doses of alcohol have demonstrated alterations in craving, subjective intoxication, and mood. Investigations have yet to examine the effect of nicotine, administered by transdermal nicotine patch, on reactivity to alcohol. Prior studies have examined nicotine nasal spray and nicotine gum on reactivity to a fixed-dose of alcohol but is possible that the pharmacokinetics and blood nicotine levels achieved by transdermal patch may alter findings produced by other routes of administration. Additionally, research has yet to examine the effect of transdermal nicotine replacement on alcohol self-administration behavior. Given that transdermal nicotine replacement is the most commonly used nicotine replacement strategy, it effects on alcohol reactivity is an important area of investigation. Using an alcohol self-administration paradigm developed by our group, the primary aim of this project is to examine whether transdermal nicotine replacement (21 mg/day), as compared to mild nicotine withdrawal (0mg placebo patch), alters reactivity to alcohol following exposure to a priming drink and subsequent ad-libitum drinking in individuals who are moderate to heavy drinkers. Specifically we will examine whether nicotine replacement reduces 1) ad-libitum alcohol consumption, 2) alcohol craving, 3) subjective intoxication, and 4) mood. A secondary aim is to examine whether transdermal nicotine replacement decreases the ability of alcohol to prime tobacco craving. This study will have important implications for alcohol-nicotine interactions, smoking cessation in alcohol drinkers, and alcohol challenge studies in general. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ALPHA CONOTOXIN MII--SELECTIVE NICOTINIC RECEPTOR PROBE Principal Investigator & Institution: Marks, Michael J.; Research Associate; Inst of Behavioral Genetics; University of Colorado at Boulder Boulder, CO 80309 Timing: Fiscal Year 2002; Project Start 01-FEB-1999; Project End 30-JUN-2007 Summary: (provided by applicant): Nicotine elicits behavioral effects through a diverse family of nicotinic acetyicholine receptors (nAChR) and nicotine evoked dopamine release is thought to play an important role in the establishment and maintenance of nicotine dependence. a-ConotoxinMll (aCtxMII), a toxin isolated from the predatory cone snail Conus magus, potently and selectively blocks a3b2-nAChR expressed in Xenopus oocytes and partially inhibits nicotine-stimulated dopamine release from rat
Studies 17
striatal synaptosomes. During the initial funding period for this grant aCtxMII has been used to identify subsets of nAChRs in mouse brain. It was confirmed that aCtxMII inhibits some, but not all, nicotine-stimulated dopamine release in mouse striatum. As expected, b2 null mutants retained virtually no aCtxMII binding or nicotine-stimulated release. Surprisingly, the b3 null mutation eliminated most high affinity aCtxMII binding and aCtxMII-sensitive dopamine release. Equally surprising was the absence of an effect of the a3 null mutation on aCtxMII binding. Therefore, many native nAChRs that interact with aCtxMII are not the a3b2 subtype. Experiments outlined in the current proposal will use ligand binding and functional analyses to further examine the diversity of nAChR. 1) aCtxMII sensitivity of nAChR mediated dopamine release in striatum, nucleus accumbens, frontal cortex and olfactory tubercles of mice that have been mutated to eliminate the expression of specific nAChR subunits (initially a7, a5, b2, b3 and b4) will be evaluated to obtain information about the molecular composition and functional diversity of these important presynaptic nAChRs. 2) Regulation of nAChR binding and function by chronic nicotine treatment using both wild type and null mutant mice, with emphasis on those mutants that affect nAChRs that interact with aCtxMII, will also be examined. 3) Structural properties of the recently identified aCtxPWl, which differs markedly in structure from aCtxMII, but displays a similar pharmacological profile, will be evaluated to determine if this new toxin will prove to be superior or complementary reagent. The proposed studies will provide further insights into the nature of three novel, native nAChRs sensitive to inhibition by aCtxMII and may lead to better understanding of the basis of the effects of nicotine Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANIMAL MODELS OF NICOTINE SUSCEPTIBILITY Principal Investigator & Institution: Leslie, Frances M.; Professor; University of California Irvine Campus Dr Irvine, CA 92697 Timing: Fiscal Year 2001 Summary: The majority of adult smokers initiate smoking as children. Most previous studies of the biological effects of nicotine have focused on adults rather on adolescence, a developmental period that is characterized by sexual maturation and by significant changes in brain structure and function. In the present proposal we will use animal models to examine the biological factors that underlie susceptibility to nicotine. In particular, we will test the following hypotheses: (l) That the balance of reinforcing/aversive effects of nicotine is greater in juveniles than in adults. (2) That individual differences in susceptibility to nicotine dependence are associated with variations in stress responsivity. Three specific aims are proposed. First, the effects of nicotine will be compared in juvenile rats aged postnatal day (p) 30 and in adults. Animals will be treated with nicotine and tested behaviorally. At the end Of some experiments animals will be decapitated and trunk blood collected for the measurement of corticosterone levels. Brains will be processed by in situ hybridization for quantitative analysis of the expression of mRNA for the immediate early gene, cfos, in specific neuronal populations. Experiments will be conducted with both male and female rats to determine whether nicotine is more reinforcing in juveniles than adults using both conditioned place preference and self adrnistration paradigms. Animals will also be tested to determine whether conditioned sensitization to the locomotor activating effects of nicotine Occurs more rapidly in juveniles than adults, and to determine whether juvenile exposure to nicotine increases sensitivity to nicotine in adults. Second, individual differences in stress responsivity will be induced by a procedure in which pups are either handled (H) or not handled (NH) for two weeks after birth. H and NH
18 Nicotine
groups will then be compared as juveniles and adults to determine whether differences in stress responsivity result in different acute effects of nicotine on locomotion, plasma corticosterone and cfos expression. Differences in the reinforcing effects of nicotine in H and NH groups will also be examined, as will differences in withdrawal severity following chronic nicotine treatment. Third, the effects of nicotine on genetically distinct strains of mice will be studied. Both acute and chronic effects of nicotine in C3H andC57B1/6J mice, and in transgenic mice with alterations in selected genes, will be examined. These studies will provide critical information on the biological mechanisms underlying individual variations in responsivity to nicotine and will complement the human studies in projects I and 2. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANIMAL MODELS OF RISK FACTORS FOR RELAPSE TO SMOKING Principal Investigator & Institution: Picciotto, Marina R.; Associate Professor; Yale University 47 College Street, Suite 203 New Haven, CT 065208047 Timing: Fiscal Year 2001 Summary: As the overall number of smokers in the American population decreases, many of those that continue to smoke show several risk factors that make smoking cessation more difficult. Some of these risk factors may be environmental while others may have a genetic component. We propose to study the biological basis underlying how risk factors might lead to relapse to smoking. Some major predictors of treatment failure for smoking cessation include depressive symptoms, heavy alcohol use, and female gender. This proposal will use animal models to determine how nicotine affects biological processes related to these risk factors, and will focus on how activation or inhibition of neuronal nicotinic acetylcholine receptors (nAChRs) can affect behavioral and biochemical responses related to these risk factors. These experiments will make use of pharmacological studies in normal mice as well as experiments with transgenic (knock-out) mice lacking the beta2 subunit of the nAChR which have previously been generated. Existing nicotinic agonists cannot distinguish clearly between the various nicotinic subtypes present in the brain; thus these mice will be extremely useful in identifying which receptor subtypes mediate particular pharmacological actions of nicotine. The aims of this project are to determine whether nicotine can act as an antidepressant in the learned helplessness model of depression, to determine whether nicotine withdrawal increases susceptibility to learned helplessness during acute and chronic abstinence, to identify sex- differences in learned helplessness behavior with and without nicotine treatment, to determine the concurrent and independent effects of chronic ethanol and nicotine treatment on biochemical and behavioral responses to stress, and to determine whether chronic nicotine treatment results in changes in levels of second messenger proteins involved in signaling that are associated with motivation and effect. The techniques to be used include neurochemistry, molecular genetics and behavioral paradigms. These approaches should allow an integrated view of how chronic nicotine use and nicotine cessation affect emotional behavior, and how gender differences or alcohol use can modulate that interaction. These experiments will contribute to the scientific background necessary for designing new strategies for treatment of smokers resistant to current cessation methods. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BEH DEPENDENCE
PHARM
TREATMENTS
FOR
ALCOHOL/NICOTINE
Principal Investigator & Institution: Schmitz, Joy M.; Professor; Psychiatry and Behavioral Scis; University of Texas Hlth Sci Ctr Houston Box 20036 Houston, TX 77225 Timing: Fiscal Year 2001; Project Start 01-SEP-1998; Project End 31-MAY-2003 Summary: APPLICANT'S ABSTRACT: Alcohol abuse and dependence and nicotine dependence are major health problems in the U.S. Each is exacerbated when used together. Combined pharmacotherapies may offer promising new directions for treating dually-dependent patients. Specifically, transdermal nicotine replacement (TNR) and naltrexone (NTX) have significant clinical utility for the treatment of smoking and alcoholism, respectively. These medications, when used simultaneously, may facilitate smoking cessation during alcohol treatment. Such medication effects would be optimized in the context of adjuvant psychotherapeutic interventions, particularly those emphasizing relapse prevention (RP) skills training. It is our contention, that the concurrent application of TNR and NTX has a definite role within the context of nicotine-alcohol treatment and that there is a pressing need for a prospective clinical trial. The proposed double-blind, placebo controlled, 2x2 factorial study will determine the potential interactions between the two treatments by crossing alcohol treatment (NTX 50mg/d vs. placebo) with smoking treatment (active TNR vs. placebo). Both pharmacotherapies will be applied within a context of a cognitive-behavioral RP skills training therapy that emphasizes the linkage between smoking and drinking. Alcoholnicotine dependent subjects (n=200) will be randomly assigned to one of four outpatient treatment conditions, then begin the 12-week trial involving weekly clinic visits. Smoking status will be based on self-report, expired air carbon monoxide and saliva cotinine levels. Alcohol consumption will be measured by self-report, breath alcohol readings, collateral reports, and liver function tests. Primary efficacy parameters for drinking and smoking will include time to lapse/relapse and cumulative absence duration. Secondary efficacy measures will include alcohol and smoking consumption, clinical global impression, retention in treatment, ASI scores, and medication compliance. We predict that subjects receiving TNR and NTX as adjuncts to RP will have higher rates of abstinence from both substances than subjects who do not receive these pharmacologic adjuncts. Secondary aims of this study will include: 1) assess the influences of process variables (coping, self-efficacy, craving, depression) on treatment outcome; 2) test the prognostic significance of patient variables (nicotine/alcohol dependence, readiness to change, stress, depression), as well as explore potential patient-treatment matching effects; 3) evaluate the maintenance of treatment gains over a 6-month follow-up period. The results will advance our understanding of clinical research issues related to the concurrent treatment of alcohol and nicotine in duallydependent patients. Finally, the proposed study will continue and extend the scope of our ongoing research program designed to evaluate the joint effects of behavioral and pharmacological interventions for substance dependence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BEHAVIORAL AND NEUROCHEMICAL EFFECTS OF PULSED NICOTINE Principal Investigator & Institution: Koeltzow, Timothy E.; Psychiatry; University of Chicago 5801 S Ellis Ave Chicago, IL 60637 Timing: Fiscal Year 2001; Project Start 01-SEP-2001
20 Nicotine
Summary: (provided by applicant): Nicotine dependence is thought to underlie the profound public health problems associated with tobacco use. Although nicotine?s effects on the mesoaccumbens DA system likely account for the reinforcing effects of nicotine, it is also known that chronic nicotine exposure produces robust functional tolerance, an effect that may significantly increase the aversive impact of abstinence. The relative contribution of these factors to the maintenance of compulsive tobacco use remains unclear. Animal studies indicate that the temporal pattern of nicotine administration may be a critical factor in the development of certain neural adaptations associated with chronic nicotine exposure. Although this concept is particularly important given the highly regular rates of daily tobacco use exhibited by most smokers, it is unknown how different patterns of nicotine administration influence the ability of this drug to engage the mesoaccumbens DA system. The present proposal is designed to determine how different temporal patterns (continuous, pulsed, or intermittent) of intravenous nicotine administration influence the development of tolerance and/or sensitization. The first aim will determine whether different patterns of identical cumulative nicotine doses will influence the ability of nicotine to stimulate extracellular DA concentrations in the nucleus accumbens. The second aim will assess the effects of different patterns of nicotine administration on subsequent acquisition and maintenance of operant nicotine self-administration. We hypothesized that pulsed nicotine administration will elicit adaptations of the mesoaccumbens DN system distinct from those associated with continuous or intermittent protocols to significantly impact subsequent self-administration behavior. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BEHAVIORAL EFFECTS OF NICOTINE IN NACHR MUANT MICE Principal Investigator & Institution: Paylor, Richard E.; Assistant Professor; Baylor College of Medicine 1 Baylor Plaza Houston, TX 77030 Timing: Fiscal Year 2001 Summary: Understanding how neuronal nicotinic acetylcholine (nAChRs) regulate central nervous system (CNS) function will depend on the identification of particular roles for specific receptor subunits. Existing data indicate that certain subtypes of nicotinic receptors contribute to different behavioral effects of nicotine. For example, the effect of nicotine on exploratory activity appears to be regulated by receptor subtypes that bind nicotine with high affinity, while the effects of nicotine on sensorimotor gating and nicotine induced-seizures are regulated by receptors that bind alphabungarotoxin. Similar relationships exist between the development of tolerance to nicotine and increases in the different nicotinic receptor subtypes. This project will test the hypothesis that the different nicotinic receptor subunits regulate the sensitivity to nicotine and the development of nicotine tolerance. The firs aim of the project will examine the role of individual nAChR subunits in regulating normal baseline behavioral responses. N Nicotine affects numerous behavioral responses in mice and rats including activity, motor coordination, anxiety, sensorimotor gating, and analgesic-related responses. The second aim will evaluate the effects of nicotine on a wide array of behavioral assays to determine if different nicotinic receptors regulate different behavioral effects of nicotine. For these studies dose response curves will be generated for the effects of nicotine in alpha7-, alpha5-, alpha4-, beta2-, or beta4-deficient mice on open-field activity, several assays of anxiety, rotarod performance, prepulse inhibition, and the hot-plate test. Nicotine also improves learning and memory performance. our third aim of this project will determine if the alpha7 or beta2 subunits, which are known to be expressed in the hippocampus, regulate the effects of nicotine on hippocampal-
Studies 21
dependent learning and memory performance. The final aim will investigate the role of alpha7 and beta2 subunits in the development of nicotine tolerance to several behavioral effects of nicotine following chronic nicotine infusions. The findings from these studies will provide insight into the functional role of different nAChR subunits in nicotine addiction and dependence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BEHAVIORAL GENETICS OF NICOTINE DEPENDENCE Principal Investigator & Institution: Sirevaag, Erik J.; Research Assistant Professor; Psychiatry; Washington University Lindell and Skinker Blvd St. Louis, MO 63130 Timing: Fiscal Year 2001; Project Start 05-AUG-2001; Project End 30-MAY-2006 Summary: This proposed project, which is submitted by a new investigator, will examine genetic influences on biological responses to nicotine in women using a pharmacogenetic paradigm. Specifically, this project will: (i) determine whether there are substantial genetic influences upon reactivity to nicotine in non-smokers, and (ii) examine the relationship between level of reactivity, progression to regular smoking and risk for dependence. Genetic influences upon nicotine reactivity will be determined within the context of a laboratory nicotine challenge protocol which will provide subjective, physiological and performance-based measures of nicotine responsivity in twin pairs stratified by smoking status. Monozygotic (MZ) and dizygotic (DZ) correlations in twin pairs concordant for non-smoking will be used to estimate the contributions of genes, shared environment and within-family environmental differences in experience to variability in measures of nicotine reactivity. Twin pairs can also be observed in smokers. The relationship between nicotine reactivity and risk for dependence will be evaluated by estimating the correlations, stratified by zygosity, of the responses to nicotine in non-smoking twins drawn from smoking-discordant twin pairs with the level of dependence evidenced by the smoking co-twin. Dependence will be defines as score on the modified Fagerstrom FTND Dependence scale. To enhance statistical power, same-sex full siblings of smoking twins will also be tested whenever available. Previous epidemiological studies have indicated that at least some factors influencing smoking dependence appear to be substantially heritable. Data obtained from the proposed project may facilitate the elucidation of critical (phenotypic) differences in biological responses to nicotine. These results could subsequently be used to inform future studies examining the genetics of smoking dependence and persistence and may also impact the development of appropriately targeted smoking prevention and cessation interventions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BEHAVIORAL IMPACT OF NICOTINE WITHDRAWAL Principal Investigator & Institution: Besheer, Joyce; Psychology; University of Nebraska Lincoln 14Th and R Sts Lincoln, NE 68588 Timing: Fiscal Year 2001; Project Start 01-OCT-2001; Project End 31-MAY-2002 Summary: Chronic tobacco use continues to be a worldwide public health problem. Presently, there is an emphasis on smoking cessation which is prompting the development of new pharmacotherapies and treatment programs. Unfortunately, relapse after a brief period of smoking cessation is common. Most people attribute the relapse to the occurrence of withdrawal symptoms. Examination of behavioral and neurochemical changes that occur during nicotine withdrawal will help provide insight into nicotine relapse. Better understanding of these processes will result in the
22 Nicotine
development of more effective cessation and prevention programs. The experiments in the present proposal seek to examine the effects of nicotine withdrawal on two behavioral preparations widely used in our laboratory. The first preparation assesses place preference conditioned by access to novel objects (i.e., novelty reward). Rats receive repeated access to novel object in one environment and no objects in another equally experienced environment. In a post-conditioning test that occurs in the absence of any objects, rats show a preference for the environment previously paired with novel. The second preparation assesses preference for a novel object over a familiar object (i.e., novelty seeking). In this task rats are presented with an object for a specific amount of time. The rats are returned to the environment 1 h later, but now have free-access to a novel object and the previously experienced object. During this novel- object test rats spend more time interacting with the novel object than the familiar object. Based on related research and theory, we predict that nicotine withdrawal will affect rats' response to novelty as assessed by these tasks. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BEHAVIORAL VULNERABILITY TO EARLY SMOKING RELAPSE Principal Investigator & Institution: Brown, Richard A.; Associate Professor; Butler Hospital (Providence, Ri) 345 Blackstone Blvd Providence, RI 02906 Timing: Fiscal Year 2001; Project Start 01-SEP-2000; Project End 31-AUG-2003 Summary: Relapse continues to plague public health efforts to reduce the prevalence of cigarette smoking. Recent evidence suggests that a large percentage of individuals attempting smoking cessation lapse to smoking within a matter of days, and few recover to achieve and maintain smoking abstinence. Results of studies relating severity of nicotine withdrawal symptoms to short-term smoking cessation outcomes have been equivocal. Instead of focusing on severity of withdrawal symptoms, we suggest that factors surrounding how one reacts to symptoms of nicotine withdrawal is more promising. In total, biological, physiological, emotional and behavioral responses to nicotine withdrawal constitute a type of biobehavioral reactivity that may convey vulnerability to early smoking lapse, and in a broader sense, may be an important component of dependence to nicotine. The overall aim of this study is to examine biobehavioral mechanisms related to early smoking lapse in a laboratory investigation of 84 cigarette smokers making an unaided smoking cessation attempt. The sample will be stratified by gender, level of nicotine dependence and history of major depression. Additionally, subjects will be followed for four weeks after attempting cessation, and based upon a median split of time to first smoking lapse, will be grouped as either early lapsers or sustainers. Prior to self-quitting, subjects will be exposed to three laboratory procedures to investigate biobehavioral reactivity to (a) a psychological stressor, (b) physical discomfort and (c) a neuroendocrine dexamethasone/corticotropin releasing hormone (DEX/CRH) challenge test. We expect that early lapsers will have higher levels of reactivity to these procedures on biological, physiological, affective and behavioral measures. Secondarily, we hypothesize that these biobehavioral measures of reactivity will be related to lifetime recurrent MDD, elevated measures of affective vulnerability, and elevated negative mood upon initial cessation. We expect that the results of this study will increase our basic knowledge about biobehavioral vulnerability factors in early smoking lapse and subsequent relapse in smokers quitting without professional assistance, a group that is understudied yet accounts for 90 percent of all cigarette smokers. Because early lapsers represent a recalcitrant group of smokers who are at-risk for continued nicotine dependence, these research findings should hold considerable
Studies 23
clinical and public health significance and may result in the development of novel pharmacological and cognitive- behavioral treatments for nicotine dependence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BIOBEHAVIORAL DEPENDENCE
ASPECTS
OF
ADOLESCENT
NICOTINE
Principal Investigator & Institution: Wood, Teresa L.; Adult Health and Illness; Ohio State University 1800 Cannon Dr, Rm 1210 Columbus, OH 43210 Timing: Fiscal Year 2001; Project Start 15-NOV-2000 Summary: Adolescent smoking prevalence has continued to climb with 1997 estimates being the highest reported since 1979. The relationship between adolescent smoking and subsequent nicotine dependence in adulthood has been well established. While biological effects of smoking have been studied in adults, the biobehavioral aspects have not been examined in adolescents. In addition gender differences in smoking that have been reported for adolescents address sociobehavioral factors with limited emphasis on biological data which is essential for understanding adolescent nicotine dependence. The need to identify biomarkers of adolescent nicotine dependence is essential to the health of adolescent smokers. The first aim of this one-factor factorial design study is to characterize the biomarkers of smoke constituent exposure and smoking topography parameters in adolescent smokers. Smoke constituent exposure includes carbon monoxide and plasma nicotine increases post-cigarette and baseline cotinine levels. Smoking topography parameters include puff volume and duration, interpuff interval, and inhalation and exhalation duration. In the second aim smoking topography parameters, smoke constituent exposure, and level of nicotine dependence will be compared between adolescent male and female smokers. The third aim will compare smoke constituent exposure, smoking topography parameters and level of nicotine dependence of prepubescent and later teens. The final aim will contrast biological markers of smoke constituent exposure with accepted behavioral measures of nicotine dependence. Characterizing biological and behavioral aspects of smoking in adolescent boys and girls will provide a foundation to address the gap in this important research area. The proposed study represents the first phase of a program of research that includes analyzing differences in smoking behavior of adolescents from multiple ethnic groups, as well as increasing the scientific basis from which to design tailored smoking prevention and cessation interventions by gender and age group. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ADDICTION
BIOBEHAVIORAL
MARKERS
OF
RISK
FOR
NICOTINE
Principal Investigator & Institution: Anokhin, Andrey P.; Assistant Professor; Psychiatry; Washington University Lindell and Skinker Blvd St. Louis, MO 63130 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 30-JUN-2006 Summary: (Applicant's Abstract) This Mentored Research Scientist Development award (KO1) resubmission requests 5 years of support for research and advanced research training on the genetic and biobehavioral etiology of substance use disorders, using nicotine addiction as a model system. Although a strong genetic contribution to smoking behavior has been well documented by recent studies, little is known about biobehavioral mechanisms that might mediate increased genetic risk. The overall goal of the proposed research is to identify electrophysiological trait markers of genetic susceptibility to nicotine addiction and to differentiate them from the long-term impact
24 Nicotine
of smoking on brain function. This goal will be achieved through the integration of genetic and experimental psychophysiological methods. Epidemiological and behavioral research strongly implicates disinhibition (deficits of inhibitory selfregulation of behavior) as a potential mediator of susceptibility to smoking and other substance use behaviors. The proposed study will use an extended co-twin control design to delineate genetic and environmental causes of differences between smokers and nonsmokers on psychophysiological traits pertinent to disinhibition. Young adult MZ female twins and their siblings (total n=300) concordant and discordant for lifetime regular smoking will be recruited from an ongoing study of 3000 female twins and their parents. Assessments will include a diagnostic interview, questionnaires, and a battery of laboratory psychophysiological tests. The focus will be on electrophysiological traits theoretically and empirically linked to cognitive and behavioral disinhibition: ERPs elicited in classical oddball and Go-No Go tasks and prepulse inhibition of startle response (PPI). Specific aims are to identify genetically transmitted characteristics of CNS functioning indicative of increased vulnerability to nicotine addiction and to assess the long-term impact of smoking on brain function. Significantly elevated MZ compared to full sib correlations will lead to a future ROI proposal to study DZ pairs, to confirm genetic etiology. It is expected that the proposed study will advance our understanding of biobehavioral mechanisms mediating vulnerability to nicotine addiction and provide useful end phenotypes for future genetic linkage or association studies of smoking and other substance use disorders. The training component will include supervised research, formal course work and tutorials in advanced methods of genetic analysis, and lab training in experimental psychopharmacology. The acquired expertise will allow the candidate to better integrate genetic and psychophysiological approaches in order to establish a program of interdisciplinary research in the neurobehavioral genetics of addiction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BIOBEHAVIORAL NICOTINE DEPENDENCE IN BLACK WOMEN Principal Investigator & Institution: Ahijevych, Karen L.; Adult Health and Illness; Ohio State University 1800 Cannon Dr, Rm 1210 Columbus, OH 43210 Timing: Fiscal Year 2001; Project Start 01-FEB-1997; Project End 31-JAN-2004 Summary: (Applicant's Abstract) More African Americans die from diseases caused by cigarette smoking than from AIDS, homicide, drugs and accidents combined. In addition, smoking intensifies a number of serious health problems that disproportionately affect African Americans including heart disease, cancer, stroke, low birth weight, and infant mortality. African Americans report smoking fewer cigarettes per day, prefer high nicotine, mentholated brands, and are noted to be highly dependent on nicotine. Higher cotinine levels, the major metabolite of nicotine, have been described in black women, in comparison to other race-gender groups, in spite of smoking fewer cigarettes per day. Furthermore, there is a lower smoking cessation quit rate among African American women compared to Caucasian women. Alternative explanations for increased exposure as indicated by elevated cotinine levels in African American women are warranted. The overall aim of the FIRST award proposal is to examine effects of selected biobehavioral and contextual factors on smoke constituent exposure and nicotine dependence in African American and Caucasian women. Three separate studies to be conducted in the General Clinical Research Center (GCRC) with black and white women are proposed. 1) To characterize cotinine elimination trends, subjects will be admitted for a 7-day inpatient study of smoking abstinence during which plasma cotinine levels will be obtained. The effect of race, body composition, and
Studies 25
menthol preference on cotinine trends will be analyzed. 2) During a 4 hr study, the effects of smoking topography (e.g. puff duration and volume and lung retention time), race, menthol preference, and body composition on plasma nicotine trends postcigarette will be analyzed. Menthol exposure will be examined. 3) During a 6-day inpatient study with a counterbalanced design, smoke constituent exposure as measured by plasma nicotine and carbon monoxide increases pre to post-cigarette, as well as puff duration and volume, and lung retention time, will be contrasted across three conditions of nicotine availability of usual, increased and restricted smoking rates. Information about metabolic and behavioral issues concerning nicotine will add to a limited knowledge base about nicotine dependence in African American women and provide scientific support for specific targeted smoking cessation interventions, in conjunction with or separate from nicotine replacement. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BRAIN REWARD SYSTEM, DEPRESSION AND NICOTINE DEPENDENCE Principal Investigator & Institution: Busto, Usoa E.; Center for Addiction and Mental Health 250 College St Toronto, Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 30-JUN-2004 Summary: (provided by applicant) There is a high comorbidity between nicotine dependence and major depressive disorder (MDD). Smokers with comorbid MDD are more likely to become dependent on nicotine, more severely dependent, and experience more serious withdrawal symptoms than smokers without MDD. MDD also has a negative impact on the outcome of smoking cessation treatments. The neurobiological mechanisms of nicotine dependence and comorbid MDD are unknown. We propose to assess the activity of the brain reward system (BRS) as a possible neurobiological link between MDD and nicotine dependence. Although many neurotransmitters are involved in the pathophysiology of these two disorders, we propose that: 1) A dysfunctional dopaminergic BRS may be responsible for some mechanisms involved in nicotine dependence and MDD; and 2) Smoking may modulate the activity of the BRS by enhancing dopaminergic activity relieving some depressive symptoms (e.g., anxiety). We propose two human experimental studies. Study I will a) assess the activity of the BRS by measuring the effects of a single oraF dose of d-amphetamine (d-amph) in depressed (DSM IV diagnosed, not on antidepressants, n=20) and non-depressed smokers (n=20); b) determine whether nicotine modifies the response to d-amph; and c) determine whether nicotine withdrawal symptoms are different during smoking and non-smoking conditions. We will measure physiological and rewarding effects of damph using valid self-report instruments at baseline and 30, 60, 120, 180, and 240 min post-drug. Plasma levels of damph and homovanillic acid will be measured. Study 2 will use PET to measure dopamine-medialed ['C] Raclopride displacement before and after 30mg of d-amph in 24 control and 24 MDD (12 smokers and 12 nonsmokers/group) subjects. It will also determine whether the rewarding effects of damph correlate with ['C] Raclopride displacement. Results may provide evidence for neurobiological mechanism (s) explaining the high comorbidity between MDD and nicotine dependence. The BRS could become the target for developing new treatments for nicotine dependence and some symptoms of MDD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
26 Nicotine
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Project Title: BRAINSTEM NACHR SUBTYPES & THEIR EFFECT ON GI FUNCTION Principal Investigator & Institution: Gillis, Richard A.; Pharmacology; Georgetown University Washington, DC 20057 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (provided by applicant): Administration of nicotine and/or smoking has been shown to have important effects on gastric function. Evidence of others and our own data strongly indicate that these effects are due to nicotine acting on neuronal nicotinic acetylcholine receptors (nAChRs) in the dorsal motor nucleus of the vagus (DMV) and medial subnucleus of the tractus solitarius (mNTS). The goals of our proposed studies are to: (i) investigate the influence of DMV and mNTS nAChRs in the effects of systemically administered nicotine on gastric function and (ii) to use DMV and mNTS nAChRs as model systems to learn more about native CNS nicotinic receptors, their nature, their function and their regulation. The Specific Aims of our research are to: (i) determine the subunit composition of nAChRs in the rat DMV and mNTS that mediate the effects of nicotine on gastric tone and motility; (ii) examine regulation of the function and density of nAChRs in rat DMV and mNTS after chronic administration of nAChR-stimulating doses of nicotine, and the agonist-induced responsiveness of nAChRs in the DMV and mNTS after acute exposure to sub-activating doses of nicotine; and (iii) test the hypothesis that nAChRs observed to exist in the DMV and mNTS as revealed by pursuing Specific Aims 1 & 2 play an important role in the gastric effects (DMV and mNTS) and cardiovascular effects (mNTS) of systemically administered nicotine. To achieve these Specific Aims, a focused but multidisciplinary approach will be used consisting of the following techniques: (i) pharmacological tools applied either in vivo by microinjection of drugs into the DMV and mNTS of anesthetized rats while monitoring gastric tone and motility, or in vitro to rat brain slice preparations containing the DMV and mNTS while monitoring electrophysiological events using the whole-cell patch-clamp recording method; (ii) in vitro autoradiography taking advantage of the high affinity epibatidine binding to nAChRs combined with selective denervation of efferent and afferent vagal fibers; (iii) immunofluorescent identification of nAChR subtypes in DMV and mNTS neurons; (v) fluorescent in situ hybridization technique to identify nAChR subunits associated with DMV neurons projecting to the fundus and antrum, (vi) knockout mice, in which one gene of interest is silenced, and the contribution of a particular nAChR subunit (e.g., a7 subunit) in eliciting a specific gastric response can be assessed. Findings made to date suggest that: (I) there are five different nAChRs in the DMV and mNTS that influence gastric function; (ii) there might be a viscerotopic organization of nAChR subunits on DMV motoneurons. That is a7 containing nAChRs might be located primarily on DMV neurons projecting to the fundus but not on DMV neurons projecting to the antrum; and (iii) iv. administered nicotine might act in the mNTS on a ct4B2-nAChR subtype to inhibit tonic contraction of the fundus. These and future data obtained from pursuing our Specific Aims will extend current understanding of the different receptor mediated effects of nicotine on parasympathetic nervous system control of the upper GI tract. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BUPROPION AS AN ADJUNCT TO THE NICOTINE PATCH PLUS CBT Principal Investigator & Institution: Fava, Maurizio; Director, Depression Clinical & Res. Pro; Massachusetts General Hospital 55 Fruit St Boston, MA 02114 Timing: Fiscal Year 2001; Project Start 01-JAN-1999; Project End 31-DEC-2003
Studies 27
Summary: We are proposing a five-year, double-blind, placebo-controlled trial on the smoking cessation efficacy of bupropion as an adjunct to the standard combination of group cognitive-behavioral therapy (CBT) plus nicotine replacement. Our primary aims are 1) to examine the additional benefit of adding the antidepressant bupropion to a standard treatment for smoking cessation of CBT and nicotine replacement among smokers who have a history of either current or past unipolar depressive disorders (major depressive disorder, dysthymia, and minor depression), and 2) to determine, if bupropion indeed improves in this population a smoker's odds of quitting, whether its effect is achieved mainly through its impact on the negative mood states associated with depression. In order to provide a powerful test of both hypotheses, this study will enroll only smokers with a history of either current or past unipolar depressive disorders. In addition, allowing the inclusion of patients with a history of unipolar depressive disorders makes the proposed study more clinically relevant and its findings more generalizable, as several studies suggest that, as the prevalence of smoking continues to diminish in the general population, an increasing percentage of those who remain smokers are patients with psychiatric illnesses, especially depression. We expect that the efficacy of the standard combination of group CBT plus nicotine replacement will be greatly enhanced by the addition of bupropion in all smokers, but that the addition of bupropion will be especially helpful to those smokers who currently suffer from clinically significant depressive symptoms. The study involves the enrollment over 48 months of 300 individuals. We predict that 50 percent of the enrolled patients will meet criteria for current unipolar depressive disorders. After the 12-week acute treatment phase, patients will be followed for 12 months. The study design therefore involves the random assignment of current or past history of unipolar depressed patients to two treatment conditions: 1) group CBT plus nicotine patch plus bupropion (current depressive disorder bupropion group, estimated n=75; past depressive disorder bupropion group, estimated n=75); 2) group CBT plus nicotine patch plus placebo (current depressive disorder placebo group, estimated n=75; past depressive disorder placebo group, estimated n=75). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BUPROPION TREATMENT FOR YOUTH SMOKING CESSATION Principal Investigator & Institution: Muramoto, Myra; Assistant Professor; None; University of Arizona P O Box 3308 Tucson, AZ 857223308 Timing: Fiscal Year 2001; Project Start 30-SEP-1997; Project End 31-JUL-2003 Summary: (Applicant's Description) Tobacco use remains the leading preventable cause of premature death in the U.S., and this public health problem will remain so if advances in the treatment of nicotine dependence do not occur. While the approved medications for smoking cessation to date are those that provide nicotine replacement, recent studies evaluating the effects of novel non-nicotine medications suggest that significant improvements in cessation rates may be possible. One of the most promising non-nicotine medications is bupropion (Zyban). Bupropion has been available as an antidepressant that increases dopamine availability and thus elevates mood, and will be FDA approved as a smoking cessation medication. Furthermore, it has been investigated as a medication for the treatment of attention deficit/hyperactivity disorder in youth. Because the efficacy of bupropion for adult smoking cessation is greater than nicotine replacement, and because the safety of bupropion has been shown in youth, it is the clear choice for investigation as a pharmacologic treatment for youth smoking cessation. Since the optimal dose for smoking cessation has not been assessed in youth, a dose ranging study to evaluate the safety and efficacy of bupropion for smoking cessation in
28 Nicotine
youth is proposed. The proposed study is a randomized, double-blind, placebocontrolled clinical trial designed to assess (1) which bupropion dose, if any, increases abstinence rates over placebo, and (2) which factors, such as medication adherence, nicotine dependence, and motivation to quit, affect treatment outcome. There are a number of potential benefits from the proposed study. The results of the proposed study could lead to a better understanding of how to use a pharmacologic treatment for youth smoking cessation. Initiation of tobacco use is largely a sociocultural process, nicotine dependence is a medical condition whose treatment is optimized when the full armamentarium of medical care is provided. The proposed study will follow Agency for Health Care Policy and Research guidelines for smoking cessation, including a medical model approach that combines behavioral and pharmacologic intervention within a health care environment. While many studies have evaluated cessation methods for adults, there remains a dearth of research evaluating methods for enhancing youth smoking cessation. With so little research upon which to expand, the proposed study could lead to important new understandings regarding the process and mechanisms of youth smoking cessation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RECEPTORS
CALCIUM
SIGNALING
BY
HIPPOCAMPAL
NICOTINIC
Principal Investigator & Institution: Vijayaraghavan, Sukumar; Assistant Professor; Physiology; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, CO 800450508 Timing: Fiscal Year 2002; Project Start 15-JAN-1998; Project End 31-MAR-2007 Summary: (provided by applicant): Nicotine is a habit-forming drug that is widely used in our society. The widespread distribution of nicotinic acetylcholine receptors (nAChRs) in the brain suggests that the dynamics of nicotine use in humans is likely to be complex. Understanding mechanisms underlying the action of nicotine in the CNS must begin with the elucidation of the function of various brain nAChR subtypes. Our findings that hippocampal astrocytes express functional nAChRs suggest that these receptors might play a role in astrocytic signaling and that some of the actions of nicotine might be mediated by astrocytes. We propose to examine the spread of nAChR-activated calcium signals in stellate hippocampal astrocytes in culture, using fluorescence imaging techniques. The ability of nAChRs to cause release of glutamate consistent with vesicular exocytosis will be examined using HEK 293 cells transfected with NMDA receptors, combined with whole cell voltage-clamp measurements. The presence of nAChRs on astrocytes in situ will be determined by whole cell voltageclamp measurements from astrocytes in hippocampal slices from GFAP/GFP transgenic mice. nAChR-mediated calcium signaling will be examined using fura 2 AM loaded astrocytes in hippocampal slices from the GFAP/GFP mice. The possibility that nicotine-induced modulation of glutamatergic miniature excitatory currents (mepscs) is due to amplification of signals from store calcium release will be examined using electrophysiological techniques in hippocampal slices. A potential role for astrocytic nAChRs in the regulation of synaptic activity will be examined using hippocampal neurons cultured in the presence and absence of astrocytes. Results from this project will demonstrate mechanisms by which nAChRs on astrocytes could alter hippocampal function specifically and neuronal signaling in general and also suggest a role for astrocytic nAChRs in mediating the effects of nicotine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
Studies 29
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Project Title: TOLERANCE
CALCIUM-DEPENDENT
MECHANISMS
IN
NICOTINE'S
Principal Investigator & Institution: Damaj, M. Imad.; Associate Professor; Pharmacology and Toxicology; Virginia Commonwealth University Richmond, VA 232980568 Timing: Fiscal Year 2001; Project Start 01-FEB-2001; Project End 31-JAN-2004 Summary: The broad objective of this proposal is to elucidate the calcium- dependent mechanisms of nicotinic receptor function. It was recently shown that neuronal nicotinic receptors (nAChRs) have a high Ca2+ permeability and our initial studies indicate that changes in calcium homeostasis and Ca2+/calmodulin-dependent protein kinase (CaMKinase II) can modulate nicOtine's pharmacological effects and are involved in neuroadaptative processes after chronic exposure to nicotine in the animal. In this project we plan to study calcium-dependent intracellular mechanisms and their modulation after short and long-term activation of nAChRs. We will assess the potential role of CaM-kinase II activatiOn in the behavioral effects of nicOtine using pharmacological, biochemical and genetic approaches. Tolerance to nicotine's effects could involve an adaptation in the calcium signaling system activated by nicotine leading to a decrease in in CaM-kinase II activity. Such a hypothesis will be investigated by measuring quantitative and qualitative changes in Ca2+-calmodulin-dependent signaling in in vitro and ex-vivo preparations during long-term exposure to nicotine. Finally, we will attempt to modulate tolerance to nicotine's effects by administering drugs that alter calcium entry. In vivo studies with calcium channel modulators and CaM-Kinase II inhibitors as well as NMDA receptor antagonists will be conducted in animals chronically infused with nicotine. The proposed studies will elucidate the calcium-dependent processes involved in nicotine's actions in the brain as well as the neuroadaptation that occurs after short-and long-term exposure to this drug of abuse. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ADDICTION
CELLULAR
AND
MOLECULAR
ASPECTS
OF
NICOTINE
Principal Investigator & Institution: Dani, John; Professor; Neuroscience; Baylor College of Medicine 1 Baylor Plaza Houston, TX 77030 Timing: Fiscal Year 2001; Project Start 15-JAN-1997; Project End 30-NOV-2001 Summary: (Applicant's Abstract) In the United States, tobacco use causes 400,000 deaths a year, making it the leading cause of premature death. Although multiple psychopharmacological effects contribute to tobacco abuse, nicotine is accepted as the primary component that reinforces the habit. Nicotine binds to nicotinic acetylcholine receptors (nAChRs). The rate of nicotine delivery and the time of exposure dictates how the populations of nAChRs distributes among functional states that are closed, ion conducting, desensitized, or long term inactivated. Smokers take in a small pulse of nicotine with each cigarette. These peaks of nicotine ride on a maintained low level of nicotine that increases with repeated cigarettes during the day. The research will test the following hypothesis: The pulse of nicotine could activate nAChRs that evoke dopamine release and produce "rewarding" effects mediated mainly via the mesolimbic dopaminergic system. The sustained low levels of nicotine, however, could cause significant desensitization or longer-term inactivation of nAChRs that may underlie tolerance or aspects of withdrawal symptoms mediated by non-reward pathways. Patch-clamp electrophysiology, calcium measurements, and immunocytochemistry will be used to investigate the hypothesis. Microexplants of ventral tegmental area (VTA)
30 Nicotine
neurons synapsing onto low density cultures of nucleus accumbens neurons will be examined to determine how nicotine evokes dopamine release. VTA brain slices and tissue cultures of VTA and habenula neurons will be used to understand the time scales and effects of nAChR desensitization and long-term inactivation as well as recovery from those states. Nicotinic AChR activation, leading to DA release by mesolimbic neurons, may provide the reinforcing reward that initiates tobacco abuse. A further drive to smoke may arise because smokers are medicating themselves with nicotine on longer time scales to control the degree to nAChR desensitization and inactivation that may underlie aspects of tolerance and withdrawal symptoms. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHARACTERIZATION OF NICOTINE RECEPTORS Principal Investigator & Institution: Martin, Billy R.; Louis/Ruth Harris Professor and Chair; Virginia Commonwealth University Richmond, VA 232980568 Timing: Fiscal Year 2001; Project Start 30-SEP-1988; Project End 30-JUN-2006 Summary: Nicotine produces diverse pharmacological effects after acute administration, and we have shown recently that profound dependence occurs after repetitive exposure. Pharmacological evidence, coupled with molecular biology, has revealed multiple neuronal nicotinic receptor subtypes in brain, and the definitive functional role for these receptor subtypes is slowing emerging. In order to continue establishing the functional role of these receptor subtypes, we will continue to pursue our structure-activity relationship studies that are providing intriguing leads for developing more receptor selective agonists and antagonists. Moreover, these probes are providing a means for assessing structural requirements for activation of the receptor. Analogs will be evaluate for receptor selectivity and efficacy using receptor binding, a battery of in vivo pharmacological effects, and in vitro functional assays. The synthetic analogs that we will be examining have sufficient structural diversity to allow redefinition of the pharmacophore for nicotine receptors. In addition to understanding nicotine's acute actions, we propose to investigate the mechanism by which nicotine produces dependence. We recently developed a dependence model using chronic nicotine infusion in mice. This model will allow us to determine which receptor subtypes are involved in dependence. These studies will consist of substituting receptor selective agonists for nicotine as well as participating withdrawal with receptor selective antagonists. Chronic infusion in nicotine in receptor knock-out mice will confirm the involvement of specific receptor subtypes in nicotine dependence. Moreover, we propose to distinguish between the contributions of peripheral and central nicotine receptors in the development of dependence. Finally, our observations that bupropion has both nicotine agonist and antagonist properties represents an important lead for further exploration of the mechanisms underlying the pharmacological effects of nicotine and the development of dependence. To further investigate the antagonistic effect of bupropion, a number of bupropion analogs as well as its metabolites will be evaluated for antagonism of nicotine effects. Finally, bupropion will be evaluated in mice chronically infused with nicotine to determine whether it alleviates or exacerbates withdrawal. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CHOLINERGIC REINFORCEMENT
AND
OPIATE
MECHANISMS
IN
DRUG
Principal Investigator & Institution: Corrigall, William A.; Director; Center for Addiction and Mental Health 250 College St Toronto,
Studies 31
Timing: Fiscal Year 2001; Project Start 01-APR-1997; Project End 31-JAN-2003 Summary: (Adapted from the Investigator's Abstract) Discovery of the central nervous system mechanisms by which drugs influence behavior is important in understanding the basic processes in brain and behavior in general, and more practically because it establishes the knowledge base for the development of medications to treat dependence, as well as identifying potential substrates for biological variability. Studies of the reinforcing effects of drugs have identified that a particular population of dopamine neurons located in the ventral part of the midbrain (ventral tegmental area, VTA) play a major role in drug-taking behavior. However, these dopamine systems are not uniquely involved in drug-taking behavior, but also subserve other motivated behaviors and motor functions. The approach taken in this research is to discover other neuronal systems which likely regulate these dopamine neurons and hence influence drug-taking behavior. Our hypothesis has two parts. First, we propose that the activation of mu opioid receptors in the VTA can have different effects on the self-administration of nonopioid drugs like nicotine and cocaine, depending on the extent of recruitment of GABAergic elements in the VTA by the drug in question. Second, we propose that cholinergic projections from the mesopontine area to the VTA play a role in drug reinforcement when they are activated. This preclinical research uses techniques in which animals are trained to do work (press a lever) to obtain intravenous infusions of nicotine or cocaine. Brain pathways and mechanisms are identified by manipulating the drug-taking behavior with neurochemical lesions of particular neuronal pathways in the brain, or by microinfusions of neurochemicals into certain brain areas. Conceptually the experiments proposed to test the first part of the hypothesis build on the observation that the focal administration of a mu-selective opioid agonist into the VTA alters cocaine self-administration more than nicotine self-administration. Experiments in this application will test whether this observation reflects an effect on the ability of the selfadministered drug to reinforce behavior, and whether GABAergic mechanisms are involved. The second part of our hypothesis derives from studies which have shown that selective lesions of the cholinergic cells of the caudal part of the pedunculopontine tegmental nucleus (PPTg), which provide cholinergic input to the VTA, or blocking the effects of nicotine in the PPTg with a nicotinic antagonist, reduce nicotine selfadministration. Experiments will examine whether depleting this population of cholinergic cells produces a selective effect on nicotine versus cocaine reinforcement, and whether agents that alter the activity of these cholinergic cells affect reinforcement more generally. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CYTOKINES
CHOLINERGIC
MODULATION
OF
INFLAMMATORY
CNS
Principal Investigator & Institution: Gahring, Lorise C.; Associate Professor; Human Molecular Biology/Genet; University of Utah 200 S University St Salt Lake City, UT 84112 Timing: Fiscal Year 2003; Project Start 15-FEB-2003; Project End 31-DEC-2006 Summary: (provided by applicant): We are examining mechanisms of neuronal-glial interactions within the context of how a proinflammatory cytokines and the nicotinic cholinergic neurotransmitter systems interact to determine neuronal susceptibility to excitotoxins in a neuroinflammatory environment, as is often present in neurological disease. The Overall Hypothesis is: Pre-exposure of CNS cells to the cholinergic agonist, nicotine, modifies signaling initiated by TNF alpha and alters neuronal vulnerability to excitotoxins and the CNS response during neuro-inflammatory processes. This
32 Nicotine
hypothesis stems from several key results that include: 1. Cultured cortical neurons are protected against an NMDA-toxic challenge by TNFalpha or nicotine, however, TNF alpha and nicotine induced neuroprotection is abolished when the agents are present together cultures of mixed neurons and glia, 2. These agents are not antagonistic in enriched neuronal cultures suggesting that other non-neuronal cell types are required, 3. The addition of mononuclear phagocytes/microglial cells (MP/MG) to enriched neuronal cultures restores antagonism between nicotine and TNFalpha. 4. MP/MG in culture express nAChRs, and they respond functionally to the presence of nicotine, and 5. Nicotine administration alters the kinetics of TNFalpha-initiated caspase 8 activation, an important intracellular mediator of TNFalpha-signaling. We will determine in Specific Aim 1 if nicotine/TNFalpha antagonism of neuroprotection to NMDA requires specific cell-cell interactions between cells of the CNS including neurons and MP/MG, In Specific Aim 2 if neuronal nicotinic receptors, in addition to nAChRalpha7, and expressed by cell types other than neurons, participate in mechanism(s) related to nicotine/TNFalpha antagonism of neuroprotection and in Specific Aim 3 if nicotine preconditioning of CNS cells alters their response to TNFalpha through modifying caspase/protease activation and/or function. These studies have direct and novel implications toward understanding the consequences of sustained nicotine presence on the normal regulation of neuro-inflammation in the CNS, which may determine susceptibility to many toxins and influence normal and pathological responses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHRONIC NICOTINE ON RECEPTOR REGULATION OF SERT ACTIVITY Principal Investigator & Institution: Awtry, Tammy L.; Pharmacology; George Washington University 2121 I St Nw Washington, DC 20052 Timing: Fiscal Year 2001; Project Start 25-SEP-2001 Summary: (provided by the applicant) In this application, novel models are proposed to characterize 5-HT3 receptor regulation and trafficking of the serotonin transporter (SERT) in hippocampus and prefrontal cortex (PFC) and to determine how chronic nicotine use affects this regulation. SERT is primarily responsible for the termination of synaptic 5-HT activity by re-uptake and it is the therapeutic target for several disorders including depression. The hippocampus and PFC are brain regions critical in cognition learning and memory and nicotine has been shown to enhance these processes. 5-HT3 agonists enhance amphetamine stimulated release of serotonin (5-HT) in PFC but not in the hippocampus. The ability of 5-HT3 receptors to alter SERT trafficking will be modeled and studied in HEK-293 cells transfected with 5-HT3 receptors and SERT. Chronic nicotine treatment changes the responsiveness of the SERT to regulation by 5HT3 receptors in hippocampus; after chronic nicotine treatment, 5-HT3 agonists are now able to enhance amphetamine stimulated 5-HT release. Models are proposed to determine how chronic nicotine use affects serotonergic systems. A superfusion system will be used to characterize 5-HT3 receptor-mediated regulation of 5-HT release via the SERT. Binding experiments and in situ hybridizations will be performed to determine how chronic nicotine affects 5-HT3 receptor and SERT expression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: COCAINE/NICOTINE ACTION ON ACETYLCHOLINE RECEPTORS Principal Investigator & Institution: Oswald, Robert E.; Professor; Molecular Medicine; Cornell University Ithaca Office of Sponsored Programs Ithaca, NY 14853
Studies 33
Timing: Fiscal Year 2002; Project Start 15-MAY-1998; Project End 31-MAR-2007 Summary: (provided by applicant): The goal of this project is to determine the molecular mechanism by which two abused drugs, nicotine and cocaine, interact with neuronal nicotinic acetyicholine receptors (nAChRs) in the peripheral and central nervous systems. Cocaine exerts its euphoric, addictive nature through the dopamine transport system, but some of its toxic effects are mediated by subtypes of neuronal nAChRs. nAChRs regulate signal transmission between many central nervous system neurons and at the neuromuscular junction, and both nicotine and cocaine affect their function. Reports in the literature have suggested that cocaine and other local anesthetics, when administered intraventricularly, are antagonistic to the behavioral and pharmacological effects of nicotine. We have identified RNA sequences (RNA aptamers) that interact with nAChRs and can alleviate the effects of cocaine without affecting receptor function. Likewise, several cocaine derivatives have been identified with similar properties. One aim of this proposal is to extend these studies to a variety of neuronal nAChR subtypes in order to develop specific agents that will alleviate the effects of cocaine and the inhibitory effects of (-)nicotine. The second group of studies will build on our previous work indicating that the effects of cocaine are mediated by at least two sites which differ among neuronal nAChR subtypes. Stably transfected cell lines and a newly developed transfection system will be used to study the transient kinetics of various subtypes of neuronal nAChRs in order to characterize in more detail the binding sites for cocaine and nicotine. Rapid mixing techniques and laser-pulse photolysis will be used to provide temporal resolution on the muS to ms timescale. The molecular mechanism, including knowledge of the concentration at which nicotine and cocaine affect specific nAChRs, will provide a basis for mechanism-based design of therapeutic agents that alleviate some effects of the drugs without themselves having deleterious effects. The knowledge gained is expected to contribute to the rational treatment of the millions of individuals adversely affected by cocaine and nicotine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COMBINATION NICOTINE REPLACEMENT FOR ALCOHOLIC SMOKERS Principal Investigator & Institution: Cooney, Ned L.; Psychiatry; Yale University 47 College Street, Suite 203 New Haven, CT 065208047 Timing: Fiscal Year 2002; Project Start 01-AUG-1997; Project End 31-JUL-2006 Summary: (provided by applicant): This is a competitive renewal of a grant entitled "Field Study of Smoking Cessation in Alcohol Treatment." Tobacco use among alcoholics is a major public health problem. The broad objective of this study is to develop recommendations for empirically supported smoking cessation treatment for alcoholic smokers in the initial phase of outpatient alcoholism treatment. In a double blind, placebo controlled clinical trial; a sample of 175 alcohol dependent cigarette smokers will be recruited from the community and treated in a six month outpatient alcohol and tobacco treatment protocol. All subjects will be offered a total of 15 individual treatment sessions with a goal of abstinence from alcohol and tobacco. They will also be randomized to one of two levels of nicotine replacement therapy (NRT). One group will receive Combination INRT consisting of active nicotine patch and active nicotine gum, while a comparison group will receive Single NRT consisting of active nicotine patch and placebo nicotine gum. Smoking and drinking outcome will be assessed across one year from the onset of treatment. In addition to the outcome assessment, Ecological Momentary Assessment (EMA) methodology will be used to examine treatment process. EMA data will be collected using cellular telephones
34 Nicotine
combined with Interactive Voice Response technology to randomly sample each subject's experience in the natural environment during two week periods before smoking cessation, immediately after smoking cessation, and two months after smoking cessation. This methodology will be used (a) to compare the overall effects of Single versus Combination NRT on frequency and intensity of urge to smoke and urge to drink; (b) to determine the immediate impact of nicotine gwn self administration on subsequent momentary urge to drink and urge to smoke; and (e) to determine the momentary effect of urges to drink and urges to smoke on subsequent nicotine gum self administration. The results of these process analyses will lead to improved understanding of the effects of nicotine replacement on alcoholic smokers and factors affecting their compliance with nicotine gum. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COMBINING A SMOKE ENDING AID WITH BEHAVIORAL TREATMENT Principal Investigator & Institution: Gariti, Peter; Psychiatry; University of Pennsylvania 3451 Walnut Street Philadelphia, PA 19104 Timing: Fiscal Year 2001; Project Start 01-MAY-1999; Project End 30-APR-2002 Summary: No single smoking cessation treatment has emerged as effective for all smokers. Although there has been a decline in the number of smokers, most remaining smokers, despite a professed desire to quit, have been unsuccessful in their efforts to do so. While various nicotine replacement products have shown promise as safe, effective adjunctive aids for dealing with the effects of withdrawal from nicotine, relapse rates are quite high once treatment is terminated. There is a great need for other cost effective and optimal treatment strategies for reducing this high relapse rate. Based on encouraging preliminary findings the use of a non-pharmacological agent, Accu Drop, plus brief motivational enhanced counseling may provide a novel set of conditions to potentially offer an optimal multi-modal smoking cessation treatment strategy to a wide range of smokers who are willing to undertake an active effort to address their smoking problem. Accu Drop is a corn syrup based food additive which is purported to trap nicotine and tar when applied to the filter of cigarettes. At the maximum dose, smoking machines have demonstrated a 88 percent-98 percent reduction in nicotine delivery. The proposed research is the first study to test the efficacy of the Accu Drop solution in combination with multimodal behavioral treatment. The 20-30 minute counseling sessions emphasize applying the drops as prescribed as well as creating an individualized schedule and plan of action for reducing cigarette usage leading toward total smoking cessation and maintenance by the end of treatment. The first objective of this proposed Innovative Stage 1B Behavioral Therapy Development Research project is to finalize a treatment manual for the counseling sessions that are provided in conjunction with Accu Drop use. A second objective of the research is to more fully systematize therapist training procedures for this treatment as well as quality assurance procedures to ensure treatment integrity. The final research objective is to conduct a preliminary study under randomized, double-blind, placebo controlled conditions, to evaluate the efficacy of a 6 week Accu Drop nicotine fading protocol used in conjunction with cigarette tapering to bring about termination of cigarette usage in moderate to heavy smokers (greater than or equal to 15 cpd) who are interested in smoking cessation. Both the experimental and control groups in this study will receive six weeks of the manually driven behavioral treatment by experienced and trained therapists. The experimental group (N=30) will also be prescribed active Accu Drops (AD and C) while the control condition (N=30) will be prescribed placebo Accu Drops
Studies 35
(PD and C) very similar in appearance, viscosity, and taste to active Accu Drops. Completion of the study protocol and smoking cessation rates at 1 week, 1 month, and 6 months post-treatment will be the prime measures of efficacy. The findings of this study will provide sufficient evidence for the efficacy of the experimental treatment and its extended investigation in a Phase II study or for its nonefficacy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COMPUTERIZED SCHEDULING OF NICOTINE INHALER USE Principal Investigator & Institution: Riley, William T.; Director of Research; Personal Improvement Computer Systems 12007 Sunrise Valley Dr, Ste 480 Reston, VA 22091 Timing: Fiscal Year 2001; Project Start 30-JAN-1999; Project End 30-APR-2002 Summary: The overall goal of this Phase II project is to assess the efficacy of a computerassisted program to schedule nicotine inhaler dosing for smoking cessation. The product, LifeSign for Nicotine Inhalers, will be refined based on information obtained from the Phase I trial. Efficacy will be evaluated by comparing two computer-assisted nicotine inhaler dosing and reduction schedules, fast-paced (LS-NI-F) and slow-paced (LS-NI-S), versus ad libitum nicotine inhaler use (AL-NI). Subjects (N=480) will be evaluated on various smoking-related measures at pre-treatment and at 9 and 21 week follow-ups. Subjects also will complete weekly smoking and inhaler logs and data from the computer units will be uploaded for analysis of inhaler use. A brief one- year followup also will be performed. The results of the study will provide useful information on the effects of computer-assisted scheduling and duration of use of nicotine inhalers as well as patterns of ad libitum inhaler use. PROPOSED COMMERCIAL APPLICATIONS: The proposed product will have broad commercial appeal to all smokers who want to quit via nicotine inhalers. For health care professionals who often have inadequate time to provide adjunct behavioral treatment for patients using nicotine inhalers, this product will provide a simple and effective adjunct. Pharmaceutical companies have expressed interest in collaborative marketing arrangements. When nicotine inhalers becomes available over-the- counter, the product will have provide consumers with a way to assure adequate dosing and appropriate taper of inhaler use. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CORE--BIOMARKER LABORATORY Principal Investigator & Institution: Hecht, Stephen S.; Wallin Professor; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, MN 554552070 Timing: Fiscal Year 2001 Summary: The Biomarker Core provides a unique resource to the TTURC investigators. This Core will provide not only biomarker measurements, but also expertise in the interpretation of these data and their application in the design of further research approaches toward reduction of tobacco associated diseases. The work of this Core is highly integrated into all projects of the TTURC. The expertise of this Core in tobacco carcinogenesis, nicotine biochemistry, and carcinogen metabolism adds an important dimension to this TTURC. The work of the Biomarker Core will center around two main broad themes: 1) measurement of nicotine metabolites and biomarkers of carcinogen uptake to assess the relationship of tobacco exposure at various levels to uptake of nicotine and carcinogens and 2) the relationship of nicotine metabolism, as mediated by cytochrome P450 2A6, to susceptibility to cigarette use. The following alkaloids, metabolites, and adducts will be quantified in this work: nicotine metabolites including
36 Nicotine
nicotine-glucuronide, cotinine, cotinine-glucuronide, trans~3?~ hydroxycotinine, and trans-3'-hydroxycotinine-glucuronide; 7- hydroxycoumarin as a measure of cytochrome P450 2A6 activity; 4- (methylnitrosamino)-l-(3-pyridyl)-l-butanol (NNAL) and its glucuronide (NNAL-Gluc) as measures of uptake of the tobacco-specific lung carcinogen 4-(methylnitrosarnino)-I-(3-pyridyl)-l-butanone (NNK); I- hydroxypyrene as a measure of uptake of carcinogenic polycyclic aromatic hydrocarbons; 4aminobiphenyl-hemoglobin adducts as indicators of the uptake and metabolic activation of the human bladder carcinogen 4- aminobiphenyl; F2-isoprostanes as indicators of oxidative damage associated with cigarette smoking; and metabolites of NNK as influenced by nicotine administration. Collectively, these biomarkers will substantially enhance our understanding of the biochemical and mechanistic aspects of the tobacco exposure reduction strategies being explored in this TTURC. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CORE--GENETICS EPIDEMIOLOGY Principal Investigator & Institution: Merikangas, Kathleen R.; Professor; Miriam Hospital Providence, RI 02906 Timing: Fiscal Year 2001 Summary: (Applicant's Description) The major goal of the Genetic Epidemiology Core is to provide the conceptual basis and methodology to investigate the role of environmental and genetic risk factors and their joint contribution to the development of nicotine dependence. Limitations in our basic knowledge regarding the recurrence risk of tobacco dependence in families, patterns of familial aggregation of tobacco dependence, as well as the extent to which wholly environmental factors may induce this phenotype render any attempt to identify susceptibility genes premature. To date, there is not a single published controlled family study of nicotine-related phenotypes using contemporary family study methodology. Identifying the role of susceptibility genes underlying complex phenotypes such as tobacco use require basic knowledge in several disciplines including epidemiology, behavior genetics, molecular genetics, statistical genetics, and population genetics. Progress achieved in each of these areas specifically deviated to enhancing our understanding of the phenotype and genotypes of relevance to nicotine dependence will enable us to develop a comprehensive conceptualization of the influence of genetic factors at each stage of the development of tobacco dependence. Even without the identification of specific genes, the genetic epidemiology perspective provides a powerful approach to integrate familial and individual risk factors that influence nicotine use, and may lead to the identification of targets for prevention. The specific goals of our core will be to: (1) centralize assessment of family history, accurate collection of pedigree information, and ethnicity; (2) examine a wealth of existing data available from study investigators across the entire center to refine phenotypic definitions and identify sources of complexity of the familial aggregation of smoking; (3) develop and apply analytic methods on patterns of familial aggregation and the environmental contexts of nicotine outcomes in the core resource of community based probands and families that form the central basis for this center; (4) conduct basic research on candidate genes for nicotine dependence and statistical models for family-based association studies that reflect the complexity of this phenotype in preparation for identifying genes in the core data from the present application; and (5) provide training for center investigators and trainees in the concepts and methods of genetic epidemiology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
Studies 37
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Project Title: CUE REACTIVITY IN DUAL ALCOHOL AND NICOTINE ADDICTION Principal Investigator & Institution: Drobes, David J.; Associate Professor; Psychiatry and Behavioral Scis; Medical University of South Carolina 171 Ashley Ave Charleston, SC 29425 Timing: Fiscal Year 2001; Project Start 01-FEB-1998; Project End 31-JAN-2003 Summary: It has been well documented that there is a high rate of co-morbidity between alcoholism and nicotine dependence. Increasing evidence supports an important role for conditioning mechanisms in both forms of addictive behavior. Specifically, alcoholics and smokers tend to display certain patterns of responding when confronted with environmental and interoceptive stimuli that have been reliably associated with previous drug taking. This phenomenon is often termed cue reactivity, and several theoretical models have been forwarded to account for this reactivity. Given the high rate of smoking among alcoholics, it is conceivable that smoking cues or nicotine withdrawal may promote cravings for alcohol. The failure to account for this relationship in alcohol treatment may be counterproductive and may lead to an increased risk for relapse. The proposed research will examine patterns of cue reactivity among alcoholics who are currently addicted to nicotine, as well as comparison groups of alcohol-only, nicotine-only, and non-dependent controls. Study 1 will entail development and empirical validation of a set of alcohol-relevant imagery scripts that will be used, in combination with previously developed smoking- relevant imagery scripts and visual cues for alcohol and nicotine, in two subsequent cue reactivity studies. In Study 2, these imaginal and visual cues will be presented during separate phases of a cue reactivity assessment, along with standardized pleasant, neutral, and unpleasant cues as affective controls. Reactivity will be indexed across three general responses domains (i.e., verbal report, psychophysiological, and behavioral), and will include assessment of the startle eye blink reflex and a measure related to information processing models of cue reactivity (i.e., reaction time). In Study 3, all subjects will be nicotine-dependent alcoholics, and the assessment will occur during one of the three levels of nicotine withdrawal for separate groups of subjects. The results should improve our understanding of the strong association between nicotine and alcohol addiction, and will have implications for the treatment of this dual addiction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CYTOCHROME METABOLISM
P450
POLYMORPHISM
AND
NICOTINE
Principal Investigator & Institution: Ring, Huijun Z.; Sri International 333 Ravenswood Ave Menlo Park, CA 94025 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2005 Summary: (provided by applicant): This is an R03 application from a new investigator. The goal of this research is to identify the genes and basic mechanisms that are associated with nicotine dependence in humans. Converging evidence suggests that genetic variations in the rate of metabolism of nicotine can play a role in mediating nicotine dependence. The family of CYP450 enzymes, including CYP2A6, CYP2B6 and CYP2D6, play a pivotal role in nicotine metabolism. While genetic variation in the CYP2A6 gene has been shown to affect nicotine metabolism and alter an individuals' smoking behavior, the effects of genetic variation in CYP2B6 and CYP2D6 on nicotine metabolism and dependence remain to be elucidated. Thus, in the research outlined in this application, we will assess whether there is a correlation between CYP2B6 and/or
38 Nicotine
CYP2D6 genotypes and specific nicotine pharmacokinetic parameters. We will concentrate on four specific phenotypes, which have shown the highest heritabilities in previous in vivo nicotine pharmacokinetics studies: (i) nicotine and cotinine half-life, (ii) nicotine clearance, (iii) cotinine volume of distribution and (iv) rate constant marking CYP450 activity. We will also evaluate whether the CYP2B6 and CYP2D6 genotypes modulate the effect of the CYP2A6 genotype on nicotine pharmaeokinctic parameters and will estimate the proportion of the variation in nicotine metabolism that is explained by each of these three genes and by any gene-gene interactions between them. Dr. Huijun Ring, along with Drs. Neal Benowitz, Gary Swan, Rachel Tyndale and Ana Valdes, form a strong multi-disciplinary research team that uniquely qualifies them to carry out the proposed research. The proposed research will be the first to completely characterize the genotypes of all three nicotine C-oxidase genes and to study their relative roles in in vivo nicotine metabolism. This project is an important pilot study to explore the relationship between CYP450 polymorphisms and nicotine metabolism, and we intend to follow it up with future studies that have larger sample size in order to test for more nicotine addiction related phenotypes. This systematic genetic approach will help to identify genetic mechanisms that underlie individual susceptibility to nicotine dependence and provide new insights into the etiology of smoking and will facilitate the development of new intervention and preventive strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DA RELEASE IN THE NACC IN A NICOTINE SELF-ADMIN MODEL Principal Investigator & Institution: Kane, Victoria G.; Pharmacology; University of Tennessee Health Sci Ctr Health Science Center Memphis, TN 38163 Timing: Fiscal Year 2001; Project Start 01-MAR-2001 Summary: (provided by applicant) The vast human toll and financial burden that tobacco places on society is no longer in question, yet effective treatments for smoking cessation are still unavailable. Nicotine has been found to be one of the primary reinforcing agents in tobacco. There remain many unanswered questions about the physiological correlates of nicotine administration. The current proposal seeks to investigate the relationship between dopamine (Da) release in the nucleus accumbens (NAcc), a site commonly associated with reward, and operant conditioning, and nicotine self-administration (SA). The specific aims of the proposal are (1) to determine the effects of nicotine on Da release within the mesolimbic system, specifically in projections from the ventral tegmental area (VTA) to the NAcc shell, using a novel approach that combines in vivo microdialysis with a 24-hour unlimited access selfadministration (SA) model, and (2) to investigate the effects on Da in the Nacc shell when a reward is strengthened (via varying the dose of nicotine) and also the contingency of the reward is altered (via changing the FR schedule). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DEVELOPMEMT OF NOVEL TREATMENTS FOR NICOTINE ADDICTION Principal Investigator & Institution: Dwoskin, Linda P.; Professor; Pharmaceutical Sciences; University of Kentucky 109 Kinkead Hall Lexington, KY 40506 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 30-JUN-2008 Summary: (provided by applicant): Tobacco smoking is the number one health problem accounting for more illnesses and deaths in the US than any other factor. Despite efficacy of some current pharmacotherapies (i.e., nicotine replacement and bupropion),
Studies 39
relapse rates continue to be high, indicating that novel medications are needed. Research in the current application proposes to develop a new class of subtype-selective nicotinic receptor (nAChR) antagonists as therapeutic agents with efficacy for tobacco use cessation and for treatment of nicotine dependence. As much as tobacco use behavior and nicotine addiction have links to depression, these novel drug candidates may also prove to be new treatments for depression. Based on the observations that the bupropion acts as a nAChR antagonist and that the nonselective nAChR antagonist, mecamylamine, has some efficacy as a tobacco use cessation agent, but is limited by its peripherally-mediated side-effect of constipation, we predict that the subtype-selective nAChR antagonists, which we propose to develop, may have therapeutic advantages and efficacy as tobacco use cessation agents in the treatment of nicotine addiction. We hypothesize that quaternizing the pyridine-N atom of the nicotine molecule with a lipophillic N-substituent to afford N-nicotinium analogs and/or by connecting these quaternary ammonium moieties with a lipophillic linker to afford N,N'-bis-analogs will result in subtype-selective nAChR antagonists, which will inhibit either nicotine-evoked dopamine, norepinephrine or serotonin release, and thus, inhibit nicotineinduced behaviors, indicating their potential as nicotine addiction treatments. Brain bioavailability, pharmacokinetics and metabolism of the lead candidates will also be evaluated. Comparison of results using native and recombinant nAChRs will provide new insights into the subunit composition of nAChRs mediating these functions. Drug candidates will be assessed for their ability to decrease nicotine self-administration, to decrease nicotine-induced reinstatement of nicotine seeking behavior, and to precipitate withdrawal in nicotine-dependent animals. Thus, an integrative approach (i.e., medicinal chemistry, pharmacokinetics, metabolism, pharmacology, psychology and neuroscience) will be used to increase our understanding of the underlying mechanisms of tobacco use and nicotine addiction, with focus on pharmacotherapeutic candidate development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEVELOPMENT OF LIGANDS FOR NICOTINIC RECEPTORS Principal Investigator & Institution: Carroll, Frank I.; Vice President; Research Triangle Institute Box 12194, 3040 Cornwallis Rd Research Triangle Park, NC 27709 Timing: Fiscal Year 2002; Project Start 05-MAY-1999; Project End 31-JUL-2007 Summary: (provided by applicant): Nicotine abuse leads to approximately 430,000 deaths a year in the United States. Even though most smokers want to quit, only 3% can do so without the use of other intervention. Both the psychological and physiological effects of tobacco smoke (smoking) are attributed to nicotine. The goal of this application is to discover and develop medications for the treatment of smokers. However, we expect that the compounds developed will also serve as biochemical probes useful in gaining a better understanding of the biochemical and molecular mechanisms of nicotine addition and withdrawal. Neuronal nicotinic acetylcholine receptors (nAChRs) are widely distributed throughout the central and peripheral nervous systems including several regions of the brain. Two major classes of nAChRs, alpha4beta2 and alpha7, have been identified in rat and human brains. The possibility exists that specific subtypes mediate specific functions, especially as this relates to nicotine addiction. Thus, the availability of a variety of ligands that bind with high affinity and selectivity for each subtype class is needed. It is also desirable to have both agonists and antagonists since the role of nAChRs in addiction is not known. Epibatidine is a nicotinic agonist whose biological effects appear to be mediated largely by alpha4beta2 nAChRs. Methyllycaconitine (MLA) is the most potent non-peptide
40 Nicotine
competitive antagonists at U-7 neuronal nAChRs thus far reported. The high potency of epibatidine for uAP2 nAChRs and the potency and selectivity of MILA toward the brain alpha7 receptor makes these agents very useful lead compounds for the development of new ligands for studying these nicotinic subtypes. The objective of the research proposed in this application is to conduct SAR studies to develop novel epibatidine and MILA analogs for probing (alpha4beta2 and alpha7 nicotinic receptors. Pharmacological profiles of compounds identified as potent and/or selective for one of the subtypes will be examined for modulation of rodent behavior (antinociception and motor activity), for their ability to substitute for nicotine in rat discrimination, and for their ability to change nicotine self-administration in rats. Selected compounds will be studied at various alpha,beta and alpha7 combinations expressed in Xenopus oocytes to determine the nAChR subtype binding and functional profiles. Since little is known about the in vivo disposition of nAChR both before and after chronic nicotine exposure, PET and SPECT ligands will be developed to identify specific brain regions involved and to help resolve the role various nAChR subtypes play in the addiction process. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEVELOPMENTAL EXPOSURE TO NICOTINE Principal Investigator & Institution: Poland, Russell E.; Professor and Director of Research; Cedars-Sinai Medical Center Box 48750, 8700 Beverly Blvd Los Angeles, CA 90048 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-JUL-2004 Summary: (provided by applicant) This is an R21 application to explore the development of an animal model to study the effects of parental and peripuberal exposure to nicotine. Nicotine remains an important drug of abuse worldwide. In the United States (U.S.), tobacco use is the single leading preventable cause of death. However, despite considerable negative publicity and health warnings, approximately 25 percent of the U.S. population still smoke. Aside from producing profound behavioral effects in the adult organism, nicotine also disrupts developmental processes in many species. Recent epidemiologic data suggest that fetal exposure to nicotine increases the risk for tobacco use during adolescence and adulthood, particularly in females. In addition, 75 percent of adult tobacco users report their first tobacco use occurred when they were "youngsters" (childhood or adolescence). In order to study this issue further, as well as to develop an animal model to elucidate potential underlying mechanisms, the effects of nicotine exposure during gestation on nicotine selfadministration in adult male and female rat offspring will be studied. In addition, the effects of nicotine exposure during the periadolescent period on nicotine selfadministration in adult offspring will be ascertained. It is hypothesized that nicotine exposure in utero will increase nicotine self-administration in adult offspring. Similarly, peripuberal exposure to nicotine also will increase nicotine self-administration during adulthood. The proposed studies will characterize the relationships between exposure to nicotine during critical periods of development and the acquisition, maintenance, extinction and re-initiation phases of nicotine self-administration. The results of these experiments should provide new and important insights on the relationships between prior nicotine exposure and nicotine-seeking behavior. In addition, since nicotine is considered as a "gateway" drug for the subsequent use of alcohol and other illicit drugs, the results of the proposed studies will lay the groundwork to further understand the factors which might increase vulnerability to drug addictions in general, and to nicotine abuse, in particular. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
Studies 41
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Project Title: DISEASE MANAGEMENT FOR SMOKERS IN RURAL PRIMARY CARE Principal Investigator & Institution: Ellerbeck, Edward F.; Associate Professor; Preventive Medicine and Public Health; University of Kansas Medical Center Msn 1039 Kansas City, KS 66160 Timing: Fiscal Year 2003; Project Start 09-JUL-2003; Project End 30-JUN-2008 Summary: (provided by applicant): Cigarette smoking and complications from cigarette smoking disproportionately affect people living in rural communities. Previous strategies to promote smoking cessation have largely been urban-based, involved short term interventions, enrolled smokers already motivated to quit, and been poorly integrated into primary care practice. Nicotine addiction may be better conceptualized as a chronic illness that might be most effectively addressed using newer models of chronic disease management. A disease management approach to smoking cessation would provide support for multiple quit attempts, treat smokers of all stages of readiness to quit, and coordinate cessation efforts with primary health care providers. The primary aim of this study is to assess the effectiveness of both high and low intensity, disease management programs for nicotine dependence. In this study, we will recruit 750 smokers from 20 rural, primary care clinics in Kansas. Subjects will be randomly assigned to one of three study arms, each providing 20 months of treatment: C (comparison group), LDM (low-intensity disease management) or HDM (highintensity disease management). Participant's in-group C will receive health educational mailings and an offer for free nicotine replacement therapy (six weeks) or bupropion (seven weeks) every 6 months (months 0, 6, 12, and 18). Participants in LDM will receive the same interventions as C plus a low-intensity disease management program that includes a single telephone counseling session using motivational interviewing (MI)at months 0, 6, 12, and 18 to encourage a cessation attempt and also includes coordination of smoking assessments and pharmacotherapy with the patient's physician. HDM participants will receive C plus a high intensity disease management program that includes up to six telephone-based MI counseling sessions at months 0, 6, 12, and 18 to encourage a smoking cessation attempt and to prevent relapse after a quit attempt, as well as coordination of smoking assessments, quit attempts, and pharmacotherapy with the patient's physician. The primary outcome of the study is 7-day point prevalence abstinence from cigarettes at 2 years after enrollment. Secondary outcomes include: 1) number of quit attempts and 2) progress in stage of change. If successful, this intervention will provide a generalizable model for addressing nicotine dependence that could improve long-term management of smoking in primary care. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DOPAMINERGIC MECHANISMS IN NICOTINE ADDICTION Principal Investigator & Institution: Brauer, Lisa H.; Assistant Professor; Psychiatry; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, MN 554552070 Timing: Fiscal Year 2001; Project Start 15-SEP-1997; Project End 23-AUG-2002 Summary: There is considerable evidence that nicotine plays a primary role in the maintenance of smoking behavior, but the precise neurochemical mechanisms by which nicotine exerts its rewarding effects remain unclear. Gaining a better understanding of how nicotine functions to reinforce smoking behavior may ultimately lead to the development of new smoking cessation strategies. Nicotine produces a variety of pharmacological effects in the central nervous system, including enhancement of dopamine (DA) levels in mesolimbic brain areas. Studies with laboratory animals as
42 Nicotine
well as preliminary data from human smokers suggest that these effects of nicotine may contribute to its reinforcing effects. The purpose of the proposed studies is to further evaluate the role of DA in cigarette smoking in humans. We will evaluate the effects of two dopaminergic agents, alone and in combination, on acute subjective and behavioral responses to smoking, as well as on rates of ad lib smoking. Measuring both rate of smoking and subjective responses will enable us to determine the behavioral consequences of modulations in smoking satisfaction and to determine whether the acute rewarding effects of smoking and rates are differentially influenced by DA systems. Subjects will smoke both nicotine-containing and de-nicotinized cigarettes. The de-nicotinized cigarettes will serve as a control condition for the sensory aspects of smoking. Using a within-subjects, placebo-controlled design, Study 1 will examine the effects of the DA agonist, bromocriptine, on acute subjective and behavioral responses to smoking and on cigarette consumption in smokers who are overnight abstinent. In Study 2, we will assess the effects of the DA antagonist, haloperiodol, on smoking rates and acute responses. Finally, in Study 3, the effects of combined administration of bromocriptine and haloperidol will be explored. Previous studies have shown that the combined administration of nicotine and the nicotine antagonist, mecamylamine, reduced smoking and attenuated responses to cigarettes to a significantly greater extent than either treatment alone, and resulted in fewer side effects. We will explore the extent to which the effects of combined agonist/antagonist administration extend to the DA system. If this treatment approach does generalize across neurochemical systems, we expect to obtain similar results in this study to those obtained with nicotine and mecamylamine. We hypothesize that combined administration of bromocriptine and haloperiodol will attenuate the subjective and reinforcing effects of smoking to a significantly greater extent than either drug along, and will yield a better side effects profile. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DOSIMETRY OF RISK FOR LUNG AND BLADDER CANCER AMONG CIGA Principal Investigator & Institution: Djordjevic, Mirjana V.; Institute for Cancer Prevention 1 Dana Rd Valhalla, NY 10595 Timing: Fiscal Year 2001 Summary: During the past four decades the cigarette consumption in the U.S.A. gradually changed from high-nicotine, high-"tar" to low-nicotine, low- "tar" brands. Concurrently, there was also a gradual shift observed in the major types of cancer and sites within the lung in cigarette smokers. These changes went from predominance of squamous cell carcinoma, located primarily in the bronchi, to adenocarcinoma in the peripheral lung. It is our working hypothesis that the reduction of the smoke yields of U.S. cigarettes and especially that of the addicting nicotine (sales weighted average changed from 2.7 mg in 1955 to 0.85 mg in 1993) resulted in deeper inhalation of the smoke and thus greater exposure of the peripheral lung to cigarette smoke carcinogens. Increased exposure is also to be considered since more intense smoking of low-nicotine cigarettes leads to higher yields of nicotine and certain carcinogens. Four groups of white and African-American male and female smokers of low- (1.2) nicotine cigarettes will be studied to assess the relationship between their smoking habits and their actual exposure to nicotine, "airborne", and "bloodborne" carcinogens. Currently, the exposure to nicotine and "tar" is assessed on the basis of FTC data. These are established with standard machine-smoking parameters which were developed in 1936. This method does not reflect the smoking habits of today's cigarette smokers. This project together
Studies 43
with the risk estimates established in Project 1 for the major types of lung cancer among smokers of cigarettes with low-, medium-, and high-nicotine content, will result, for the first time, in meaningful estimates of exposure to nicotine and to nicotine-derived carcinogens for each of the three classes of cigarettes. The study will also clarify if the low-nicotine cigarette is indeed less "harmful" than the medium- and high-nicotine cigarette. This study has major public health implications. Lung cancer remains the leading cause of cancer death in the U.S.A, while the overall mortality rate from lung cancer continues to rise. Currently, cigarette smoking contributes to more than 90% of the lung cancer deaths in American men and to more than 75% in American women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EFFECTS OF CHRONIC EXPOSURE TO SMOKING STIMULI Principal Investigator & Institution: Donny, Eric C.; Psychiatry and Behavioral Scis; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2003; Project Start 05-JUN-2003; Project End 31-MAY-2005 Summary: (provided by applicant): Smoking remains a major public health problem, contributing to the death of millions of people worldwide every year. Greater understanding of the mechanisms that drive smoking behavior is needed to prevent additional people from becoming tobacco dependent and improve treatment for current smokers. To date, most research has focused on the primary reinforcing effects of nicotine. However, current evidence suggests that non-nicotine factors, including the sensorimotor stimuli associated with nicotine delivery, are also important. Animal research has shown that nicotine-associated stimuli potentiate acquisition, support maintenance, retard extinction, and facilitate reacquisition of nicotine selfadministration. Similarly, human experimental work has demonstrated that smoking stimuli determine, to a large extent, smoking satisfaction, relief from withdrawal and craving, and smoking reinforcement. However, the effects of smoking stimuli have, almost exclusively, been studied during brief, laboratory sessions. The specific aims of this proposal are to assess the positive subjective, craving-reducing, withdrawal attenuating and reinforcing effects of smoking stimuli in the absence of nicotine, and to determine whether these effects dissipate during an extended period of exposure. The proposed study will compare the effects of smoking denicotinized, smoking nicotine containing cigarettes and not smoking, in a randomized, between-subjects, inpatient design. Participants will reside for twelve nights at the Johns Hopkins Bayview General Clinical Research Center. During this time, combinations of unrestricted smoking, subjective measures of both the positive effects of smoking and withdrawal-relief, sleep recordings, and controlled laboratory assessments of smoking effects, smoking topography and smoking reinforcement will be employed. The results are likely to extend current knowledge of 1) the mechanisms maintaining smoking behavior, 2) nonnicotine, factors promoting smoking during abstinence from nicotine, and 3) changes in the effects of smoking stimuli following repeated exposures. This knowledge will help clarify the treatment needs of smokers trying to achieve abstinence from tobacco. If the reinforcing effects of smoking stimuli prove to be important determinants of smoking behavior, current focus on nicotine alone is inadequate. Novel treatment strategies (e.g., extinction or sensorimotor stimulation replacement therapies), that specifically address the sensorimotor effects of smoking, would be warranted. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
44 Nicotine
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Project Title: EFFECTS OF FAMILY SMOKING HISTORY IN NEVER-SMOKERS Principal Investigator & Institution: Pomerleau, Ovide F.; Professor of Psychology in Psychiatry; Psychiatry; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, MI 481091274 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-MAY-2007 Summary: (provided by applicant): Individual differences in initial sensitivity to nicotine may play a significant role in determining whether or not a person becomes a smoker. In people with high susceptibility, the initial response to nicotine seems to include not only aversive effects but also reinforcing consequences such as pleasurable effects and temporary improvements in affect or performance, and further exposure leads to rapid development of tolerance to aversive effects and sensitization of positive effects, resulting in nicotine dependence. The concentration of people with high susceptibility among those who continue to smoke may explain the difficulty encountered in reducing the prevalence of smoking much below 25 percent over the past decade. To manage this important public health problem more effectively, there is a pressing need to identify the individual behavioral and biological characteristics that set the stage for nicotine reinforcement as well as those factors that interfere with it. The proposed research involves comparisons of sensitivity to nicotine in people who have a positive or a negative family smoking history; never smokers have been chosen for study, rather than current or former smokers, in order to avoid the influence of extensive nicotine exposure on tolerance and sensitization. The approach is comparable to that which has been employed to study the children of alcoholics and other drug abusers. Over a five-year period, the responses of men and women with positive or negative family histories will be investigated, employing both within-subject and between group comparisons. The reinforcement potential of nicotine will be explored by determining reactivity to nicotine administration via nasal spray; subjective, physiological, cognitive, and neuroendocrine response systems will be examined to provide a multi-dimensional assessment. Determination of differences in initial reactivity to nicotine along with identification of baseline characteristics that may contribute to nicotine reinforcement, such as personality variables, psychiatric cofactors, and environmental factors, should increase the understanding of the conditions that promote or protect against smoking behavior, providing the basis for more effective prevention programs and more efficient treatment interventions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EFFECTS OF NICOTINE IN SMOKERS WITH ANXIOUS MOOD Principal Investigator & Institution: Baker-Morissette, Sandra L.; Psychology; Boston University Charles River Campus 881 Commonwealth Avenue Boston, MA 02215 Timing: Fiscal Year 2003; Project Start 25-SEP-2003; Project End 30-JUN-2008 Summary: (provided by applicant): This request for a Mentored Patient-Oriented Research Career Development Award (K23) is made by Dr. Sandra Baker-Morissette to foster her academic and research career development as a clinical scientist in smoking, nicotine dependence and psychiatric comorbidity. Dr. Baker-Morissette's career development plan spans 5 years, during which she will continue to work closely with her sponsor, Dr. Gulliver, as well as her co-mentors, Drs. David Barlow, David Spiegel, and Stephen Tiffany. Statistical consultation will be provided by the Boston University School of Medicine. Her career plan includes individual meetings with each mentor, mentorship team meetings, and coursework in statistical analysis and ethics. Her shortterm goals are to expand upon her theoretical, methodological, and statistical skills
Studies 45
needed to become a highly productive clinical scientist and to develop an independent programmatic line of research. Dr. Baker-Morissette's plan should yield sufficient experience as defined by data collection, grant writing, and paper presentations to advance by the close of the award to Associate Professor. Dr. Baker-Morissette's overarching ambition is to make a meaningful contribution to the knowledge base on tobacco use and comorbid anxiety disorders across the lifespan. Her personal career goal is to progress to Full Professor within the Medical School of Boston University. The proposed study expands on Dr. Baker-Morissette's initial studies of anxiety and tobacco use research by examining the effects of nicotine and mood cue exposure on smoking urge and anxiety in cigarette smokers who have comorbid anxiety disorders. In a between- and within-subjects design, smokers will receive a nicotine (21 mg) or placebo patch in a counterbalanced order across two assessment days. During each assessment day, they will engage in a series of imaginal cue exposures that vary in content: smoking plus anxiety cues, smoking cues alone, anxiety cues alone, and neutral cues. Participants will complete self-report questionnaires prior to and following each exposure, including measures of smoking urge and anxiety. Understanding the effects of nicotine on smoking urge in a psychiatric population is particularly important in light of the difficulty that smokers with psychiatric comorbidity have with quitting smoking. Knowledge of such factors may assist our understanding of conditions that influence the relapse process, as well as the effect of certain cues on smoking urge when individuals are attempting to quit smoking and simultaneously using transdermal nicotine replacement therapy. In sum, this research will foster the career development of Dr. Baker- Morissette, and ensure the next step of her programmatic research, which has an excellent probabilit3-to increase our understanding of the links between nicotine, negative affect and tobacco use disorder. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EFFECTS OF NICOTINE ON EMOTIONAL REACTIVITY Principal Investigator & Institution: Carter, Brian L.; Behavioral Science; University of Texas Md Anderson Can Ctr Cancer Center Houston, TX 77030 Timing: Fiscal Year 2001; Project Start 10-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant): Dr. Brian Carter, a graduate from Purdue University in clinical psychology, is a fellow in the R25 Cancer Prevention Training Program at M.D. Anderson Cancer Center. Dr. Carter has an extensive background in addiction research with a specific interest in smoking behavior. Dr. Carter's immediate goal is to use the support of the K07 to establish an independent program of research and, over the course of the award, develop a career in preventive oncology, specializing in the development of more efficacious smoking cessation treatments. The career plan includes a series of formal coursework and seminars (e.g., Human Genetics, NCI Summer Curriculum in Cancer Prevention), and the mentoring support of M.D. Anderson faculty members Drs. Paul Cinciripini (smoking cessation, physiological aspects of smoking), David Wetter (smoking cessation), Ellen Gritz (cancer prevention, tobacco control), Robert Chamberlain (cancer epidemiology), and Carl de Moor (biostatistics). M.D. Anderson, one of the leading comprehensive cancer centers in the world, has a focus on research and training with numerous didactic and collaborative opportunities. The following research is proposed. The DRD2 A1 allele has been associated with a higher prevalence of smoking, as well as smoking cessation relapse, and is believed to be associated with impaired dopaminergic function leading to an increase in negative mood. The dependence producing properties of nicotine have been related to its ability to stimulate dopamine release, which may be partly responsible for the strong
46 Nicotine
relationship between smoking and mood. The startle reflex (eye blink) that follows an unexpected auditory stimulus varies in magnitude with the valence of simultaneously presented emotional cues: negative emotional cues increase blink magnitude, while positive cues reduce or inhibit the response. As such, the startle reflex is regarded as a near instantaneous measure of emotional processing. Smokers will be genotyped as carrying the DRD2 Al or A2 allele, and their mood changes (via eye blink response) as the result of acute administration of nicotine, will be assessed. These same smokers will carry, in their natural environment, a hand held computer into which they will record mood data before and after smoking a cigarette. This study will compare the mood altering profiles of nicotine, from the same sample of smokers, from both laboratory and naturalistic settings. This data will offer a more comprehensive account of the relationship between smoking and mood, and provide insight into how some smokers (based on genetic make up) may be using nicotine to regulate mood. This could provide an important assessment tool that will lead to more effective treatment plans that focus on individually targeted mood management techniques. Future studies will add to this research design a nicotine/placebo patch treatment component. Structural equation modeling will be used to design an abstinence model based on smoker variables (e.g., genetics). This model will identify which smokers benefit most (or least) from nicotine replacement. In addition, a similar research design will employ cigarette-related stimuli which will offer a more comprehensive examination of the relationships among genetics, mood, and craving for cigarettes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ENABLING TECHNOLOGIES IN FMRI AND CIGARETTE SMOKING Principal Investigator & Institution: Cohen, Mark S.; Professor; None; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, CA 90024 Timing: Fiscal Year 2001; Project Start 25-JUN-2001; Project End 31-MAY-2003 Summary: (Adapted from applicant's abstract) While functional neuroimaging has made great inroads in neuroscience, the applications of functional Magnetic Resonance Imaging (fMRI) to the study of cigarette addiction have been limited. The applicants believe that this is the consequence, in large part, of technical issues that include the difficulty of creating a normal smoking environment (or even of administering cigarette smoke), and the unknown direct effects of the many components of cigarette smoke on the overall sensitivity of the imaging experiments (most of which depend on vascular effects for their signal). In the preliminary studies, The applicants have developed an approach to cigarette smoke delivery that is fully compatible with fMRI and can deliver much of the normal smoking experience during an imaging session. The applicants have shown that this device can mimic important features of normal smoking, including changes in CO, behavioral satisfaction and nicotine blood level. The applicants also demonstrate that we can examine brain signal changes during smoking and have a means to compare fMRI activation signals before and after smoking. In the research plan that follows, the applicants propose to characterize fully the psychological and physiological effects achieved with our in-magnet smoking device and to study carefully the fMRI activations before, during and after smoking. Further, in order to distinguish between effects of nicotine and smoking per se and to facilitate future experiments, the applicants will study these changes after smoking of normal (NIC+) and reduced nicotine (NIC-) cigarettes. With these data in hand, the applicants should be well positioned to use fMRI to probe many outstanding questions in the neurobiology of compulsive smoking. For example, what specific brain regions are involved in craving and its satisfaction by cigarette use? What is the neural basis for the
Studies 47
changes in cognitive task performance that characterize withdrawal? What brain areas mediate the separable component effects of nicotine and other aspects of cigarette smoking? What physiological factors underlie shifts in brain lateralization associated with smoking and abstinence? The methods developed in this grant will give scientists new tools for exploring these questions; the answers they find may help to develop new treatments for nicotine addiction and to understand why some individuals are more vulnerable to this life-threatening disorder. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ENVIRONMENTAL ENRICHMENT AND THE RESPONSE TO NICOTINE Principal Investigator & Institution: Green, Thomas A.; Psychology; University of Kentucky 109 Kinkead Hall Lexington, KY 40506 Timing: Fiscal Year 2001; Project Start 01-OCT-2001; Project End 30-JUN-2002 Summary: There is considerable research on the effects of different rearing environments on the subsequent response to amphetamine. The most consistent finding in the literature is that rats raised in an enriched environment show enhanced sensitivity to the behavioral and neurochemical effects of amphetamine compared to rats raised in an impoverished environment. One mechanism proposed to explain this effect is via enhanced reversal of the dopamine transporter. In contrast to amphetamine, nicotine facilitates clearance of dopamine in terminal regions of the ascending dopaminergic pathways. Correspondingly, preliminary evidence in the present proposal shows that environmental enrichment confers a decrease in sensitivity to the locomotor stimulant effect of nicotine. Based on this differential sensitivity to the stimulant effect of nicotine, the experiments proposed in this application seek to assess the effects of differential rearing on the reinforcing efficacy of nicotine using an intravenous self-administration paradigm with rats. In addition, these experiments are also designed to elucidate the underlying mechanism(s) mediating the differential behavioral response to nicotine using in vivo chronoamperometric voltammetry to measure clearance of exogenously applied dopamine. Results from these experiments will provide preclinical evidence about the role of environmental enrichment during development in the etiology of tobacco dependence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EPIDEMIOLOGICAL/FAMILIAL ASPECTS OF DRUG USE Principal Investigator & Institution: Kandel, Denise B.; Professor of Public Health in Psychiatry; Psychiatry; Columbia University Health Sciences New York, NY 10032 Timing: Fiscal Year 2001; Project Start 05-AUG-1981; Project End 31-JUL-2006 Summary: (Provided by Applicant) This is a competing continuation application for renewal (Years #21-#25, 8/l/01-7/31/06) of a K05 Senior Scientist Award (SSA) held since 8/01/81. The overall objective of the research has been to investigate through epidemiological studies three major themes on substance use in adolescence and adulthood: developmental patterns of involvement and cessation in the use of various drugs; risk and protective factors for involvement in drugs; and consequences of using drugs. Stimulated by findings obtained in the current period of support, the goal for the next five years is to conduct a multifactorial examination of the development of nicotine dependence. Six specific aims will be pursued: (1) Describe the epidemiology and natural history of nicotine dependence and other aspects of smoking behavior, in particular the transition to daily smoking and nicotine dependence, among adolescents
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and young adults. (2) Identify psychological, social and biological factors that promote (risk factors) and factors that reduce the risk (protective factors) of daily smoking and the transition to nicotine dependence. (3) Specify the comorbidity of drug use and dependence with psychiatric symptoms among adolescents, in particular the sequencing and reciprocal relationships between nicotine dependence and depression. (4) Examine interpersonal influences on drug behavior, especially nicotine dependence, within and outside the family, and identify: a. the extent of familial similarity on drug behavior, including nicotine dependence, among parents and adolescents, siblings, and spouses; b. the relative contribution of genetic, shared and non-shared environmental factors to smoking onset, daily smoking and nicotine dependence among twins; c. the relative importance of selection and socialization on smoking among adolescent friendship pairs. (5) Identify pathways of progression in smoking, nicotine dependence, and the use of other drugs. (6) Identify gender and ethnic commonalities and differences for #1#5. An overall goal is to incorporate a biological perspective in epidemiological research. Three interrelated research programs will be pursued to achieve these aims: analyses of a national longitudinal sample of young adults (Add Health), analyses of the National Household Surveys on Drug Abuse, and the implementation of a new longitudinal study of the transition to nicotine dependence in adolescence. The research will provide understanding crucial for the development of effective prevention and treatment interventions. Components of the program represent innovative activities in epidemiological research carried out on general population samples. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RECEPTORS
ETHANOL
EFFECTS
ON
NICOTINIC
ACETYLCHOLINE
Principal Investigator & Institution: Nowak, Mark W.; Professor; Psychiatry and Behavioral Scis; Medical University of South Carolina 171 Ashley Ave Charleston, SC 29425 Timing: Fiscal Year 2001; Project Start 01-AUG-1999; Project End 31-JUL-2004 Summary: This proposal is a K01 Mentored Scientist Development Award Application. The candidate, Dr. Mark W. Nowak, is an Assistant Professor in the Center for Drug and Alcohol Programs (CDAP) at the Medical University of South Carolina. A K01 award would allow the candidate to integrate his existing research skills in the study of nicotinic acetylcholine receptors (nAChRs) with the field of alcohol research. While the candidate has research experience in the study of nAChRs, he has no prior research experience in the alcohol field. The proposed training plan is designed to provide the candidate with a broad knowledge of alcohol-related research through didactic work, training in electrophysiological and tissue culture techniques specific to ethanol research, and "hands-on" training in the use of animal models involving in vivo ethanol exposure. Within CDAP, there are established researchers in the alcohol field, thus ensuring the successful completion of the training objectives. Further, the proposed research project described below complements these training objectives and addresses the candidate's research interests in developing an independent research program focused on nicotine-ethanol interactions. Understanding ethanol-nicotine interactions is a relevant health issue given the well-documented comorbid use of alcohol and tobacco products. While the reasons for the combined use of these substances are not wellunderstood, there is a growing body of evidence suggesting involvement of ethanolnicotine interactions in the CNS. Ethanol and nicotine have been shown to affect a wide variety of neurochemical systems in the brain. The main CNS target for nicotine are the neuronal nAChRs. It is reasonable to suggest that neuronal nAChRs may, in part, be
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involved in central ethanol/nicotine interactions. Nevertheless, while the effects of ethanol on other ligand-gated ion channels (NMDA, GABAA and 5-HT3 receptors) have received considerable attention, the effects of ethanol on neuronal nAChR function have not been extensively studied. To address this research question, the proposed research studies will examine the effects of acute and chronic ethanol exposure on neuronal nAChR function. Electrophysiological whole-cell patch clamp techniques will be utilized to assess neuronal nAChR function in primary rat hippocampal neuronal cultures. The findings from the proposed studies will contribute to the long-term goal of understanding the effects of ethanol and nicotine on brain function. Overall, this K01 award would allow Dr. Nowak to expand his experimental skills into the field of alcohol research as well as achieve his goal of developing an independent research program studying alcohol-nicotine interactions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EXAMINATION COADMINISTRATION
OF
ALCOHOL
AND
NICOTINE
Principal Investigator & Institution: Sharpe, Amanda L.; Physiology and Pharmacology; Wake Forest University Health Sciences Winston-Salem, NC 27157 Timing: Fiscal Year 2001; Project Start 01-MAR-2001 Summary: The co-use of alcohol and nicotine is positively correlated in man, with people who drink alcohol having an increased probability of smoking and vice versa. Although alcohol and nicotine are known to be one of the most common combinations of drugs abused by man, little is known about the relationship between these two drugs. The experiments proposed will examine the interaction between these drugs in rats by investigating the effect of self-administration of one drug on the subsequent selfadministration of the other drug as well as the concurrent administration of both. The hypothesis being tested predicts that alcohol and nicotine are interacting by a pharmacological mechanism and that self-administration of one drug will be affected only when the other drug is present. These experiments are unique because the rats will be able to self-administer both nicotine (intravenously) and alcohol (orally) during daily operant sessions. Examination of the relationship between alcohol and nicotine using this procedure will develop a model that can be used for further determination of the mechanism of the interaction between these two drugs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EXERCISE AND NICOTINE REPLACEMENT FOR FEMALE SMOKERS Principal Investigator & Institution: Kinnunen, Taru; Oral Health Policy & Epidem; Harvard University (Medical School) Medical School Campus Boston, MA 02115 Timing: Fiscal Year 2001; Project Start 15-APR-1999; Project End 31-MAR-2002 Summary: Each year nicotine addiction is responsible for more than 125,000 deaths of American women. In 1987, cigarette smoking related lung cancer surpassed breast cancer as the leading cause of death by cancer among women. The prevalence of smoking has declined more slowly for women than for men, suggesting that quitting smoking is more difficult for women. Factors that may contribute to the gender difference in cessation rates include women's greater tendency to smoke as a means of coping with negative affect, and their greater concern about postcessation weight gain. It seems clear that special interventions are needed to address these unique concerns of female smokers. Nicotine replacement therapy has shown some success in improving
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smoking cessation rates, reducing the severity of negative affect usually experienced during cessation, and, in the case of nicotine gum, minimizing postcessation weight gain. Aerobic exercise has also been found to improve mood and control weight. In combination, nicotine replacement therapy and aerobic exercise should be a powerful smoking cessation treatment for women. The proposed study will investigate the effects of an aerobic exercise intervention as an adjunct to nicotine polacrilex gum therapy. Three hundred female smokers will receive nicotine gum therapy and will be randomly assigned to an exercise intervention, an equal contact control condition, or a gum alone control condition. The exercise intervention will consist of three 45-minute sessions of aerobic exercise per week from 3 weeks precessation through 16 weeks postcessation. All participants will be followed for one year after cessation. In addition to determining the effectiveness of the adjunct exercise intervention on cessation rates, the mechanisms (e.g., relief of negative moods, suppression of cessation-related weight concerns, relief of premenstrual distress) by which exercise affects cessation will be examined. The proposed study will provide the first large-scale test of a very promising intervention to aid women in smoking cessation. The combination of an exercise intervention with nicotine replacement, which has not yet been investigated, should provide a particularly effective treatment program for female smokers. Intensive focus on the mechanisms by which exercise affects cessation will provide information essential both for understanding the nature of the relationship between exercise and smoking cessation, and for later refinement and enhancement of the exercise intervention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FETAL & ADOLESCENT NICOTINE EFFECTS ON CNS 5HT SYSTEMS Principal Investigator & Institution: Slotkin, Theodore A.; Professor; Pharmacology and Cancer Biology; Duke University Durham, NC 27706 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-MAY-2004 Summary: We have developed rodent models of prenatal nicotine exposure that simulate the plasma levels found in smokers or in users of the transdermal nicotine patch, and have demonstrated that nicotine itself is a neuroteratogen that elicits synaptic functional changes appearing after an extended period of apparent normality. These effects target catecholamine systems and we have preliminary data indicating involvement of 5HT systems as well. Brain development continues into adolescence, the period in which nearly all smokers begin smoking, and we have developed a comparable rodent model of adolescent nicotine administration; again, catecholamine systems are targeted and we have preliminary data for 5HT. It is clear that a subset of smokers are using tobacco to self-medicate for depression; additionally, adolescent smoking is associated with higher incidence of subsequent depression. These findings lead to the current hypothesis: namely that nicotine, during a critical period of brain development, alters the set-point for 5HT activity, at the level of presynaptic function, at receptor signal transduction cascades, or both. This will be pursued in fetal and adolescent nicotine exposure models, utilizing neurochemical, cell signaling, and behavioral approaches. Aim 1. To determine how prenatal nicotine exposure alters 5HT synaptic function and behaviors known to be targeted in models of 5HT dysfunction. Evaluate development of 5HT projections, using nerve terminal markers, 5HT turnover, and the ability of acute nicotine challenge to release 5HT; studies conducted from birth to adulthood. 5HT signal transduction assessed with receptor ligand binding and linkages to adenylyl cyclase. Aim 2. To determine whether the critical period for nicotine- induced alterations in the programming of 5HT function extends into
Studies 51
adolescence. We will assess 5HT synaptic function and behaviors during adolescent nicotine treatment and withdrawal, using the same endpoints as studied with the prenatal nicotine model. Aim 3. To determine whether prenatal nicotine exposure alters the response to subsequent adolescent nicotine administration. Animals exposed prenatally to nicotine will receive adolescent nicotine treatment and the response of 5HT systems and behavior will be assessed, along with catecholaminergic responses and nicotinic receptors known to be affected by adolescent nicotine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FETAL NEURODEVELOPMENT--EFFECTS OF NICOTINE AND HYPOXIA Principal Investigator & Institution: Stark, Raymond I.; Professor; Columbia University Health Sciences New York, NY 10032 Timing: Fiscal Year 2001 Summary: Prenatal exposure to nicotine through maternal smoking leads to alterations in fetal responses related to arousal and cardiorespiratory control far beyond the period of exposure. The drug pets fetuses at increased risk for growth restriction, prematurity, perinatal complications and after birth, for the Sudden Infant Death Syndrome, behavioral and learning disabilities, and attention deficit disorders; while the adolescent female offspring may be at increased risk for becoming smokers themselves. By hypoxia and direct effects of nicotine on fetal neurodevelopment have been implicated as mechanisms for this array of consequences. Our overall hypothesis is that excessive and untimely stimulation of fetal nicotinic receptors by nicotine induces wide ranging structural and functional changes in the developing nervous system leading to alterations in central regulatory mechanisms controlling autonomic and behavioral functions. While fetal regulatory mechanisms adapt to chronic nicotine exposure to maintain a relatively "normal" physiology, hypoxic stress will reveal deficiencies in physiologic competence. These structural functional alterations, established in utero produce a "vulnerable" newborn who will have a life long risk for stress related pathologies. To test these hypotheses, we will compare key markers of neurophysiologic function (coordinated fetal states, response to hypoxia and baroreceptor gain) in nicotine exposed fetuses with controls and relate their functional impairments to structural differences in brainstem and forebrain arousal and cardiorespiratory centers. Studies are carried out in a unique chronically instrumented baboon model. The homologies in neurodevelopment between the human and baboon fetus make knowledge gained from this research relevant to identifying high risk fetuses and infants. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: FETAL NICOTINE EXPOSURE EFFECT ON PRIMATE LUNG Principal Investigator & Institution: Spindel, Eliot R.; Senior Scientist; None; Oregon Health & Science University Portland, OR 972393098 Timing: Fiscal Year 2001; Project Start 01-FEB-1999; Project End 31-JAN-2004 Summary: The deleterious effects of maternal smoking during pregnancy are all too well established. Maternal smoking is the major preventable cause of intrauterine growth retardation and prematurity. Perhaps less well appreciated, is the recent, overwhelming evidence, that smoking during pregnancy directly and adversely effects lung development. Respiratory problems associated with in utero tobacco exposure include decreased lung function, increased respiratory diseases and increased incidence of
52 Nicotine
sudden infant death syndrome (SIDS). Given the unfortunate prevalence of smoking during pregnancy and the resulting serious consequences, it is of major importance to understand the mechanisms underlying smoking-induced changes in the newborn. Our preliminary data suggests that nicotine itself is one of the factors responsible for the changes in pulmonary function observed in neonates born to smoking mothers. In this application we propose to use the rhesus monkey to characterize the effects of chronic exposure to low levels of nicotine throughout pregnancy on lung development and subsequent pulmonary function. Whole animal studies will be complemented with in vitro studies to begin to determine the molecular mechanisms underlying nicotine's effect on lung. In preliminary studies we have demonstrated that exposure of pregnant rhesus monkeys to a nicotine dose consistent with that of smokers alters fetal airway development and that related effects can be produced in fetal monkey lung organ cultured. Immunohistochemistry shows wide expression of nicotinic receptors in developing lung and nicotine appears to alter the pattern of receptor expression. Preliminary data further suggests that some of the effects of nicotine, acting through nicotinic receptors, may be mediated by antagonism of the mitogenic effects of peptide growth factors. Thus we specifically propose to 1, Determine the basis for nicotine's actions by determining the time course and cell specific expression of nicotinic receptor subtype expression in fetal monkey lung; 2, Characterize the effect of fetal exposure to nicotine on lung development and function by functional, morphometric, immunohistochemical and molecular analysis; and 3, begin to determine the mechanism underlying nicotine's actions by use of fetal monkey lung organ culture. From these studies will come the first description of the effects of chronic nicotine exposure on lung function; a determination of the extent to which these effects are reversible; and a beginning understanding of the mechanisms underlying these effects. Definitive knowledge of the effects of nicotine on lung development would provide an important additional tool in smoking control and will begin to better explain the link between maternal smoking and altered neonatal respiratory function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FUNCT. CHARACTERIZATION OF HUMAN CYP2A6 GENETIC VARIANTS Principal Investigator & Institution: Hong, Jun-Yan; Associate Professor; Environmental & Community Med; Univ of Med/Dent Nj-R W Johnson Med Sch Robert Wood Johnson Medical Sch Piscataway, NJ 08854 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 29-SEP-2003 Summary: (Adapted from the Investigator's Abstract) Cigarette smoking is a major risk factor of human cancers. Human cytochrome P4502A6 (CYP2A6) plays a predominant role in the metabolic activation of N'-nitrosonornicotine (NNN) and 4(methylnitrosamino)-1-(3-pyridyl)-1- butanone (NNK), two major carcinogenic tobaccospecific nitrosamines, as well as in the metabolism of nicotine which is responsible for smoking addiction. Existence of functional genetic polymorphism of CYP2A6 is strongly suggested by the reports on large inter-individual variations (up to 170-fold) in CYP2A6 activity (assayed as coumarin 7-hydroxylase) in general populations, and on bimodal activity distribution. There area a total of 6 genetic variants on human CYP2A6, including 3 missense variants we recently identified. One of the reported missence variants (2A6v1, leu160His) lacked coumarin 7-hydroxylase activity. However, the activities of 2A6v1 and other variants in metabolizing NNN, NNK, and nicotine as well as their importance in tobacco-related carcinogenesis have not been investigated. Our working hypothesis is that functional genetic polymorphisms of CYP2A6, such as
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2A6v1, significantly affects an individual's ability to metabolize NNN, NNK, and nicotine. Therefore, it could be an important determinant in human susceptibility to tobacco-related carcinogenesis. As an essential step to our working hypothesis, the present proposal focuses on the functional characterization of CYP2A6 genetic variants with the following specific aims: 1. To characterize the functional significance of CYP2A6 missense genetic variants through: (a) generation of the variant proteins by site-directed mutagenesis and heterologous expression; (b) comparison of the enzyme kinetics of the variants with the wild-type protein in metabolizing NNN, NNK and nicotine; (c) comparison of NNN- or NNK-induced cytotoxicity in cells transfected with either wild-type or variant CYP2A6 cDNAs; and (d) determination of protein stability of the missense variants. 2. To determine the allelic frequency distribution of functional CYP2A6 polymorphisms in different ethnic populations. This study will provide background information for future epidemiological studies, and provide the genotyped subjects for the human study proposed in specific aim 3. 3. To determine the impact of functional YCP2A6 genetic polymorphisms on the in vivo metabolism of nicotine and coumarin, both probe drugs of CYP2A6, by correlating the urinary metabolic ratio (MR) of nicotine and coumarin with the CYP2A6 polymorphic genotypes in volunteer subjects. Individuals with significant MR alterations not without known CYP2A6 polymorphisms will be used to identify new CYP2A6 variants. Our proposed studies are critical to elucidate the functional importance of CYP2A6 genetic polymorphism and help asses the possibility of using CYP2A6 genetic polymorphism as a susceptibility marker of tobacco-related human carcinogenesis, which could contribute significantly to cancer prevention by identifying susceptible subpopulations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RECEPTORS
FUNCTIONAL
ACTIVITY
OF
MESOLIMBIC
NICOTINIC
Principal Investigator & Institution: Rowell, Peter P.; Pharmacology and Toxicology; University of Louisville University of Louisville Louisville, KY 40292 Timing: Fiscal Year 2001; Project Start 29-SEP-1992; Project End 31-JUL-2003 Summary: Cigarette smoking is a major public health problem in the United States, and nicotine is the principal pharmacological component of tobacco which reinforces smoking behavior. There is compelling evidence that nicotine produces its reinforcing effects by acting on nicotinic cholinergic receptors located on mesolimbic neurons in the brain which release dopamine from terminals of the nucleus accumbens. Studies of nicotinic receptors in other brain areas or in peripheral nerves have shown that, while brief exposure to nicotine produces receptor activation, prolonged exposure to even very low concentrations of nicotine (below the threshold for stimulation) results in receptor desensitization, whereupon subsequent exposure to nicotine does not produce the characteristic functional response. When one considers the blood and brain concentration of nicotine which are present in cigarette smokers throughout the day, it would seem that their receptors should be in a continual state of desensitization. How, then, could nicotine produce any significant reinforcing activity if the receptors upon which it acts have been rendered non-functional? There are a number of possible explanations which will be investigated in the present project. (1) It is possible that the receptors on the mesolimbic neurons do not display the desensitization characteristics determined in previous studies in other tissues and preparations. (2) It is also likely that, even during prolonged desensitization, the nicotine receptors on mesolimbic neurons exhibit sufficient basal or persistent activity to remain functionally responsive to nicotine. (3) There is evidence that glutamate neurons at the somatodendrites or the
54 Nicotine
terminals of mesolimbic neurons can contribute to and perhaps enhance nicotinestimulated dopamine release. (4) It is possible that the increased number of nicotinic receptors which result from chronic drug administration produces an increased response or that these receptors display different desensitization characteristics. These possibilities will be investigated by measuring the functional activity of mesolimbic receptors in intact slices of the ventral tegmental area and nucleus accumbens from nicotine-treated and nontreated rats. The nicotine-stimulated efflux of rubidium following various nicotine treatment schedules, coupled with assays of nicotine brain levels and receptors, will provide valuable new information about how mesolimbic neurons respond to nicotine. These studies are important as we attempt to understand the mechanisms responsible for cigarette smoking and nicotine dependence, as new nicotine replacement therapies become available for smoking cessation, and as nicotine and nicotine analogs find a place in therapeutics for such diseases as Alzheimer's, Parkinson's, ulcerative cholitis, schizophrenia and others. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FUNCTIONS OF NICOTINE RECEPTORS IN SENSORY NEOCORTEX Principal Investigator & Institution: Metherate, Raju S.; Neurobiology and Behavior; University of California Irvine Campus Dr Irvine, CA 92697 Timing: Fiscal Year 2001; Project Start 01-JUL-2000; Project End 30-JUN-2005 Summary: (Adapted from the Investigator's Abstract) A tragic consequence of passive, or "secondhand," exposure to nicotine is the potential impairment of brain development in infants. Neonatal exposure to nicotine can result in children with diminished auditory function and auditory-related language and cognitive deficits. The long term goal of this research is to understand how exposure to nicotine during development impairs auditory cortex function. Recent studies have shown that rapid activation of alpha-7 nicotinic acetylcholine receptors (alpha-7 nAChRs) in developing auditory cortex selectively enhances synaptic potentials mediated by N?methyl-D-aspartate glutamate receptors (NMDARs). This interaction is vulnerable to the effects of exogenous nicotine, and preliminary data indicate that exposure to nicotine at levels found in the bloodstream of smokers selectively affects NMDAR synaptic activity in the developing cortex. The proposed experiments will test the hypothesis that during development, alpha-7 nAChRs regulate glutamate release at pure-NMDAR synapses (synapses that have only NMDARs postsynaptically). These pure-NMDAR synapses convey sensory inputs to auditory cortex. The experiments use a newly-developed brain slice preparation that maintains a functional pathway conveying thalamic information to auditory cortex. Intracellular (whole-cell patch) recordings in the auditory thalamocortical slice and in the intact animal during acoustic stimulation will be used to determine if: (1) alpha-7 nAChRs regulate thalamocortical synapses during development, (2) presynaptic alpha-7 nAChRs regulate pure-NMDAR synapses, (3) chronic exposure to nicotine during development alters glutamate release at pureNMDAR synapses, and (4) chronic exposure to nicotine during development impairs sensory function in the adult. Achieving these aims will contribute to an understanding of developmental mechanisms in sensory cortex, and how development can be disrupted by exposure to nicotine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENDER & NICOTINE WITHDRAWAL--A PLACEBO CONTROL STUDY Principal Investigator & Institution: Buchhalter, August R.; Psychology; Virginia Commonwealth University Richmond, VA 232980568 Timing: Fiscal Year 2001; Project Start 15-JUN-2001 Summary: Understanding factors that influence drug withdrawal in men and women is an essential component of successful drug abuse treatment. This within-subjects study will explore the time course of tobacco withdrawal in men and women over a 5-day period using a placebo control design. Smokers will participate in three, 5-day conditions separated by a minimum 48-hour washout period. Conditions will span Monday-Friday and subjects will attend the research facility for about one hour on each weekday for periodic monitoring on various measures (e.g., subjective, physiological, behavioral, compliance). Weekends will serve as washout periods during which subjects will smoke their usual brand of cigarettes. Conditions vary by the cigarettes to be smoked: in one condition subjects will smoke denicotinized cigarettes, in another they will smoke control (nicotinized) cigarettes, and in the third they will abstain from smoking. Smoking conditions will be double-blind and all these conditions will be ordered by Latin Square. Each condition will include periodic monitoring of subjective symptoms of tobacco withdrawal, performance measures, levels of urinary cotinine (a nicotine metabolite), expired air carbon monoxide (CO), and several physiological variables. Subjective and performance measures will be administered daily, MondayFriday. Monitoring levels of urinary cotinine and expired CO will be done thrice weekly (i.e., Monday, Wednesday, and Friday) and will be used to assess compliance with smoking restrictions. Additionally, compliance with smoking restrictions will be reinforced monetarily twice weekly (i.e., Wednesday and Friday). Results from this study will help to determine: a) the extent to which cigarette smokers are physically dependent on nicotine, the long-term contribution of non-nicotine, tobacco-related factors in the withdrawal suppression produced by denicotinized cigarettes, and c) whether men and women differ in their response to the nicotine/tobacco withdrawal syndrome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENETIC ANALYSIS OF NICOTINE ADAPTATION IN C ELEGANS Principal Investigator & Institution: Schafer, William R.; Associate Professor; Biology; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, CA 92093 Timing: Fiscal Year 2001; Project Start 01-FEB-2000; Project End 31-DEC-2004 Summary: Tobacco use has been implicated in a wide range of human diseases, including heart disease, emphysema, and cancer, which together result in millions of premature deaths each year. The addictive properties of nicotine are a major cause of persistent and compulsive tobacco use. Nicotine addiction is thought to result from long-term adaptive changes in the activity and expression of nicotinic acetylcholine receptors in the brain. However, the molecular and neuronal mechanisms that underlie these adaptive processes remain poorly understood. The goal of this research is to use genetic analysis in a simple animal model, the nematode Caenorhabditis elegans, to investigate the molecular basis of nicotine adaptation. C. elegans is highly amenable to molecular analysis of nervous system function: it has a simple and well characterized nervous system, and its short generation time, small and largely sequenced genome, and accessibility to germline transformation make it ideal for classical and molecular genetic studies. C. elegans exhibits a striking and easily measurable response to nicotine, and
56 Nicotine
long- term nicotine exposure leads to nicotine tolerance and dependence with respect to behaviors controlled by both neuromuscular and neuronal nicotinic receptors. In this project, genes required for nicotine adaptation in nematodes will be identified by screening for adaptation-defective mutants. Two nicotine adaptation genes identified in earlier screens will be cloned to determine their molecular functions, and to characterize the cellular pathways in which they function. The possibility, suggested by studies of protein kinase C-defective mutants, that PKC phosphorylation of nicotinic receptor subunits is a mechanism for nicotine adaptation will be tested through the analysis of transgenic worms expressing mutant receptors. The ultimate goal of this work is to provide a model for the general molecular mechanisms underlying nicotine adaptation in neurons, and to identify new proteins that participate in nicotine addiction in other animals, including vertebrates. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC EPIDEMIOLOGY OF NICOTINE DEPENDENCE Principal Investigator & Institution: Breslau, Naomi%; Washington University Lindell and Skinker Blvd St. Louis, MO 63130 Timing: Fiscal Year 2001; Project Start 28-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant): The proposed epidemiologic family study will systematically examine the vulnerability to nicotine dependence due to the combined transmission of genes and family/cultural environmental factors (i.e., familial liability). Four areas are addressed in the proposed study: 1.) the familial liability for nicotine dependence associated with different phenotypes or characteristics of nicotine dependence (e.g. also meeting DSM-IV criteria); 2.) the degree of shared familial liability between nicotine dependence and other substance use and mental disorders; 3.) the interaction between familial liability for nicotine dependence and non-familial environmental factors in the etiology of nicotine dependence; 4.) familial liability, nonfamilial factors, and individual factors that may be partially under genetic control (such as nicotine metabolism) that contribute to estimated differences in nicotine dependence between African Americans and Caucasians, both to spotlight factors that contribute to nicotine dependence in a group at high risk of cancer mortality (African Americans) and to identify protective factors by comparing racial groups with substantially different cigarette smoking profiles. This epidemiologic case - control family study is designed to examine the familial transmission of nicotine dependence among adults 25 to 44 years of age and their families. This age range will be used because the period of risk for daily smoking is largely concluded by age 25 and adults between these ages are still likely to have living parents. Cases will be nicotine dependent by a threshold score of 4 or more on the Fagerstrom Test of Nicotine Dependence (FTND). Controls will be smoking exposed (having smoked at least 100 cigarettes) but never nicotine dependent (FTND = 0). For cases one sibling and both parents will be sought. For controls one sibling will be sought. Direct interviews will be conducted with the case and control family members. The information gathered will include their cigarette smoking, psychiatric disorders, and other substance use, as well as demographic and medical history information. All of the interviewed family members will provide family history of cigarette smoking, substance use and psychiatric disorders. Additionally, cases and controls will be asked about the cigarette smoking, alcohol use and behavior problems of their offspring. This study provides a population-based context for genetic and metabolism studies in the Collaborative Study on the Genetics of Nicotine Dependence. Ascertainment, interviewing, and data management will be integrated across studies. Additionally, as part of the unique opportunity presented by the scientific integration of Projects 1, 2,
Studies 57
and 3, we will incorporate genetic, metabolic and epidemiologic measures of a broad array for factors in the development of risk factor models for nicotine dependence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC STUDIES OF NICOTINE TOLERANCE-WITHDRAWAL Principal Investigator & Institution: Mccallum, Sarah E.; Inst of Behavioral Genetics; University of Colorado at Boulder Boulder, CO 80309 Timing: Fiscal Year 2001; Project Start 01-MAY-2001 Summary: (provided by applicant) Smoking remains the leading, preventable cause of death in the U.S., yet surprisingly little is known about the causes of nicotine addiction. Chronic nicotine exposure results in behavioral and physiological changes that most likely arise from nicotine binding to neuronal nicotinic receptors (rxAChRs). These changes include chronic tolerance to the effects of nicotine in humans and laboratory animals, and changes in nAChR number and function. There appears to be a genetic component to nicotine tolerance in mice, and similarly, smoking appears to be influenced by genetics. One goal of the proposed set of experiments is to learn to what extent nAChR function is genetically influenced, using inbred mouse strains that differ with respect to the extent of tolerance development. Furthermore, little is known about genetic components of withdrawal from nicotine, and there exist vast differences in withdrawal symptoms in smokers. A mouse model of nicotine withdrawal will be developed in order to examine somatic and motivational components of withdrawal, and investigate any genetic contribution. Also largely unknown are the nAChR subtypes that regulate tolerance and withdrawal. A third goal is to examine the role of beta2 and alpha7 nAChR subunits using beta2 and alpha7 null mutant mice. A major beta2-containing nAChR subtype is the alpha4beta2 nAChR and as it, along with the alpha7 are the most abundant in brain, they will be examined. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENETICS AND CONSEQUENCES OF NICOTINE ADDICTION Principal Investigator & Institution: Hoidal, John R.; Chief, Pulmonary Division; Internal Medicine; University of Utah 200 S University St Salt Lake City, UT 84112 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): This is a revised application from faculty members at the University of Utah for support of a Program Project Grant (PPG) on the genetics and consequences of nicotine addiction. The broad objective of this PPG is to systematically dissect the genetic and molecular mechanisms of addiction and to determine the role of nicotine in the devastating clinical conditions caused by cigarette smoking, identifying specific facets that can ultimately be manipulated to prevent and/or effectively treat this devastating affliction. The thematic hypothesis being tested is that the susceptibility to both nicotine addiction and its consequences has underlying genetic components. In this hypothesis, nicotinic acetylcholine receptors (nAChRs) are critically involved in initiating the determining susceptibility to addiction and the consequences of cigarette smoking, including the dysregulated inflammation and abnormal repair that lead to chronic obstructive pulmonary disease (COPD). The hypothesis will be addressed by combining studies of candidate gene and linkage analysis using the powerful Utah family database and a well-established COPD database with studies using mouse genetics and biology. The studies are designed to generate new knowledge that will improve our understanding of the genetics of addiction and its consequences. In the PPG, productive established investigators with
58 Nicotine
excellent track records of interaction have combined to direct three projects and four cores. Each project addresses novel mechanisms and is oriented around the central theme. Each project is supported by new preliminary data that document the importance and feasibility of the proposed studies. We believe that the proposal offers the special advantages of established research programs, proven multidisciplinary collaborative interactions and a rich environment for productive basic and clinical research. By orienting the proposal around the genetics of addiction and its consequences, all three projects interact and intrinsically reinforce each other in almost every phase of their studies. The "intellectual structure" of the PPG is as follows: Project 1, combines the use of unique patient populations with "state of the art" techniques for genotyping and large scale nucleotide sequencing to investigate the genetics of nicotine addiction in humans. Project 2 complements the studies of Project I by delineating the genetic mechanisms that contribute to the formation and maintenance of tolerance to nicotine through nAChRs using well-characterized inbred mice and gene-targeting approaches. Project 3 uses the genetic approaches employed in Project I and animal models developed in the inbred mouse strains used in Project 2 to explore the role of nicotine in the pathogenesis of COPD and the genetic basis for COPD. An Administrative Core, an Animal Core, a Microarray Core and a Resequencing and Genomic Analysis Core support the three projects. The revised proposal has been restructured in response to the initial review and is much stronger. It offers established research programs coming together in multi-disciplinary collaborative interactions for productive basic and clinical research on an important societal problem. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETICS OF NICOTINE ADDICTION-EXAMINING ETHICS & POLICY Principal Investigator & Institution: Koenig, Barbara A.; Acting Associate Professor and Executive; Center for Biomedical Ethics; Stanford University Stanford, CA 94305 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2005 Summary: (provided by applicant): Studies are underway to examine the genetic factors contributing to smoking initiation, nicotine dependence, and inability to quit. Other studies use DNA array technologies to map nicotine-induced alterations in the brain. By providing a better understanding of the biological mechanisms involved in nicotine addiction, this unfolding body of genetic research is expected to fuel developments in pharmacogenetics, to create new genetic tests, and ultimately, to provide the basis for innovative strategies for smoking cessation and preventive interventions. Translating the results of genetic research into public health or treatment programs will require the resolution of a host of complex ethical, legal, social, and policy issues. The "geneticization" of smoking may cast additional stigma on smokers, or shift responsibility for addiction away from the cigarette (and the tobacco industry) and onto individuals' genetic make-up. Crucial issues will accompany testing: Who should be considered at risk? Will racial groups be targeted? How will access to services be affected? Should we use psychotropic drugs to prevent smoking? The proposed research will combine empirical investigation with ethical and policy analysis, employing a range of methods: systematic review of the scientific literature and of tobacco industry documents, interviews with stakeholders, ethnographic research at scientific meetings, and a multi-disciplinary, national Advisory Board. The project's empirical aims are to: 1) assess the state of scientific knowledge about the genetic basis of smoking behaviors and susceptibility to nicotine addiction, 2) anticipate and characterize clinical and preventive health applications based on this knowledge, and 3) examine the emergence
Studies 59
of a genetic understanding of smoking among key stakeholders in tobacco control. Informed by our empirical work, and in consultation with the project's Advisory Board, the ethical and policy aims are to: 4) delineate and evaluate the foreseeable impact of genetic explanations on existing smoking control policies, such as public health strategies and treatment programs, and, 5) identify and analyze key ethical, legal, and social consequences of a genetic understanding of smoking behaviors. The goal of the project is to provide policy makers with a clear understanding of the potential impacts and limitations of genetic research, ensure that genetics will integrate harmoniously in measures to reduce tobacco use, and contribute to the public policy debate about the genetics of addiction, by providing a comprehensive analysis of nicotine addiction - an illustration of the ethical complexities inherent in behavioral genetics research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETICS OF NICOTINE TOLERANCE: ROLE OF RECEPTORS Principal Investigator & Institution: Collins, Allan C.; Professor; Inst of Behavioral Genetics; University of Colorado at Boulder Boulder, CO 80309 Timing: Fiscal Year 2001; Project Start 30-SEP-1983; Project End 30-JUN-2004 Summary: The deleterious health effects that result from long-term tobacco addiction extract an enormous socioeconomic cost each year, yet astonishingly little is known about the causes of tobacco, or more appropriately, nicotine addiction. Nicotine use and/or treatment elicits a broad array of behavioral and physiological effects that presumably arise subsequent to the binding of nicotine to brain nicotinic cholinergic receptors (nAChR). Brain nAChRs are ligand-gated ion channels that are readily activated and desensitized by nicotinic agonists. Molecular approaches have identified 10 genes that encode for nAChR subunits. The mRNAs for some of these subunits are expressed in many brain regions whereas others appear to be expressed in only a few. The studies outlined in this proposal will attempt, using neurochemical and genetic strategies, to identify the subunit composition of nAChRs that make up several different ligand binding sites and regulate presynaptic processes such as ion flux and neurotransmitter release. These studies will make use of several null mutant (knockout) mice that have specific nAChR subunit genes disrupted. Other studies will assess the effects of chronic nicotine treatment on the number and function of mouse brain nAChRs. Experiments done with cell lines expressing neuronal-type nAChRs have demonstrated that chronic nicotine treatment elicits a permanent inactivation of receptor function. The chronic studies outlined in this proposal will evaluate whether a similar phenomenon occurs in mammalian brain, and whether this effect varies across brain regions and receptor subtype. The information provided will also be useful in testing the hypothesis that changes in nAChR number and function underlie tolerance and dependence on nicotine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENETICS OF VULNERABILITY TO NICOTINE ADDICTION Principal Investigator & Institution: Madden, Pamela A.; Assistant Professor of Psychology; Psychiatry; Washington University Lindell and Skinker Blvd St. Louis, MO 63130 Timing: Fiscal Year 2001; Project Start 25-MAY-2000; Project End 30-APR-2005 Summary: (Applicant's Abstract) Despite the public health significance of smoking, and evidence from adult twin studies for a strong genetic influence on smoking behavior (heritability estimates as high as 70%), there has been little research designed specifically
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to identify genes that contribute to risk of addiction to nicotine in humans. We propose a large-scale gene mapping study to identify specific chromosomal locations or candidate genes that have at least a moderate effect on risk. Families will be ascertained through panels of adult Australian and Finnish twins, and a sample of spouses of Australian twins, who have been identified as having a history of heavy smoking in earlier surveys. We will conduct diagnostic telephone interviews and blood drawing on probands, their full siblings and parents, to identify sibships with at least one affected sib pair (ASP) concordant for heavy smoking, and at least one living parent (target N=400 Australian, 400 Finnish families with approximately 600 ASPs from each). A 10cM genome-wide scan will be conducted using these families, with affected sib pair methods of linkage analysis used to identify candidate chromosomal regions suggestive of linkage. A transmission disequilibrium test approach will be used to test for candidate gene effects on nicotine dependence (DSM-IV nicotine dependence criteria and a-Fagerstrom Test for Nicotine Dependence score >= 4), and for fine mapping of candidate regions. Our study will have the advantage of having not only candidate alleles from trios (two parents plus nicotine dependent offspring), but also sibships with both nicotine dependent and non-regular ("unaffected") smokers. The availability of these within family controls will increase the robustness of our inferences. Candidate genes to be tested include CYP2A6, CYP2D6, and the dopamine D1 and D2 receptor genes. A database(without personal identifiers) will be established in St. Louis that includes genotype, diagnostic, and other pertinent information, a lymphoblast cell line repository will be established in St. Louis for cell lines obtained from Australian families; and a repository in Helsinki for DNA obtained from Finnish families, for distribution to qualified members of the scientific community. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GESTATIONAL DRUGS AND NICOTINE SELF-ADMINISTRATION Principal Investigator & Institution: Matta, Shannon G.; Professor; Pharmacology; University of Tennessee Health Sci Ctr Health Science Center Memphis, TN 38163 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): Nicotine is considered the gateway drug for other drugs of abuse, since nicotine exposure through cigarette smoking is one of the first drugs routinely self-administered by humans. Multiple factors are positively correlated with the initiation of smoking; one that recently has come to light is in utero exposure to the drug due to maternal smoking. In addition, alcohol rarely is consumed without the concurrent use of cigarettes, especially among women of childbearing age. Nicotine and alcohol each exert profound effects on brain development, resulting in alterations in 1) nicotinic cholinergic receptors, 2) dopaminergic content, receptors, and turnover, and 3) GABAergic functions, all of which are regionally- and gender-specific. The outcomes of such developmental aberrations on dopaminergic mechanisms that subserve addictive behavior are just now being investigated. Yet, the consequences of exposure to both agents have not been studied experimentally, despite strong epidemiological evidence for comorbid effects. Our goal is to identify neuronal mechanism(s) underlying the enhanced nicotine self-administration that we have observed in young adult rat offspring exposed to the combined effects of nicotine and alcohol (EtOH) during brain development. We have developed a non-invasive model for administering both drugs during the critical post-natal period of CNS development, which is the rodent equivalent of the third human trimester and the period of rapid brain growth. This will allow us to examine neuronal alterations resulting from full gestational drug exposure comparable to the human condition. We will characterize the behavioral outcomes of
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comorbid exposure by studying alterations in acquisition of nicotine self-administration in young adult offspring. Using receptor autoradiography, image analyses, and in vivo microdialysis, we will investigate changes in the dopaminergic and GABAergic cells of the mesocorticolimbic pathway. Since the addictive potential of a drug is correlated with its ability to affect the function(s) of neurons in this pathway, alterations due to gestational exposure to the combined effects of nicotine and EtOH could have profound effects on subsequent drug-taking behavior in the adult offspring Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HELPING AFRICAN AMERICAN LIGHT SMOKERS QUIT Principal Investigator & Institution: Ahluwalia, Jasjit S.; Chair and Director of Research; Psychology and Sociology; University of Kansas Medical Center Msn 1039 Kansas City, KS 66160 Timing: Fiscal Year 2001; Project Start 21-AUG-2001; Project End 31-JUL-2005 Summary: Cigarette smoking is the leading preventable cause of disease and death for all Americans. African Americans (AAs) continue to have a high prevalence of smoking, up to 50 percent among the urban poor. Enabling them to quit smoking is a national health priority. In the United States, smoking cessation efforts have focused primarily on heavy smokers and excluded light smokers (smoke s10 cigarettes per day). However, up to 50 percent of African American (AA) smokers are light smokers. Despite smoking fewer cigarettes a day, AAs extract more nicotine per cigarette smoked, and have higher tobacco- related morbidity and mortality. Using a nicotine inhaler may help smokers quit; however, it has not been studied among light smokers. Because light smokers constitute a large proportion of AA smokers, it is critical that cessation interventions, including pharmacological aids and counseling strategies, be developed to include AA light smokers. The primary aim of this study is to assess the efficacy of nicotine inhaler and motivational interviewing for smoking cessation among inner-city AA light smokers. This randomized, placebo-controlled study will be conducted at a communitybased clinic, Swope Parkway Health Center, in Kansas City, Missouri. The primary outcome of the study is biochemically-verified 7-day point prevalence abstinence from cigarette at 6 months. Secondary outcomes include: 1) 7-day point prevalence abstinence at 12 weeks and 1 year; 2) continuous abstinence at 12 weeks, 6 months, and 1 year; 3) change in the number of cigarettes smoked; 4) differences among groups in the effect of MI counseling based on participants' level of motivation; and, 5) differences among groups in the effect of the inhaler based on number of cigarettes smoked. This study will use a factorial design (2X2) in which 756 (189 in each arm) light smokers will be randomly assigned to one of four study arms: Tx1, Tx2, Tx3, and Tx4. Participants in Tx1 will receive placebo inhaler plus four health education sessions; Tx2 will receive placebo inhaler plus four MI counseling sessions; Tx3 will receive active nicotine inhaler plus four health education sessions; and, Tx4 will receive active nicotine inhaler plus four MI counseling sessions. Inhaler treatment (active or placebo) will be for 12 weeks. Recruitment and retention will be enhanced by use of monetary reimbursement for transportation and for completing study assessments, provision of attractive intervention materials, and a community advisory board. Post-intervention focus groups of quitters and non-quitters will assess the project's intervention components. Ultimately, we envision that the intervention, if efficacious, would enhance our understanding of smoking cessation and nicotine dependence, and could be used as a pre-packaged intervention for AA light smokers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HIGH DOSE NICOTINE EFFECTS IN RATS Principal Investigator & Institution: Pental, Paul R.; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, MN 554552070 Timing: Fiscal Year 2001 Summary: The aim of the proposed study is to evaluate the effects of high dose nicotine (HDN) infusion on nicotine self-administration (NSA) in rats. HDN safety and pharmacokinetics will also be studied. The long term goal of this work is to evaluate the potential of HDN as an adjunct to smoking cessation in patients refractory to standard therapies. Nicotine replacement therapy enhances smoking cessation rates, but most quit attempts are still unsuccessful. However, nicotine replacement therapy typically provides venous plasma nicotine concentrations that are substantially lower than those associated with smoking. Higher than usual doses of nicotine replacement, e.g. 2 nicotine patches at once, have been only equivocally successful in enhancing quit rates compared to usual doses, but even these higher doses do not provide the very high arterial nicotine concentrations associated with cigarette smoking. Whether even higher doses of nicotine (providing smokers with venous and arterial nicotine concentrations exceeding those experienced during normal smoking) would confer additional benefit is not known. Potential advantages of this level of HDN include more complete suppression of withdrawal, craving, and the rewarding effects of smoking. Hvpotheses to be tested are that 1) HDN suppresses the maintenance and reinstatement of NSA, 2) RDN is safe owing to the rapid development of tolerance to its adverse effects, 3) HDN efficacy can be augmented by combining it with the nicotinic antagonist mecamylamine, 4) the pharmacokinetics of HDN is similar to that of usual replacement doses, and 5) HDN reduces the formation of some carcinogens from tobacco. Studies will be performed in rats because the safety of administering HDN at the proposed doses to humans is untested. The effects of HDN on the maintenance of ongoing NSA and the reinstatement of nicotine responding will be examined. A range of both HDN doses and NSA doses will be used to establish dose-response relationships. The physiologic effects and safety of these treatments will be evaluated. HDN will be combined with the nicotinic antagonist mecamylamine to determine whether this combination is more effective than HDN alone, or better tolerated. The pharmacokinetics of HDN compared to usual nicotine replacement doses will be studied to aid in HDN dose selection. The formation of carcinogenic metabolites from the tobacco nitrosarnine NNK will be studied to determine whether this rate is altered when HDN and NNK are coadministered. Taken together, these studies will address the feasibility of using HDN as an adjunct to the initiation or maintenance of smoking cessation, and whether it is safe enough for testing in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HIGH DOSE NICOTINE PATCH THERAPY FOR SPIT TOBACCO USERS Principal Investigator & Institution: Ebbert, Jon O.; Mayo Clinic Rochester 200 1St St Sw Rochester, MN 55905 Timing: Fiscal Year 2002; Project Start 15-JUL-2002; Project End 30-JUN-2005 Summary: (provided by applicant): According to the 1999 National Household Survey on Drug Abuse, an estimated 7.6 million of the United States population 12 years of age and older (3.4%) currently use spit tobacco (ST). Long-term ST use increases the risk of developing oral leukoplakia, oropharyngeal cancer, and periodontal disease. Few studies of interventions for ST users have been conducted. A novel treatment approach
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for ST users employing existing pharmacotherapeutic agents is high dose nicotine patch therapy. Nicotine replacement therapy using standard dose nicotine patch therapy has not been shown to be effective for increasing tobacco abstinence rates in ST users. Our previous research in smokers shows that a high proportion of tobacco users have inadequate replacement of baseline serum nicotine levels with a standard nicotine patch dose and that higher doses (up to 44 mg/d) reduce nicotine withdrawal symptoms and increase tobacco abstinence rates. Since total daily nicotine exposure among ST users may be higher than in smokers, we propose that high dose nicotine patch therapy will improve withdrawal symptom relief, be safe and well-tolerated, increase tobacco abstinence rates and increase the replacement of baseline serum nicotine levels in ST users. To test these hypotheses, we will conduct a 3-phase study in which 60 adult ST users will be randomized to placebo or 3 different nicotine patch doses (21, 42, or 63 mg/d) with monitoring in our General Clinical Research Center (GCRC). Withdrawal symptom data will be collected using an Electronic Diary (ED). All subjects will receive a behavioral intervention during participation in the study. This ROl pilot study will serve as the foundation upon which the Principal Investigator will build a line of research committed to the health promotion and disease prevention objectives of Healthy People 2000. Our goal is to reduce the prevalence of ST use and decrease the incidence of oropharyngeal cancer through the development of effective treatment options for ST users. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HPA AXIS ACTIVATION AND NICOTINE USE Principal Investigator & Institution: Friedman, Theodore C.; Assistant Professor; Internal Medicine; Charles R. Drew University of Med & Sci 1621 E 120Th St Los Angeles, CA 90059 Timing: Fiscal Year 2003; Project Start 05-JUN-2003; Project End 28-FEB-2006 Summary: (provided by applicant): Many smokers use cigarettes as a means to combat stress. Removal of nicotine without addressing the underlying physiological changes associated with nicotine use results in an unbalanced system that compels a return to smoking to alleviate the withdrawal symptoms. Some of the behavioral and addictive properties of nicotine appear related to its activation of the hypothalamic-pituitaryadrenal (HPA) axis that is intimately involved in the stress response. Acute administration of nicotine has been shown to stimulate ACTH and corticosterone/cortisol secretion in both rodents and humans. The stimulation involves central mechanisms and corticotropin-releasing hormone (CRH) has been implicated as the mediator, but not shown to be required for the effect of nicotine. CRH and, to a lesser extent, arginine vasopressin (AVP) mediate the stress response. AVP also has a role in mediating the effects of nicotine on the HPA axis, as AVP-deficient rats have a severe blunting of ACTH to a nicotine-challenge. The stimulation of the HPA axis by nicotine may mediate some of the physiological and behavioral effects of nicotine. Additionally, a bi-directional interaction between nicotine and the HPA axis has been formulated based on the finding that corticosteroids attenuate some of the physiological and behavioral effects of nicotine. Thus, initial stimulation of the HPA axis may lead the smoker to increase his/her nicotine intake in order to maintain the stimulatory effects of nicotine on the stress response. The addicted smoker attempting to stop nicotine intake goes into a mild, yet unpleasant condition of glucocorticoid withdrawal, making smoking cessation less palatable. Thus, we propose that activation of the HPA axis is an integral part of the nicotine addiction process and understanding how nicotine interacts with the HPA axis will provide a basis for the rational development of novel treatments
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for nicotine addiction. Many questions about the link between nicotine and the HPA axis remain. Is CRH necessary to mediate the stimulation of ACTH release by acute nicotine? What is the role of AVP? How does chronic nicotine use stimulate the HPA axis? How important is the negative feedback on the axis by glucocorticoids? Most importantly, how does blockade of some of the arms of the HPA axis affect nicotine intake? The availability of new specific nicotine receptor antagonists, AVP-receptor antagonists and the non-peptide CRH-receptor antagonist, antalarmin, provide powerful tools to answering these questions experimentally. Adrenalectomy (with and without corticosterone replacement) allows us to study the role of glucocorticoids in nicotine-induced stimulation of ACTH and nicotine self-selection. These experiments should clarify the role of hypothalamic factors and glucocorticoids in the nicotineinduced stimulation of the HPA axis. The use of glucocorticoid synthesis inhibitors or antagonists, antalarmin, or other CRH and/or AVP antagonists, may be helpful in smoking cessation programs in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HUMAN GENETICS OF NICOTINE ADDICTION Principal Investigator & Institution: Leppert, Mark F.; Professor; University of Utah 200 S University St Salt Lake City, UT 84112 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2007 Summary: (provided by applicant): Approximately 1/3 of the US population over the age of 15 smokes, a behavior that has enormous impact on mortality and morbidity. While about 35% of smokers annually try to quit, only 3% successfully overcome their addiction. Causes of nicotine addiction likely include a variety of genetic and nongenetic factors. Recent advances in genomic technologies and computerized analysis programs have made it possible to discover susceptibility genes for complex traits. The discovery of genes that contribute to the risk of nicotine addiction will accelerate future efforts toward effective treatment and prevention. Major strengths of this project include the large sample size and the complementary genetic designs (sib-pair linkage, pedigree linkage,and association studies). We propose to carry out genomic scans on 1000 sibling pairs and 20 large Utah families in order to provide ample power to detect susceptibility loci. In addition, we will test for association with single nucleotide polymorphisms (SNPs) in candidate genes. Candidate genes will be chosen based on positional linkage evidence, strong physiological rationale, and altered expression after nicotine exposure in mouse microarray analysis. Existing well-characterized samples of heavy smokers from ongoing Lung Health Studies in Utah and ongoing nicotine dependence studies in Wisconsin will be supplemented by ascertainment of additional heavy smokers, light smokers, and non-smokers from the Utah population. Subjects will be given state-of-theart assessments of nicotine dependence and withdrawal, in addition to other phenotype assessments. Structural modeling will be used for data reduction to define phenotypic factors for genetic analysis. This project takes advantage of existing resequencing, genotyping and analytic capabilities in the Department of Human Genetics. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HUMAN IMAGING STUDIES OF NICOTINE DEPENDENCE AND WITHDRAWL Principal Investigator & Institution: Potkin, Steven G.; Professor; University of California Irvine Campus Dr Irvine, CA 92697 Timing: Fiscal Year 2001
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Summary: Smoking is a major public health problem, but the mechanisms underlying nicotine dependence are still unknown. UCI Center investigators have identified personality characteristics of high and low nicotine-dependence susceptibility (NDS), and have developed predictive models of future smoking behavior. The focus of the proposed fluorodeoxyglucose (FDG) and fluoro-L-dopa (F-Dopa) Positron Emission Tomography (PET) studies is to link differences in NDS and nicotine-related behaviors with the effects of nicotine on brain functioning. By determining the changes in brain glucose metabolism with FDG PET in response to nicotine, we hope to elucidate the neuronal systems that underlie differential susceptibility to nicotine. We hypothesize that subjects of high NDS will experience a larger brain metabolic change in the "prefrontal system" (mesocortico- limbic system plus associated limbic thalamus) from nicotine challenge than low NDS subjects while performing an attentional task. We propose that the amygdala plays a key role in distinguishing subjects of high and low NDS and is activated to a greater degree in the low NDS subjects. We propose to study non-smokers and smokers with low and high NDS traits with the same nicotine challenge paradigm while performing an attentional and a provoked aggression task. We hypothesize that smoking cessation in high NDS subjects will be characterized by a greater alteration in prefrontal system activity and a corresponding decrease in F-Dopa uptake in striatum and orbital cortex than in low NDS subjects. Our PET approach is unique in its focus on individual differences in nicotine-dependence susceptibility as the key variable in understanding the rewarding effects of nicotine and the difficulties in smoking cessation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IDENTIFICATION OF FUNCTIONAL NACHR VARIANTS IN MICE Principal Investigator & Institution: Stitzel, Jerry A.; Assistant Research Scientist; Pharmacology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, MI 481091274 Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 31-MAY-2005 Summary: (Provided by applicant): It is the long-term objective of this proposal to identify inbred mouse strains that express functionally distinct isoforms of the neuronal nicotinic receptor subunits alpha3, alpha4, alpha6, alpha7, and beta2. These subunits were chosen based on their potential roles in mediating the dependence-causing actions of nicotine. Identification of functionally distinct nicotinic receptor isoforms will be initiated by mutation analysis of the exons of the genes that encode these receptor subunits. Approximately forty inbred mouse strains of distinct genetic origins will be evaluated in the mutation screen. Once the mutation screen identifies nicotinic receptor subunit isoforms in mice with amnino acid differences, the appropriate cDNAs will be generated. Subsequently, the variant nicotinic receptor subunit isoforms will be evaluated in vitro for their pharmacological and functional properties. These experiments will lead to the establishment of a catalogue of mouse strains with known variations in nicotinic receptor subtype functional properties. This catalogue of mouse strains will serve as an important additional resource to evaluate the role of the various nicotinic receptor subunits in modulating the dependence-causing actions of nicotine. It has been estimated that 25 percent of all premature deaths in the United States are due to tobacco use. Despite the widespread knowledge of the health risks of smoking, approximately 25 percent of adults in the United States continue to smoke. Among smokers, nearly 80 percent say that they would like to quit although less than 5 percent successfully do so. It is well established that nicotine is the major dependence-causing agent in tobacco and that the initial actions of nicotine in the brain are mediated by
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nicotinic acetyicholine receptors. However, which nicotinic receptor subtypes mediate the dependence-causing actions of nicotine is poorly understood. To date, only modest success, at best, has been achieved in resolving this issue. The mouse strain nicotinic receptor "function" catalogue that will result from the studies outlined in this proposal will add a valuable resource for addressing this issue. By elucidating which nicotinic receptor subtypes are critical for the establishment of nicotine dependence, more effective pharmacological strategies for smoking cessation may be developed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMMUNIZATION TO BLOCK THE EFFECTS OF NICOTINE Principal Investigator & Institution: Pentel, Paul R.; Professor of Medicine; Minneapolis Medical Research Fdn, Inc. 600 Hfa Bldg Minneapolis, MN 55404 Timing: Fiscal Year 2001; Project Start 01-FEB-1997; Project End 31-MAR-2003 Summary: The aim of this study is to evaluate the effects of a nicotine vaccine on nicotine pharmacokinetics and nicotine-induced behaviors in rats. The long-term goal of this work is to study the therapeutic potential of vaccination as a medication for the treatment or prevention of nicotine dependence. Previous work has shown that a nicotine vaccine can elicit high titers of nicotine-specific antibodies in rats, markedly reduce the distribution of nicotine to brain, reduce the pressor effect and prevent locomotor stimulation from a single dose of nicotine. The proposed study will extend these observations by examining the effects of immunization on the pharmacokinetics of repeated daily doses of nicotine, and on behavioral models of nicotine dependence. Strategies for enhancing the efficacy of immunization will also be explored. Hypotheses to be tested include: 1) Immunization reduces the distribution to brain of daily nicotine doses which simulate regular cigarette smoking. Parallel experiments will evaluate the effects of vaccination on nicotine pharmacokinetic parameters (elimination half-life, clearance) during chronic nicotine dosing. These experiments will help to assess the extent to which nicotine-specific antibody becomes saturated by nicotine with repeated nicotine dosing and the quantitative limits on its efficacy. 2) Immunization attenuates the acquisition, maintenance and reinstatement of nicotine self-administration. These experiments will assess both the efficacy of immunization and whether it is best suited to preventing the initiation of tobacco dependence, assisting in the cessation of use, or in preventing relapse. 3) Immunization prevents the development of nicotine dependence, as measured by signs of withdrawal after the termination of nicotine dosing. This experiment will complement the nicotine self- administration studies by providing a measure of whether immunization attenuates the negative effects of nicotine that reinforce smoking. 4) The efficacy of immunization can be enhanced by the concurrent use of the nicotinic antagonists mecamylamine or dihydro-beta-erythroidine (DHbetaE). Because they antagonize the actions of nicotine by different mechanisms, immunization and receptor antagonists should have additive blocking effects. 5) Immunization against nicotine can be accomplished even during concomitant nicotine administration. This would expand the clinical settings in which vaccination could be used. Together, these studies will help to understand the mechanisms and quantitative relationships underlying the effects of immunization on the actions of nicotine, and begin to delineate the clinical settings in which therapeutic efficacy could be anticipated. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: IN VIVO 31P-1H MRSI AND MRI BRAIN STUDIES OF NICOTINE Principal Investigator & Institution: Pettegrew, Jay W.; Director, Neurophysics Laboratory; Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260 Timing: Fiscal Year 2001; Project Start 29-SEP-2000; Project End 30-JUN-2005 Summary: (Adapted from applicant's abstract) Nicotine addiction underlies the widespread use oftobacco products. Epidemiological evidence suggests that individuals who begin smoking as adolescents have a higher probability of being life-long smokers than individuals who start smoking in their 20's or later. There is little data on the possible influence ofbrain developmentand aging onthe molecular and metabolic effects ofnicotine whichcould contnbutc to its behavioral and addictive properties. This studywill investigate the effect of acute administration of eithernicotine by patch or placebo to human volunteers (nonsmokers and dependent smokers;age ranges 14-20and 35-45 years) on measures of high-energy phosphate [phosphocreatine (PCr) and adenosine 5'-triphosphate] and membrane phospholipid metabolism [phosphomonoesters (PME) and phosphodiesters (PDE)] by 31P magnetic resonance spectroscopic imaging (MRSI) and on measures of N-acetylaspartate ( a putative measure of neuronal integrity), trimethylamines [glycerophosphocholine, phosphocholine, and choline], and creatine (Cr) (PCr+Cr) by 1HMRSI. Both short correlation time ( S-Tc) and intermediate correlation time (I-Tc) components of the PME and PDE resonances will be quantified. The PME (S-Tc) are precursors of membrane phospholipids and the PME (i-tc) are phosphorylated proteins. The PDE (S-Tc) are breakdown products of membrane phospholipids and PDE (I-Tc) reflect the number of synaptic vesicles in grey matter. The influence of subject age and smoking status on the molecular and metabolic responses to nicotine will be investigated. In addition, quantitative 1H magnetic resonance imaging (MRI) will be performed in order to correlate the metabolic findings with the percent gray matter, white matter, and CSF in the voxels of interest from which the MRSI data is obtained. Our 31 P-1H MRSI pilot data in human nonsmokers in two age groups (young-adult and middle-aged subjects) suggests nicotine-induced transient breakdown of membrane phospholipids to PDE (sTc) and then to PME(S-Tc). There also appears to be a nicotine-induced decrease in PDE(i-Tc) levels in grey matter which could be related to transient reduction in synaptic vesicles. The pilot data indicates more robust changes in response to nicotine in the young-adult nonsmokers than in the middle-aged nonsmokers and a nicotine-induced response in different brain regions for young-adult versus middle-aged nonsmokers. We propose to investigate these aspects of brain metabolism in humans using 31P-1H MRSI. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: INDIVIDUAL VARIATION IN NICOTINE SENSITIVITY IN HUMANS Principal Investigator & Institution: Perkins, Kenneth A.; Professor; Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260 Timing: Fiscal Year 2001; Project Start 01-FEB-1995; Project End 31-MAR-2004 Summary: Individual variation in sensitivity to drugs (i.e., acute responsiveness to drug effects) may help explain vulnerability to onset and persistence of drug abuse, including nicotine dependence. In the previous funding period of this research program, the results identified and characterized tolerance to nicotine in tobacco smokers, defined as reduction in functional sensitivity to nicotine due to smoking history. In this competing renewal, this line of investigation will be extended in two directions: 1) examination of
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genetic and personality (primarily novelty-seeking) factors that are associated with variation in nicotine responses and reinforcement; and 2) focus on an earlier point in the dependence process-initial nicotine exposure. Variation of this "initial" sensitivity to nicotine likely accounts for some of the differences in the reinforcing effects of nicotine upon initial exposure and, thus, smoking onset. Because nicotine's reinforcing effects likely are related to its dopaminergic actions, genes involved in moderating these actions may be critically important in understanding vulnerability to nicotine dependence. The primary genotypes to be examined involve variants on the SLC6A3 ("dopamine transporter" gene)--specifically presence ("-9") or absence ("-*") of the -9 repeat allele. Nicotine administration will be carefully controlled to allow determination of dose-response relationships for each genotype on acute subjective, behavioral, and physiological effects of nicotine (i.e. "sensitivity"), as well as on nicotine reinforcement (i.e. self-administration). Two hundred never-smokers will be examined, approximately half with each variant, instead of smokers in order to rule out confounds due to nicotine tolerance and withdrawal. It is hypothesized that nicotine sensitivity and reinforcement will be greater in never-smokers with the -* versus -9 alleles of SLC6A3. Because the personality characteristic of novelty-seeking may help clarify the influence of dopamine genotype, comparisons will be made between nicotine sensitivity and reinforcement as a function of novelty-seeking. Secondary analyses will examine responses as a function of DRD2 ("dopamine receptor density") genotypes and explore the possibility of genegene interactions. This research will be the first to comprehensively examine factors associated with individual variability in initial nicotine sensitivity and reinforcement (i.e., in nicotine-naive individuals). Results will provide directions for future research on vulnerability to tobacco dependence and for targeted efforts to prevent smoking onset. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INDIVIDUALIZING TREATMENT FOR ADDICTED SMOKERS Principal Investigator & Institution: Garvey, Arthur J.; Assoicate Professor; Oral Health Policy & Epidem; Harvard University (Medical School) Medical School Campus Boston, MA 02115 Timing: Fiscal Year 2001; Project Start 01-JAN-2000; Project End 31-DEC-2004 Summary: Nicotine replacement continues to be the most promising treatment to date for tobacco addiction. Many questions remain, however, concerning how to optimize the effectiveness of nicotine replacement therapies. A major issue is how to prevent relapse to smoking after a quit-smoking attempt. Relapse rates are disappointingly high (typically 75 percent-80 percent), even for those receiving nicotine replacement treatment. We have planned a study very different from previous studies of nicotine replacement. Our study will be guided by the basic concept that generally characterizes medical management of any disorder: individualization of treatment based upon physiological characteristics unique to each person. Our plan is to test the efficacy of a procedure for tailoring the degree of nicotine replacement to match the smoker's usual nicotine intake using nicotine patches. We will randomly assign 750 smokers to one of 5 treatment conditions. 300 subjects will be given individualized treatment to replace either 50 percent or 100 percent of their pre-quit cotinine levels (cotinine is a major metabolite of nicotine that provides a stable measure of nicotine intake). A key feature of this treatment procedure involves close monitoring of cotinine levels after cessation and subsequent adjustment of dose if necessary. An additional 300 smokers will be given fixed standard or higher-dose patches rather than tailored nicotine replacement. These smokers will provide a dose-response control condition, which will allow us to compare individualization of treatment with a simpler model involving just standard or
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higher-dose patches. A final control group of 150 subjects will be given only placebo patches, to allow comparisons with a no-treatment condition. Our central hypothesis is that those who receive tailored 100 percent replacement (i.e., matching their usual smoking nicotine intake with nicotine patches) will be the most likely to succeed in quitting. We will also measure relevant biological, behavioral, and withdrawal variables. These data will allow us to examine mechanisms by which greater nicotine replacement affects cessation rates, to study effects of greater nicotine replacement for important subgroups of smokers (e.g., women, depressed smokers, older smokers), and to investigate additional factors, besides degree of nicotine replacement, that may be related to abstinence or relapse. Results will provide a clear, definitive test of the hypothesis that matching the degree of nicotine replacement to usual nicotine intake improves cessation rates. If this hypothesis is supported, our findings will have major implications for the treatment of addicted smokers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INITIAL SUBJECTIVE REACTIONS TO NICOTINE IN YOUNG ADULTS Principal Investigator & Institution: Lessov, Christina N.; Psychiatry; Washington University Lindell and Skinker Blvd St. Louis, MO 63130 Timing: Fiscal Year 2002; Project Start 05-MAR-2002 Summary: This 12-month project is motivated by the hypothesis that individual differences in initial nicotine sensitivity in humans are associated with nicotine dependence vulnerability and are an important mediator of genetic influences on risk of nicotine dependence. This application combines (1) characterization of existing data on self-report reactions to first cigarette assessed retrospectively in a large adolescent female twin sample (Missouri Adolescent Female Twin Study, MOAFTS) and on subjective reactions to nicotine versus placebo administered by nasal spray to smoking experimenters (smoked fewer than 100 cigarettes lifetime) and measured in the laboratory (Nicotine Challenge Study); and (2) collection of new self-report data on subjective reactions to first cigarette and recalled reactions to nicotine nasal spray in order to assess validity of proposed measures of nicotine sensitivity data and the feasibility of collecting such data from genetically informative samples. If measures can be shown to have acceptable reliability and validity, to be strongly familial and to be associated with nicotine dependence vulnerability, this will lay the groundwork for including such measures in gene-mapping and other genetic studies of nicotine dependence vulnerability and will help identify potential key targets for smoking prevention and intervention. A series of individualized tutorials and formal coursework will provide necessary advanced research training in human behavior genetic of addiction to support this research plan. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: INTERACTION BETWEEN NICOTINE AND STRESS Principal Investigator & Institution: Sharp, Burt M.; Chair; Pharmacology; University of Tennessee Health Sci Ctr Health Science Center Memphis, TN 38163 Timing: Fiscal Year 2001; Project Start 31-MAR-1985; Project End 31-MAR-2004 Summary: (Applicant's Abstract) Cigarette smoking has been recognized as the most important source of preventable morbidity and premature mortality in the United States. Amongst the potential psychoactive agents in tobacco smoke, nicotine appears to be the one primarily responsible for maintaining and regulating tobacco use. Stressful
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environments appear to present cues that enhance smoking, and chronic smokers report that smoking may have stress-reducing effects. Experimentally, the effects of nicotine and smoking on CNS responses to stress in animals and humans are inconsistent. These differences suggest that the dose, duration, schedule of administration and nature of the stressor are important determinants of the interaction between nicotine and CNS responses to stress. The proposed studies will elucidate the effects of chronic selfadministered nicotine on the stress-responsive systems of the CNS, both neurohormonal (i.e., HPA axis) and neurotransmitter [i.e., CRH and noradrenergic systems (NE)]. These studies will determine how the responsiveness of these systems to stressors is modified by unlimited access to self-administered nicotine, focusing on the following three regions of the brain that are involved in important aspects of the stress response: hippocampus (HP), amygdala, and paraventricular nucleus of the hypothalamus (PVN). Using (I) in vivo microdialysis to measure local NE secretion, (ii) in situ hybridization to measure heteronuclear CRH RNA as an index of acute neuronal activity (and CRH mRNA for cumulative changes), and (iii) tyrosine hydroxylase (TOM) mRNA and protein to detect cumulative changes in the function of NE neurons, specific aim 1 will characterize the effects of chronic nicotine on CNS noradrenergic projections and CRH systems within the PVN, amygdala and HP; the HPA axis will be assessed further by measuring plasma ACTH and corticosterone. Nicotine-induced differences in NE secretion within these three regions will be linked to functional changes in the noradrenergic brainstem regions that give rise to these NE projections. Specific aim 2 will determine how stress-induced HPA activity and NE secretion is affected by nicotine self-administration. Experiments will characterize ACTH/corticosterone secretion and CRH neuronal responses in the PVN and amygdala to a battery of acute stressors; parallel studies will assess stress-induced NE release in the PVN, amygdala and HP. Specific aim 3 will identify mechanisms whereby nicotinic cholinergic receptors (NAchRs) in the HP and amygdala, in coordination with those in the brainstem, mediate the release of NE in the HP and amygdala. Experiments will clarify the role of alphabungarotoxin- sensitive NAchRs in these regions. In summary, these studies will provide a mechanistic understanding of how chronic exposure to nicotine affects pivotal neurohumoral and neurochemical mediators of the CNS response to stress. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INTRACELLULAR MOLECULES OF NICOTINE ADDICTION Principal Investigator & Institution: Hiroi, Noboru; Psychiatry and Behavioral Scis; Yeshiva University 500 W 185Th St New York, NY 10033 Timing: Fiscal Year 2001; Project Start 01-AUG-2000; Project End 30-APR-2005 Summary: Adapted from applicant's abstract): The molecular basis of drug addiction has recently been explored using knock-out mice. These studies have revealed that a number of molecules contribute to distinct aspects of addiction to stimulants, opiates, and ethanol. However, the molecular basis of nicotine addiction remains unclear despite the fact that addiction to nicotine and other drugs shares a common neuroanatomical basis. The transcription factor FosB and the protein phosphatase inhibitor DARPP-32 (dopamine- and cAMP-regulated phosphoprotein of 32 kDa) have been shown to be critical determinants for different aspects of behavioral responsiveness to cocaine in mice. These two intracellular molecules are unique in that their disruption makes animals more vulnerable to cocaine's behavioral effects. The present application is designed to test the hypothesis that these two molecules are also critical for nicotine addiction and that, if so, they play distinct roles in specific aspects of nicotine dependence. The experimental design is unique in three aspects. First, a number of
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behavioral models will be used to assess different aspects of nicotine addiction. They include tolerance, sensitization, conditioned place preference, withdrawal-associated conditioned place aversion, and self-administration. Second, an attempt will be made to assess the influence of genetic backgrounds on behavioral phenotypes. The dissimilar genetic backgrounds of knock-out and wild-type mice littermates have confounded the behavioral phenotypes of knock-out mice. Heterozygous mice will be repeatedly backcrossed to C57BL/6J mice to achieve a higher degree of similarity in the genetic backgrounds of knock-out mice and wild-type littermates (i.e., congenic mice). Third, anatomical analysis will determine the involvement of neuroanatomical adaptations in behavioral phenotypes. Based on the outcome of similar approaches to cocaine addiction, it is expected that these two genes contribute to specific aspects of nicotine addiction. If these molecules turn out to be important for vulnerability to nicotine addiction, this mouse study will provide a solid basis for genetic analysis of human addiction vulnerability. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LINKAGE AND CANDIDATE GENE STUDY OF NICOTINE DEPENDENCE Principal Investigator & Institution: Bierut, Laura J.; Director; Washington University Lindell and Skinker Blvd St. Louis, MO 63130 Timing: Fiscal Year 2001; Project Start 28-SEP-2001; Project End 31-AUG-2006 Summary: The goal of The Linkage and Candidate Gene Study of Nicotine Dependence is to detect, identify, and characterize genetic loci that predispose of protect individuals from the onset and persistence of nicotine dependence and that determine tobacco consumption. Heavy smoking (1 pack for 6 months or more) nicotine dependence (Fagerstrom Test for Nicotine Dependence greater than or equal to 4) affects about 10% of the population, and siblings of probands have a 40% risk of developing nicotine dependence (lambda2-3-4). 750 to 800 informative families will be recruited from HMO's (Detroit, MI; Minneapolis, N; St. Louis, MO). Roughly half of the families will be taken from the genetic epidemiology study (Project 1). Families with at least one heavy smoking nicotine dependent sibling pair will be interviewed and have their DNA sampled. Parents and other siblings who have smoked but may not be dependent will also be recruited for genetic analyses using family based association and quantitative linkage methods. A case control sample for association studies will be collected. Subjects will undergo a multi-domain assessment of cigarette use, nicotine dependence and related phenotypes. Our date set will include approximately 1200 independently counted affected sibling pairs, 800 discordant sibling samples on both parents; the remaining families are expected to have samples on one. Identify-by-state statistics that are robust to ethnic stratification can be used with these data. Candidate gene testing will be done on 950 cases and 650 controls and can be followed in 750 families using family based association tests. Two-stage genotyping using 400 markers spaced approximately 10cM will be conducted. A genomic survey will be conducted for chromosomal regions linked to nicotine dependence and related phenotypes. Sib-pair and variant component methods, quantitative and quantitative linkage analysis will be performed on the appropriate phenotypes. Areas suggestive of linkage will be followed up with additional genotyping. Candidate genes for nicotine dependence and related phenotypes will be examined. Potential candidate genes will be provided by Project 3. Bioinformatics will help guide candidate gene approaches by taking advantages of the publicly available results from human and mouse genome sequencing projects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: LONG-TERM POTENTIATION AND NICOTINE WITHDRAWAL Principal Investigator & Institution: Sumikawa, Katumi; Psychobiology; University of California Irvine Campus Dr Irvine, CA 92697 Timing: Fiscal Year 2002; Project Start 05-AUG-2002; Project End 31-MAY-2007 Summary: (provided by applicant): The long-term objective of this research is understanding how long-term nicotine use and subsequent nicotine withdrawal alter the normal functioning of synapses in the hippocampus. Cigarette smoking and acute and chronic administration of nicotine can enhance cognitive function, a property that has been linked with the continued use of cigarettes. Our studies have demonstrated that acute and chronic nicotine exposure facilitate the induction of N-methyl-Daspartate receptor (NMDAR)-dependent long-term potentiation (LTP; considered to be a cellular substrate for learning and memory) in the hippocampus. Following nicotine withdrawal, however, the threshold for LTP induction fluctuates and nicotine is no longer effective in facilitating the induction of LTP. These nicotine effects may represent the cellular basis of nicotine-mediated cognitive enhancement and unpleasant withdrawal symptoms, contributing to cigarette-seeking behavior. Nicotine enhances NMDAR responses in pyramidal cells via three different pathways, two involving disinhibition of pyramidal cells and the other involving activation of muscarinic acetylcholine receptors (AChRs). Our working hypothesis is that long-term nicotine exposure and withdrawal differentially alter these pathways, affecting NMDAR responses and thereby LTP induction. The proposed experiments will test this hypothesis by identifying altered pathways in hippocampi from chronic-nicotine-treated and withdrawn rats with combinations of electrophysiological, histochemical, and molecular biological approaches. The specific aims are to determine: (1) which pathways of nicotine action, leading to the enhancement of NMDAR responses, are altered, (2) if the normal functioning of a7 and non-a7 nicotinic AChRs on GABAergic interneurons are affected, (3) if feedforward GABAergic inhibition is altered, and (4) if muscarinic AChR-mediated signaling is affected. Results from these studies are expected to provide significant insights into mechanisms that underlie nicotine dependence, which may aid in the development of novel therapeutic strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MAINTENANCE TREATMENT FOR SMOKING CESSATION Principal Investigator & Institution: Killen, Joel D.; Associate Professor; Medicine; Stanford University Stanford, CA 94305 Timing: Fiscal Year 2001; Project Start 01-MAY-2001; Project End 30-APR-2005 Summary: (investigator's abstract): Four hundred adult smokers will be enrolled in the study. The primary goal is to compare 2 strategies designed to promote longer-term maintenance of smoking cessation. Each strategy will include an acute treatment phase and a maintenance treatment phase. All smokers will receive the same "Acute Phase Treatment." In this acute phase, all smokers will receive treatment for nicotine dependence that combines nicotine patch (21mg), bupropion (300mg), and relapse prevention training (RPT). During the acute phase, nicotine patch will be provided for a total of 8 weeks and bupropion and RPT will be provided for a total of 9 weeks. Following the acute treatment phase, participants will enter a "Maintenance Treatment Phase." During maintenance treatment, half of the participants (n=200) will receive an additional 16 weeks of therapy with bupropion. The other half (n=200) will receive matching placebo. Primary hypothesis: Participants who receive bupropion during the maintenance treatment phase will have a higher abstinence rate at l2mo follow-up than
Studies 73
participants assigned to receive matching placebo. Abstinence will be defined as a report of non-smoking (not even a puff) for 7 consecutive days prior to contact plus a saliva cotinine level below 20 ng/ml. With 200 participants per cell, we will have, in general, 80 percent power at a 2-tailed alpha of .05 to detect a difference in abstinence rates of at least 15 percent over a large range of success probabilities. Secondary objectives: we propose to genotype all subjects for polymorphisms at loci hypothesized to affect nicotine dependence and/or bupropion efficacy. These include CYP2D6, the serotonin transporter, the dopamine transporter, dopamine D2 receptor, and the dopamine D4 receptor. Analyses will examine whether polymorphisms at these loci moderate response to treatment. The proposed study will address several important gaps in our knowledge. First, our proposed study would be perhaps the first to evaluate the efficacy of an antidepressant medication as maintenance therapy in the treatment of nicotine dependence. Second, this study would be among the first to examine the efficacy of a treatment for nicotine dependence combining nicotine replacement and antidepressant medication. Third, to our knowledge this may be the first prospective trial of smoking cessation techniques in which genetic data are included as predictors of outcome. In general, this study will provide important practical information to the medical and health communities concerning the utility of longer-term therapy with antidepressant medication for smoking cessation and will advance our knowledge of the underlying relationship of nicotine addiction and depression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MAPPING DEPENDENCE
OF
SUSCEPTIBILITY
LOCI
FOR
NICOTINE
Principal Investigator & Institution: Li, Ming D.; Director of Bioinformatics; Pharmacology; University of Tennessee Health Sci Ctr Health Science Center Memphis, TN 38163 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2002 Summary: Despite increasing negative attitudes towards smoking and intensified public campaigns and legislation against smoking, virtually no further reduction in smoking has occurred in this country during the 1990's. According to the 1996 National Household Survey on Drug Abuse, an estimated 68.8 million Americans used tobacco products. Therefore, tobacco is one of the most widely abused substances. Many years of twin and family studies provide strong evidence for a genetic component to nicotine dependence. The heritabilities for nicotine dependence, estimated from twin, family and adoption studies, are in the range of 0.28 to 0.84, with a mean heritability of 0.53. Nicotine can increase dopamine release in the nucleus accumbens and the ventral tegmental area regions implicated in the rewarding properties of other addictive drugs. Taken together, these studies of heritability and the neurochemical basis for the rewarding properties of nicotine provide strong evidence that certain aspects of smoking are influenced by genetic factors. We hypothesize that a group of susceptibility genes increases vulnerability to nicotine dependence and that these can be detected by using a combination of a two-stage genome-wide screening and candidate gene approaches. In the first stage of genomic screening, approximately 1600 subjects from 400 nuclear families recruited equally from Caucasian and African American populations will be genotyped by 218 microsatellite markers spaced at approx. 20 cM throughout the genome, followed by model-free sib-pair linkage analysis. The potential regions of interest (P greater than 0.03) will be subjected to second stage genomic analyses by genotyping more markers (i.e., 2-5) on both sides of the region and by searching candidate genes within these regions. The same DNA samples will also be
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used for family-based association studies between the nicotine dependence and 10 plausible candidate genes, that are related to dopamine reward pathways or nicotine metabolism. The TDT or its variants will be used to test the significance. We expect that the completion of the proposed studies in this application will advance our understanding of genetic influences on nicotine dependence and may eventually allow targeting of novel prevention strategies to individuals at risk. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MAYO NICOTINE DEPENDENCE EDUCATION PROGRAM Principal Investigator & Institution: Dale, Lowell C.; Mayo Clinic Rochester 200 1St St Sw Rochester, MN 55905 Timing: Fiscal Year 2001; Project Start 01-JUN-2001; Project End 31-MAY-2006 Summary: (provided by Applicant) Tobacco use is associated with more than 400,000 premature deaths each year in the U.S. Thirty percent of all cancer deaths are due to tobacco. Treatment of nicotine dependence has been recognized as an important means of decreasing cancer deaths and effective intervention programs have been supported by the NCI since the late 1980s. Now, with more effective treatment offerings, an increasing number of pharmacologic agents, and financial resources from the recent settlements with the tobacco industry, the demand for education in nicotine dependence treatment is growing. The Mayo Nicotine Dependence Center, established in 1988, has a long history of very successful educational programs supported by an equally successful clinical program that has treated over 21,000 patients. However, the demand for our clinical and educational services, plus our desire to meet the needs locally and nationally, now requires additional funding. Building on our experience with a nationally recognized annual seminar on nicotine dependence treatment and program development and our successful internal medicine residency curriculum, we propose to provide a broad-based educational program including one-day workshops to train health care professionals in the USPHS Clinical Practice Guideline - Treating Tobacco Use and Dependence recommended intervention program, intervention training for physicians in training, continuation of our three and one-half day CME seminar, extended CME seminar specialty training for health care professionals who desire additional training, and a three month practicum in Nicotine Dependence for Master's candidates. We will also collaborate with The Mayo Medical School, The Mayo School of Health-Related Sciences, and The Mayo Graduate School to strengthen the nicotine dependence treatment curriculums of health professionals in training. All of the programs will be carefully evaluated for efficacy and quality improvement. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MEASURING DEPENDENCE AND WITHDRAWAL IN TEEN SMOKERS Principal Investigator & Institution: Colby, Suzanne M.; Ctr for Alcohol & Addict Studs; Brown University Providence, RI 02912 Timing: Fiscal Year 2001; Project Start 25-SEP-1998; Project End 31-JUL-2003 Summary: (Applicant's Description) Tobacco smoking by adolescents poses a major health threat, with 90% of adults having initiated smoking before the age of 18. Research with chronic adult smokers has demonstrated certain aversive effects of nicotine abstinence which have been implicated in maintenance of smoking among adults. Little is known about the characteristics, intensity, or relevance of nicotine withdrawal among adolescent smokers. The primary objective of this research is to measure the
Studies 75
physiological and psychological characteristics of nicotine withdrawal among adolescent smokers and to assess the relevance of these measures in predicting subsequent difficulty quitting smoking. In the proposed study, adolescent smokers (ages 13-17) will be recruited from a primary care setting to participate in a 3-session experimental protocol designed to assess nicotine withdrawal under carefully controlled laboratory conditions. Measures will include: a cognitive performance computerized test battery, negative affect and reactive irritability, smoking cue reactivity, and caloric intake. During session I, baseline assessments will be completed with no deprivation from nicotine. During session 2, assessments will be repeated after overnight abstinence from nicotine. In session 3, assessments will be re-administered after participants have resumed smoking at their baseline level. Immediately following session 3, a brief smoking intervention will be delivered. Follow-up assessments will occur in person at 3 and 6 months later, to measure smoking outcome. Measures of nicotine withdrawal effects (changes from session 1 to 2) and withdrawal relief effects (changes from session 2 to 3) will be evaluated and validated against: (1) baseline measures of tobacco use history, current intake levels, nicotine dependence, and motivation to quit smoking; and (2) subsequent tobacco use and quit attempts at follow up. A pilot study is proposed for Year 1 of this application in order to determine the cognitive performance test battery components to use in the larger trial. This research will contribute the first: 1) assessment of withdrawal among adolescents that is not retrospective or subjective; 2) evaluation of objective withdrawal characteristics among abstaining adolescents under controlled conditions; and 3) prospective validation of withdrawal measures as they relate to subsequent smoking outcomes. Thus, it will provide a greater understanding of nicotine withdrawal as a maintaining factor of adolescent smoking, and thereby provide an empirical basis for enhancing smoking cessation approaches for youth. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISM OF NICOTINE INHIBITION OF APOPTOSIS Principal Investigator & Institution: Wright, Susan C.; Senior Scientist; Palo Alto Institute/Molecular Medicine Molecular Medicine Mountain View, CA 94043 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-MAR-2003 Summary: Apoptosis is a form of physiological cell death that is thought to be an important mechanism for the elimination of abnormal or transformed cells. It is also the form of death induced in cancer cells by chemotherapeutic drugs and gammairradiation. An agent which interferes with the process of apoptosis could potentially promote tumor formation as well as interfere with cancer therapies. Our previous studies demonstrated that nicotine inhibits cytokine and chemotherapeutic druginduced apoptosis of a ability of nicotine to inhibit apoptosis may promote tobaccorelated carcinogenesis as well as decrease the efficacy of cancer therapies. Our previous studies demonstrated that nicotine inhibits cytokine and chemotherapeutic druginduced apoptosis of a variety of tumor cell lines, including those types related to tobacco use. We hypothesize that the ability of nicotine to inhibit to inhibit apoptosis may promote tobacco-related carcinogenesis as well as decrease the efficacy of cancer therapies. The aims of this proposal are: 1) to further define the conditions under which nicotine inhibits apoptosis in tumor cell lines and in normal epithelial cells; 2) investigate the molecular mechanism in which nicotine obstructs the apoptotic pathway; 3) determine if nicotine will decrease the efficacy of chemotherapy in a mouse model. We will examine the effects of acuter high dose, chronic low dose exposure, and the reversibility of nicotine's ability to inhibit apoptosis in tumor cell lines and normal
76 Nicotine
lung epithelial cells. We will test the effects of nicotine on different inducers of apoptosis in tumor cell lines and normal lung epithelial cells. We will test the effects of nicotine on different inducers of apoptosis including ionizing radiation, chemotherapeutic drugs, and anoikis (enforced cell detachment). We will analyze the mechanism of inhibition with special focus on signal transduction pathways that have been implicated as negative modulators of apoptosis. Studies will analyze the effects of nicotine on expression of Bcl-2, protein kinase C activity, the mitogen activated protein kinase pathway, and the PI3-kinase/Akt kinase pathway. Mice bearing transplantable tumors will be treated with different chemotherapeutic drugs with and without coadministration of nicotine to determine if there is a reduction in the therapeutic effect. The results of these studies should increase our understanding of the mechanisms underlying development of cancer in cigarette smokers and in smokeless tobacco users. This investigation will also provide insight into the potential hazards of continued tobacco use in patients undergoing cancer therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISMS OF NICOTINE INDUCED IMMUNOSUPPRESSION Principal Investigator & Institution: Frazer-Abel, Ashley A.; Amc Cancer Research Center 1600 Pierce St Denver, CO 80214 Timing: Fiscal Year 2002; Project Start 01-MAY-2002 Summary: (provided by the applicant): Among the deleterious effects associated with the use of tobacco products is the suppression of the immune function. Preliminary data demonstrates that nicotine, and its major metabolite cotinine, inhibit the expression and activity of cyclin-dependent kinase 4 (Cdk4). The inhibition of Cdk4 by nicotine and cotinine presents a potential mechanistic link between tobacco use and immune system dysfunction; the repression of Cdk4 by nicotine and cotinine induces cytokine unresponsiveness leading to immune system tolerance (or anergy). Hypothesis: Nicotine and cotinine exert immunosuppressive effects principally by repressing Cdk4 gene transcription and by altering Ckl interact ions. These actions are transduced through nicotinic acetylcholine receptors, involving calcium signaling, calcineurin and NFATI. This hypothesis will be tested with the following specific aims (1) Determine the extent and the mechanism(s) of the nicotine and cotinine induced repression of Cdk4 expression and competence induction, (2) Define the signaling pathway, cell surface receptor(s), and intervening molecules involved in the nicotine and cotinine induced repression of Cdk4. Both effects at the protein level by immuno-blot, and RNA level by RNase protection, will be explored in primary human T cells, with additional techniques including, receptor antagonist, electrophorectic mobility shift assay and array analysis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MODAFINIL AND NICOTINE IN ADOLESCENTS: PHASE I TRIAL Principal Investigator & Institution: Martin, Catherine A.; Psychiatry; University of Kentucky 109 Kinkead Hall Lexington, KY 40506 Timing: Fiscal Year 2003; Project Start 15-JUN-2003; Project End 31-MAY-2005 Summary: (provided by applicant): NIDA Small Grant: This small grant application meets the funding priority: 1. Newer, less experienced investigator (PI). The applicant is in the end of the fourth year of a K08 entitled Drug Abuse, Pubertal Hormones, and AD/HD in Adolescence. This study will extend her work in the area of psychopharmacologic research in drug abuse in youth with Attention Deficit/Hyperactivity Disorder (AD/HD). This Phase 1 clinical trial will examine the
Studies 77
safety and efficacy of modafinil and nicotine, alone and in combination, on abstinenceinduced nicotine withdrawal in nicotine-dependent adolescents. Physiological, behavioral and subjective measures of impulsivity/inattention and depressive symptoms and other measures of nicotine withdrawal will be assessed in nicotinedependent adolescents (16-18 years) who smoke 10 or more cigarettes per day and who started smoking before age 15. This study is based on the observations that impulsivity/inattention and depressive symptoms are associated with nicotine use, onset, dependence, withdrawal, cessation, and direct effects. Modafinil is a promising pharmacologic agent for the modification of symptoms of impulsivity/inattention and depression and is purported to have low abuse potential. It is hypothesized that modafinil will selectively diminish withdrawal-induced increases in impulsivity and depressive symptoms and offset reductions in attention, and the magnitude of these effects will be greater than those seen with nicotine replacement. In addition, it is hypothesized that the combination of modafinil and nicotine replacement will have a greater effect on nicotine withdrawal symptoms, particularly the withdrawal symptoms related to impulsivity/inattention and depression than either drug alone. This study will provide pilot data for an R01 submission that will investigate whether modafinil might be useful in the prevention of nicotine use and in a comprehensive behavioral and pharmacologic treatment intervention for early onset adolescent nicotine users. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MODELING DEPENDENCE
BEHAVIORAL
TREATMENTS
FOR
NICOTINE
Principal Investigator & Institution: Lesage, Mark G.; Minneapolis Medical Research Fdn, Inc. 600 Hfa Bldg Minneapolis, MN 55404 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 29-SEP-2002 Summary: (provided by applicant) Current therapies for nicotine dependence have limited efficacy. As such, researchers have asserted that animal models should be developed further to more closely approximate clinical treatment conditions, with the prospect that more effective treatments will be discovered. Although nicotine selfadministration models in animals have been useful in understanding the behavioral and pharmacological mechanisms of nicotine abuse, they are limited in addressing certain features of treatment interventions in nicotine-dependent humans. One clinical behavioral intervention that has been widely successful involves reinforcing abstinence with alternative reinforcers. The purpose of this proposal is to extend the preclinical methodology of alternative reinforcement to more closely approximate clinical applications of this approach using nicotine self-administration assays. Differentialreinforcement-of-other-behavior (DRO) schedules, which involve delivering reinforcers for not engaging in a target response, have been shown to reduce behaviors maintained by nondrug reinforcers in animals and successfully applied in the treatment of a wide range of behavior problems in humans. In the present proposal, DRO schedules will be used to reinforce rats for not engaging in nicotine-maintained responding (abstinence) using an alternative nondrug reinforcer. The effects of DRO contingencies will be examined under a range of self-administration assays (i.e., maintenance, acquisition, and reinstatement) to determine the spectrum of conditions under which nicotine selfadministration can be reduced. Findings from the proposed studies will serve as preliminary data for an R01 grant proposal. The research plan for the ROI will include examining variables that may enhance the effectiveness of DRO contingencies and suggest more effective ways of applying alternative reinforcement in clinical interventions. In addition, given that combined pharmacological and behavioral
78 Nicotine
interventions are most effective in treating nicotine abuse, another aim of the ROI proposal will be to examine the effects of combining nicotine replacement with DRO schedules of alternative reinforcement. Such studies will provide a means to evaluate the therapeutic potential of medications as adjuncts to behavioral interventions for nicotine dependence and abuse of other drugs. The proposed techniques will also provide a platform on which to examine the neuropharmacological mechanisms mediating the separate and combined effects of alternative reinforcement and pharmacological interventions on nicotine-self-administration. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR APPROACHES TO NICOTINE ADDICTION Principal Investigator & Institution: Patrick, James; Professor and Head; Neuroscience; Baylor College of Medicine 1 Baylor Plaza Houston, TX 77030 Timing: Fiscal Year 2001; Project Start 01-JUL-1987; Project End 31-MAY-2003 Summary: Nicotine is a drug of abuse that presumably exerts its effects through its interactions with specific nicotine receptors in the brain. Chronic exposure to nicotine results in an increase in the abundance of nicotine binding sites in the brains of both rats and humans. We have discovered, cloned, and sequenced ten members of the gene family that encodes subunits of the neuronal nicotinic receptors. In this application we propose a means of using these clones to study the metabolism and regulation of the nicotine binding sites in the brain. This approach uses our cDNA clones as templates for the synthesis of the extracellular domains of each receptor subunit in bacteria and then uses these bacterially expressed proteins to generate antibodies in rabbits. Affinity chromatography on columns containing subunit specific peptides results in antibodies able to distinguish between the extracellular domains of each receptor subunit. These antibodies and radioactive peptides are used to create quantitative assays sufficiently sensitive to determine amounts of specific receptor subunits in milligram quantities of brain. We will use these assays to explore the metabolism of the nicotinic receptor and the mechanisms that produce the up-regulation of nicotine binding sites following chronic nicotine use. Our goal is to distinguish between the different mechanisms that might generate more nicotine binding sites. We will also use the antibodies in a more qualitative fashion to determine the location on neurons of nicotinic receptors of specific subunit composition. The long-term goal of this research is to understand how the location of the binding sites that are up-regulated during chronic drug treatment relates to the processes that lead to addiction. These experiments will address issues fundamental to nicotine addiction and to the cellular mechanisms that lead to dependence on the drug. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MOLECULAR BASES FOR EFFECTS OF NICOTINE Principal Investigator & Institution: Lukas, Ronald J.; Senior Staff Scientist; St. Joseph's Hospital and Medical Center 350 W Thomas Rd Phoenix, AZ 850134409 Timing: Fiscal Year 2003; Project Start 05-AUG-2003; Project End 30-APR-2008 Summary: (provided by applicant): The long-term goal of this project is to establish whether and how chronic nicotine exposure alters nervous system function. The project is based on the central hypothesis that extended exposure to nicotine induces longlasting changes in numbers and function of diverse nicotinic acetylcholine receptor (nAChR) subtypes. These effects have potential relevance for nicotine dependence, use of tobacco products, tobacco-related diseases, treatments to prevent, limit or cease
Studies 79
tobacco use, and therapies for neurological and psychiatric disorders. Preliminary findings suggest our hypothesis that chronic nicotine exposure causes both (i) a persistent inactivation of nAChR function and (ii) an increase in numbers of nAChR via two causally- and mechanistically-distinct, posttranslational processes. Dose- and timedependence of nicotine's effects are postulated to be nAChR subtype-specific, as are pharmacological profiles for other drugs acting to alter nAChR numbers and function. One principal aim of this multi-layered project is to establish effects of exposure to nicotine or related substances on function of diverse, human nAChR subtypes. The other principal aim is to determine effects of those agents on numbers of nAChR. For both aims, studies will involve alpha1 beta1 gamma delta- (muscle-type), (alpha3 alpha5 beta4- (autonomic), alpha4 beta2-(brain nicotine-binding), and alpha7- (autonomic or brain neurotoxin-binding) nAChR expressed naturally and/or heterologously by model cell lines. Time (onset of effects and recovery)- and dose-dependent effects of cell treatment with nicotine will be established. Time and dose profiles will also be obtained using other drugs alone or in combination with nicotine to assess whether they mimic or block nicotine's effects, nAChR functional activity will be quantified by electrophysiological recording and ion flux assays. Radioligand binding and immunoassays will be used to quantitate nAChR and to assess their subcellular distribution and metabolism. Chemical reactivity of nAChR and mutational studies will be among those used to establish mechanisms involved in effects of nicotine and other drugs. These studies are significant because they will provide new perspectives on sites and mechanisms of chronic nicotine action in the modulation of nervous system function. Insights will also be provided into molecular bases of nicotine dependence. Specific nAChR subtypes that are affected most powerfully by chronic nicotine exposure will be identified. Insights will also be provided into the kinds of drugs that block or mimic nicotine's actions. Collectively, this knowledge will benefit development of strategies to treat mood, cognitive, and other nervous system disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR BEHAVIORS/DROSOPHILA
GENETICS/NICOTINE-INDUCED
Principal Investigator & Institution: Heberlein, Ulrike A.; Associate Professor; Anatomy; University of California San Francisco 500 Parnassus Ave San Francisco, CA 94122 Timing: Fiscal Year 2001; Project Start 27-SEP-2001; Project End 31-AUG-2003 Summary: (provided by the applicant) Nicotine addiction is a major health problem in the world, yet little is known about the molecular and cellular mechanisms that mediate its addicting effects. The goal of this project is to develop "Drosophila melanogaster" as an animal model to identify the genes and signaling pathways that regulate acute sensitivity to nicotine, the development of tolerance, and withdrawal. For this purpose we plan to carry out a genetic screen for mutants that show aberrant behaviors upon acute and chronic exposure to nicotine. The acute effects of nicotine will be measured with assays for locomotion, geotaxis, and postural nicotine. Tolerance will be quantified as the change in acute responses caused by pre-feeding nicotine for several days. Mutants that show altered responses that are not accounted for by changes in sensory systems will be characterized molecularly. We also propose to develop assays to quantify withdrawal from chronic nicotine exposure. These include assays for general hyperactivity and startle responses to chemosensory and mechanosensory stimuli. Flies are easy and inexpensive to rear, and nearly a century of extensive analysis has provided innumerable and sophisticated tools for genetic and molecular analysis. These attributes, together with the high degree of evolutionary conservation and the relevant
80 Nicotine
neurochemical systems, allow us to carry out unbiased screens for novel molecules involved in nicotine responses, an approach that would be very expensive and laborious to implement in mammals. The genes identified in "Drosophila" should provide potential candidate genes and signaling pathways to be studied in rodent models and in human genetic studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOUSE-STRAIN SPECIFIC RESPONSES TO NICOTINE Principal Investigator & Institution: Rogers, Scott W.; Associate Professor; University of Utah 200 S University St Salt Lake City, UT 84112 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2007 Summary: (provided by applicant): Nicotine is the agent responsible for dependency to tobacco. But how does nicotine dependency, and the often-severe pathological consequences, develop in some, but not all, users? Nicotine exerts its effect(s) through specific ion-channel receptors termed nicotinic acetylcholine receptors (nAChRs). Because these receptors are the biological entry point through which nicotine exert its effects, understanding their expression and role in modulating cellular functions is imperative. However, the subunit composition and expression of native nAChRs is poorly defined as are the cellular mechanisms through which nicotine pre-conditions and modifies cellular responses. In this project we address these issues experimentally using genetically defined mouse strains with varying susceptibility to nicotine to define the distribution of key nAChR subunits in the brain. We will use microarray technology to define the impact of nicotine on transcription activation by the inflammatory cytokine, TNF alpha, and define proteolytic signaling cascades and responses that are altered by nicotine. Finally, we implement state-of-the-art gene-targeting and replacement methods to test directly the participation of key genes and/or pathways that are hypothesized to contribute to the genetic predisposition to nicotine as outlined below. Specific Aim 1. Strain-specific nAChR subunit distribution and expression. Hypothesis 1: The relative expression of nAChR subunit protein differs between inbred mouse strains. Hypothesis 2: Chronic nicotine (oral or smoking) alters region-specific nAChR subunit expression differently between inbred mouse strains. Specific Aim 2. Nicotine alters inflammatory transcriptional responses. Hypothesis: Strain-specific responses to nicotine pre-conditioning alter transcriptional response(s) induced by the pro-inflammatory cytokine, tumor necrosis alpha (TNFa). Specific Aim 3. Nicotine alters inflammatory post-transcriptional responses. Hypothesis: Strain specific responses to nicotine pre-conditioning modify protease activation and/or function induced by the proinflammatory cytokine, tumor necrosis alpha (TNF(x). Specific Aim 4. Strain specific zene-replacement of candidate genes. Hypothesis: Allelic replacement, through homologous recombination, of nAChR candidate gene polymorphisms from the C3H mouse into the C57BU6 will confer a novel phenotype on the recipient as defined in Specific Aims 1-3. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: MUTATION DEPENDENCE
SCREENING
OF
NICOTINE
AND
ALCOHOL
Principal Investigator & Institution: Todd, Richard D.; Professor of Psychiatry; Psychiatry; Washington University Lindell and Skinker Blvd St. Louis, MO 63130 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2007
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Summary: (provided by applicant): The long-term goal of this project is the identification of DNA sequence variations which predispose individuals to both alcohol and nicotine dependence. The sequelae of alcohol and nicotine abuse represent major health problems in the US and elsewhere including effects on the development of a variety of cancers, cardiovascular and lung diseases, as well as increasing the risk of suicide and other causes of mortality and morbidity. Many twin, adoption and family studies have demonstrated that there are important genetic contributions to the development of alcoholism and nicotine dependence. More modern studies demonstrate that a substantial proportion of this genetic liability is shared between these two disorders. A variety of physiological, biochemical, lesion and animal model studies have demonstrated the importance of ventral dopaminergic reward mechanisms in the self-administration and reinforcing characteristics of both of these substances. It follows logically, then, that variations in genes involved in the function or formation of these reward pathways may account for a portion or for all of the genetic liability shared by alcohol and nicotine dependence. The goal of the current application is to identify coding region and related DNA sequence variations in candidate genes associated with the dopaminergic reward pathways in individuals who have both nicotine and alcohol dependence. Using denaturing high-performance liquid chromatography (DHPLC) detection of sequence variation and standard and quantitative transmission distortion analytic approaches, three hundred nicotine and alcohol dependent individuals and their parents will be systematically tested for an association between DNA sequence variations in these candidate genes and the presence of alcohol and nicotine dependence. Finding such sequence variations will have important scientific and public health implications for understanding the genetic contributions to the risk for these disorders, for the development of novel pharmacological and other treatment approaches to these disorders and for the identification of individuals at risk for the development of these disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NALMEFENE IN NICOTINE AND ALCOHOL DEPENDENCE Principal Investigator & Institution: Mason, Barbara J.; Associate Professor; Scripps Research Institute 10550 N Torrey Pines Rd La Jolla, CA 920371000 Timing: Fiscal Year 2000; Project Start 29-SEP-1996; Project End 31-MAY-2004 Summary: APPLICANT'S ABSTRACT: The aim of the study is to determine the efficacy of oral nalmefene in reducing drinking and smoking in patients with concurrent nicotine and alcohol dependence. Opiate antagonists have demonstrated efficacy in reducing alcohol craving and consumption in alcoholics. Laboratory studies suggest opiate antagonist administration reduces symptoms of nicotine dependence. Nalmefene, an experimental opiate antagonist, was associated with reductions in both smoking and drinking in a 12-week double-blind pilot study of 23 patients with concurrent nicotine and alcohol dependence, with no increase in body weight or depressive symptoms. We propose to randomly assign 166 patients with DSM IV Nicotine and Alcohol Dependence to a double-blind, placebo-controlled 12-week trial of either a fixed daily dose of 80 mg nalmefene or placebo. All subjects will receive weekly individual coping skills and NCI smoking cessation behavioral therapy in keeping with good clinical practice and in recognition of the psychosocial aspects of these disorders. Drinking and smoking data will be collected from multiple sources including self-report diaries and time line interviews, collateral informant interviews, expired air carbon monoxide and breath alcohol levels, plasma nicotine/cotinine assays, liver function tests, and urine toxicology screens. Medication compliance will be assessed with MEMS
82 Nicotine
computerized medication bottle caps that record date and time of each use. Posttreatment follow-up interviews will be conducted at 3 and 6 months to determine smoking and drinking status and persistence of any treatment effects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUROBEHAVIORAL EFFECTS OF PRENATAL COCAINE AND NICOTINE EXPOSURE Principal Investigator & Institution: Sobrian, Sonya K.; Associate Professor; Howard University 2400 6Th St Nw Washington, DC 20059 Timing: Fiscal Year 2001 Summary: Multiple drug use among female cocaine abusers is common during pregnancy. Estimates are that 85% of pregnant cocaine users also smoke cigarettes; while use of alcohol, marijuana, amphetamine an tranquilizers decreases between the first and third trimesters, tobacco use does not. Despite the frequency of their combined use, there has been no systematic study of the effects of prenatal cocaine and nicotine exposure. However, use of either drug alone during pregnancy is linked with pregnancy complications, impaired growth and subtle behavioral abnormalities, maternal smoking is also a marker variable for long-term intellectual impairment. The proposed research will determine the behavioral sequelae of prenatal exposure to cocaine and nicotine, either alone or in combination, in offspring using a rat model developed in our laboratory. The working hypothesis is that exposure of the developing brain to nonteratogenic doses of these drugs will disrupt the structural and functional organization of the CNS, which in turn will alter behavior in the offspring. The model involves the daily subcutaneous administration of 20 mg/kg of cocaine and/or 5 mg/kg of nicotine by osmotic pump on gestation days (GD) 8 through 21. Both pair-fed and saline-treated dams will serve as controls. Plasma levels of cocaine, nicotine and their major metabolites will be determine in dams on GD 15 and mothers and pups at birth; dopamine and DOPAC levels will be assayed in several brain region in offspring at various ages. Using a split-litter design, males and females from the 5 prenatal treatment conditions will be tested in a variety of behavioral paradigms. A longitudinal (from 1 week to 15 months of age] approach will be used to: 1) identify the behavioral domains (cognitive, emotional/motivational and motor) affected by prenatal cocaine and nicotine exposure; 2) determine whether combined drug exposure exacerbates or ameliorates the behavioral effects of either drug alone; 3) investigate whether these changes represent a delay in the rat of development, a later appearing alteration in functional capacity of the adult, or an induction of premature senescence; and 4) assess the possibility of gender-specific effects. These experiments will provide some of the first longitudinal data on the effects of prenatal exposure to cocaine and/or nicotine on both male and female offspring, and should begin to establish a consensus about the nature of the behavioral abnormalities produce by gestational exposure to these two drugs. The use of a large battery of behavioral tests, and the choice of the prenatal exposure window and drug doses most frequently used will allow for the replication and extension of the work of several laboratories and facilitate the resolution of conflicting findings regarding the effects of prenatal exposure to either drug alone. As the behaviors targeted also reflect cognitive and/or performance deficits reported in the clinical literature, the outcome of this research may serve as a guideline for determining the relative risks of combined use of these two drugs during pregnancy to the offspring. The identification of deficits as transient of long-term and the domains affected may impact the choice of treatment options. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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•
Project Title: NEUROBIOLOGY OF NICOTINE REWARD AND WITHDRAWAL Principal Investigator & Institution: Markou, Athina; Associate Professor; Scripps Research Institute 10550 N Torrey Pines Rd La Jolla, CA 920371000 Timing: Fiscal Year 2001; Project Start 10-AUG-2000; Project End 31-MAY-2005 Summary: (Adapted from the Investigator's Abstract) Tobacco smoking, which is attributed principally to the addictive properties of nicotine, continues to be a worldwide problem of drug abuse that leads to significant medical costs. Research investigating the mechanisms underlying nicotine dependence may provide insights into the development of behavioral and pharmacological approaches to the treatment of nicotine dependence and tobacco smoking. Similarly to dependence on other drugs of abuse, it is hypothesized that both positive and negative reinforcement processes play critical roles in the development and maintenance of dependence on nicotine. This project focuses on these two aspects of nicotine dependence in rats by exploring the neurobiological substrates of both the positive reinforcing properties of nicotine and the negative affective aspects of nicotine withdrawal that are hypothesized to lead to further drug use (i.e., negative reinforcement, self-medication). The overall hypothesis is that GABAergic and glutamatergic processes in the forebrain neural circuitry called the "extended amygdala" are critically involved in nicotine dependence. The proposed studies will explore the neurochemical substrates of acute nicotine reinforcement by investigating the role of GABA and glutamate neurotransmission in the reinforcing effects of nicotine, using an intravenous nicotine self-administration paradigm in rats (Specific Aim 1). Studies will also explore the role of GABA and glutamate neurotransmission in nicotine withdrawal as assessed by elevations in brain reward thresholds and somatic signs of withdrawal (Specific Aim 2). Finally, Specific Aim 3 will explore the brain sites that comprise or are related to the "extended amygdala" where GABAergic or glutamatergic manipulations may precipitate the affective and/or somatic signs of nicotine withdrawal. Preliminary work has demonstrated clear dissociations between reward threshold elevations and somatic signs of withdrawal that may be mediated by different brain sites. The experimental approach of studying the effects of GABA and glutamate neurotransmission with the same pharmacological manipulations in both the acute rewarding effects of nicotine and on nicotine withdrawal provides a cohesive, focused and well integrated research plan. The innovative aspect of this work is the emphasis on exploring non-cholinergic substrates of acute nicotine reinforcement and of the various aspects of nicotine withdrawal, with emphasis on the affective/reward aspects of withdrawal and the "extended amygdala." Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NEUROBIOLOGY OF NICOTINE: HORMONES AND BEHAVIOR Principal Investigator & Institution: Mendelson, Jack H.; Professor; Mc Lean Hospital (Belmont, Ma) Belmont, MA 02478 Timing: Fiscal Year 2003; Project Start 20-MAR-2003; Project End 29-FEB-2008 Summary: (provided by applicant): This is a revision of a new application in response to PA-00-045 Neurobiological and Behavioral Research on Nicotine and Tobacco Components. Nicotine activates a4beta2 nicotinic receptors on mesolimbic dopamine neurons and increases extra cellular dopamine release. The indirect dopamine agonist effects of both nicotine and cocaine are thought to be important for their abuse-related effects. However, it is likely that dopamine is only one of a constellation of neurobiological systems that may contribute to nicotine abuse as well as to cocaine abuse. The role of the endocrine system in modulating the reinforcing effects of drugs is
84 Nicotine
poorly understood, but recent preclinical and clinical studies suggest that hormones may influence the abuse-related effects of cocaine, and these findings have led to novel approaches to treatment. Our preliminary studies indicate that both nicotine and cocaine stimulate anterior pituitary and adrenal hormones, and have similar pharmacodynamic and pharmacokinetic profiles. However, in contrast to cocaine, relatively little is known about the temporal relationships between nicotine-induced alterations in subjective states, hormone release patterns and increases in plasma nicotine levels, or how nicotine's effects may vary as a function of gender and/or menstrual cycle phase. We propose to conduct clinical studies of the acute effects of nicotine on the hypothalamic-pituitary-adrenal axis (HPA) and the hypothalamicpituitary-gonadal axis (HPG) in men and women who are daily smokers and are nicotine dependent (DSM-IV criteria). Women will be studied at the follicular and the mid-luteal phases of the menstrual cycle to determine if hormone fluctuations across the menstrual cycle influence nicotine's biological and abuse-related effects. The effects of two doses of nicotine and placebo on neuroendocrine, subjective and cardiovascular measures will be studied under double-blind conditions in an own control design. Nicotine will be administered by smoking in a procedure where puff volume, duration and frequency are measured and controlled. However, because other constituents of tobacco smoke may contribute to the effects of smoking, we propose to conduct parallel studies of intravenous nicotine. Examination of nicotine's effects on the endocrine system and correlated changes in subjective and cardiovascular measures will advance our understanding of the biological bases of nicotine's abuse-related effects, as well as its contribution to some reproductive disorders in women who smoke (e.g., early menopause and infertility). Clinical reports suggest that nicotine has anti-estrogenic effects, but there have been no comprehensive studies of nicotine's effects on the HPG axis. This question is important, because gonadal steroid hormones appear to enhance the abuse-related effects of cocaine in preclinical studies and may contribute to gender differences in cocaine's effects. We propose to study the temporal relations between nicotine's effects on gonadal steroid hormones, subjective effects and cardiovascular measures. An increased understanding of nicotine's acute effects on anterior pituitary, gonadal and adrenal hormones may suggest new strategies for the development of antinicotine medications as it has for cocaine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUROCHEMISTRY SCHIZOPHRENIA
OF
NICOTINE
DEPENDENCE
IN
Principal Investigator & Institution: Schiffer, Wynne K.; Neurobiology and Behavior; State University New York Stony Brook Stony Brook, NY 11794 Timing: Fiscal Year 2002; Project Start 06-JAN-2003; Project End 05-JAN-2005 Summary: (provided by applicant): Nicotine abuse is three times more prevalent in schizophrenic over non-psychiatric populations. It has not been established whether this phenomenon is inherent to schizophrenia or an effect of chronic neuroleptic treatment. Nicotine related increases in brain dopamine are associated with its abuse. Schizophrenic patients or animals given NMDA antagonists to putatively model schizophrenia, express an enhanced dopamine response to stimulants. This response is similar in many respects to that exhibited by animals chronically treated with the neuroleptic, haloperidol. We suggest that the pathology associated with dysfunctional NMDA receptors enhances excitatory input to brain dopamine systems. While chronic antipsychotic therapy might reduce inhibitory control over dopamine. Although different in origin, these imbalances may result in a similar. Amplified, response to
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nicotine, It follows that the enhanced response to nicotine may be regulated by either decreasing excitatory or increasing inhibitory neurochemical activity, respective of the underlying pathophysiology. We propose to examine this hypothesis with micro PET imaging techniques and microdialysis to explore the effects of a nicotine challenge on brain dopamine in pharmacologically altered biologically states. By chronically treating rodents with the NMDA antagonist, PCP, haloperidol, or both, we intend to examine the effects of haloperidol in the absence or presence of disease on the response to nicotine. In separate groups, we propose to use additional drugs to reduce excitatory activity with the glutamate antagonist, topiramate. Or increase inhibitory activity with the GABA agonist, gamma-vinyl GABA, prior to the nicotine challenge. We hope to guide the development of novel therapies for dual-diagnosis schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUROCOGNITION, NICOTINE & POLYSUBSTANCE ABUSE Principal Investigator & Institution: Ceballos, Natalie A.; Psychiatry and Behavioral Scis; University of Oklahoma Hlth Sciences Ctr Health Sciences Center Oklahoma City, OK 73126 Timing: Fiscal Year 2001; Project Start 15-AUG-2001 Summary: (Provided by Applicant) The use of legal and illegal psychoactive substances is an issue of major concern in our society. Although nicotine dependence, as well as concomitant use of nicotine and other drugs, is highly prevalent, particularly in treatment seeking substance abusers, the potential interactions of nicotine and other substances are not understood. This study is designed to examine the potential interactive effects of acute nicotine administration and chronic alcohol and/or stimulant abuse on brain electrophysiology in detoxified/abstinent substance abusers and community controls. Disentangling the interactive effects of these substances will lead to a better understanding of addictive processes and behavioral outcomes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NEURODEVELOPMENTAL SENSITIZATION
BASIS(ES)
OF
NICOTINE
Principal Investigator & Institution: Booze, Rosemarie M.; Professor and Endowed Chair of Behaviora; Psychology; University of South Carolina at Columbia Byrnes Bldg., Room 501 Columbia, SC 29208 Timing: Fiscal Year 2002; Project Start 28-SEP-2002; Project End 30-JUN-2007 Summary: (provided by applicant): Gender differences in response to psychostimulants have been reported both in animals and humans; however, the biological mechanisms which underlie these gender differences to psychostimulants remain for the most part, unexplained. The common observation is that females are more sensitive to psychostimulants, such as nicotine. Our hypothesis is: Gonadal hormones in adulthood and development act on dopaminergic systems, providing the underlying basis for the gender differences in behavioral sensitization produced by repeated IV nicotine administration. First, we will determine whether pharmacokinetic differences between the sexes result in higher levels of nicotine in the female brain. We have successfully developed a technically simple, economical and practical non-tethered technique for repeatedly administering IV nicotine to freely moving, group-housed rats. Detailed pharmacokinetic analysis has demonstrated rapidly peaking nicotine levels following IV dosing in rats, which is similar to that observed in humans, as opposed to SC or PO dosing. Using this clinically relevant IV rodent dosing model, we will determine
86 Nicotine
whether pharmacokinetic factors contribute to the increased sensitivity of female animals to the effects of nicotine. Second, we will determine whether gonadal hormones regulate the expression of gender differences in response to nicotine in adulthood. We will test the ability of gonadal hormones to modulate dopamine receptor responsiveness to chronic nicotine administration. Third, we will determine whether the brain organizational (neurodevelopmental) effect of the perinatal hormonal milieu mediates the gender differences in nicotine responsiveness. We have pharmacologically characterized a recently discovered unique dopamine receptor subtype (D3) which is localized to the striatum/nucleus accumbens region of the brain. We hypothesize that alterations in dopaminergic systems underlie the gender differences produced by repeated IV nicotine administration. Our long-term goal is to determine the role of the dopamine neurochemical system in gender differences following repeated IV nicotine administration. The ultimate goal of this research is to develop pharmacological interventions to assist in correcting the behavioral problems associated with chronic tobacco use in humans, and specifically to provide potential insight into effective gender-specific treatment strategies for smoking cessation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUROMAGING OF NICOTINE WITHDRAWAL Principal Investigator & Institution: Tanabe, Jody L.; Radiology; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, CO 800450508 Timing: Fiscal Year 2003; Project Start 20-SEP-2003; Project End 31-JUL-2008 Summary: (provided by applicant): Most smokers in this country attempt to quit because of concerns about health. However, more than half of those who smoke one pack per day or more fail to quit or even cut back on smoking. Contributing to relapse is the desire to alleviate withdrawal, which has been clearly established and related to nicotine. Withdrawal has two components: somatic and affective. Avoidance of negative affective symptoms is thought to play a bigger role in relapse than avoidance of somatic symptoms, yet little is known about the physiology or specific brain regions that mediate affective components of nicotine withdrawal. The mesolimbic dopamine system is involved in positive reinforcement, but its role in withdrawal is poorly understood. Furthermore, somatic withdrawal in animals cannot be equated with mood in humans. Localizing brain regions involved in withdrawal in humans will provide useful information for understanding mechanisms of and directing therapy aimed at preventing relapse. The training plan outlined in this proposal will give me the skills needed to become an expert in neuroimaging of substance abuse, specifically the effects of nicotine on the brain. I will train under distinguished scientific mentors known for their research on the biology and genetics of nicotinic receptors and behavioral pharmacology of substance abuse. The proposed work represents a qualitatively different phase in my research development that complements the skills I have already acquired in advanced MR neuroimaging techniques. At the end of this training period, I will be able to conduct independent research in neuroimaging of substance abuse. The scientific hypothesis tested by this research is that acute nicotine withdrawal will be associated with changes in cerebral blood flow in mesolimbic dopaminergic brain regions. The hypothesis will be tested using MR arterial spin labeling methods to measure changes in cerebral blood flow (CBF) during acute withdrawal and correlating these changes with mood. Three specific aims are: i) Do CBF measurements provide an in vivo marker for symptoms of acute nicotine withdrawal in smokers? ii) Does acute nicotine withdrawal involve dopaminergic system or non-dopaminergic regions? iii) Does nicotine replacement reverse the alterations in CBF during nicotine withdrawal?
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUROPROTECTION--NICOTINE, NEUROTROPHINS
CEMBRANOIDS,
&
Principal Investigator & Institution: Ferchmin, Pedro A.; Universidad Central Del Caribe Bayamon, PR 009606032 Timing: Fiscal Year 2002; Project Start 15-FEB-2002; Project End 31-DEC-2005 Summary: Nicotine was shown to be neuroprotective in different experimental models and in some epidemiological studies. The well-known health risk caused by nicotine use involves vascular damage. but almost no neuronal damage. Nicotine is an addictive drug that causes behavioral modifications and biochemical changes in the brain. Different schedules of nicotine administration produce distinct behavioral and physiological effects. We propose that some of these behavioral and physiological states correspond to different degrees or modes of nicotine-mediated neuroprotection or otherwise modified susceptibility to excitotoxicity. Nicotine is usually taken in by humans in a complex mixture. We described that cembranoids from tobacco and Caribbean corals inhibit the effect of nicotine. Recently, we found cembranoids in cigarette smoke. Therefore it is plausible that cembranoids play a role in the health effects of nicotine. Since nicotine is known to induce the synthesis of neurotrophins, this could explain part of the nicotine-induced neuroprotection. It is proposed here to use rats treated with different nicotine administration regimens to test behavior, neurotrophin, concentration and expression in several brain areas and susceptibility to NMDA toxicity of acute brain slices. In the last part of this project it is proposed to use immunohistological methods to study the distribution of neurotrophins and their mRNAs in brain sections. In addition, it is proposed to measure the effect of different nicotine pre-treatments on the extent of damage after experimental focal ischemia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NGF AND NICOTINE REGULATION OF NICOTINIC RECEPTORS Principal Investigator & Institution: Avila, Amy M.; Pharmacology; Georgetown University Washington, DC 20057 Timing: Fiscal Year 2001; Project Start 25-SEP-2001 Summary: The goal of the research outlined in the following proposal is to further investigate how neuronal nicotinic receptors are regulated by endogenous and exogenous factors, specifically nerve growth factor and nicotine. Neuronal nicotinic receptors play important roles in both the central and peripheral nervous systems, are implicated in several neruological disorders such as Alzheimer's Disease, and mediate the effects of the addictive drug nicotine. The specific aims of my research are to: (1) investigate how nerve growth factor and nicotine treatment alone and in combination affect neuronal nicotinic receptors in PC 12 cells. I will determine the effects of NGF and nicotine treatment on nicotinic receptor binding sites, function, and subunit protein expression. I will also determine the specific nicotinic receptor subtypes that are regulated by NGF and nicotine. (2) I will determine the mechanisms underlying the regulation of specific receptor populations in PC 12 cells with nicotine and NGF treatment. And (3) I will investigate the effects of nicotine and NGF treatment on native neuronal nicotinic receptors in rat adrenal gland primary cultures. I will then compare these results with those obtained from PC12 cells to determine how will the receptors in PC 12 cells model native tissue. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
88 Nicotine
•
Project Title: NICOTINE & MORPHINE EFFECTS ON DIABETES ONSET & COMPLICATIONS Principal Investigator & Institution: Obih, Patience O.; Xavier University of Louisiana Box 121-C New Orleans, LA 70125 Timing: Fiscal Year 2001 Summary: This study is undertaken to investigate the effect of drugs of abuse, morphine and nicotine on diabetes mellitus. Diabetes mellitus is the most common endocrine disease and consumes about 15% of annual health care expenditure in the United States. At the same time 36% of the population smokes cigarette and the opiates also rank high among the commonly abused agents. The long term goal of this study is to examine the hypothesis 1) Acutely or chronically administered nicotine or morphine accelerates the onset of diabetes. 2) Complications of diabetes worsen under the influence of chronically ingested nicotine/morphine. 3) the degenerative processes of diabetes will alter the receptor binding characteristics of morphine and nicotine receptor (ie. opioid receptors, nicotinic receptors and muscarinic receptors). We will examine these hypotheses with the following specific aims in mind: A) To evaluate the effect of morphine and nicotine on the onset of diabetes, rats will be treated with nicotine and morphine acutely or chronically and thereafter challenged with varying doses of streptozotocin (20, 40, 60 mg/kg)) intraperitoneally to induce diabetes. B) To examine the impact of morphine and nicotine on diabetic state, rats will first of all be made diabetic with intraperitonial injection of 60 mg/kg of streptozotocin (STZ). These diabetic rats will then be subjected to chronic administration of nicotine (8 weeks). Some groups of these rats will also be treated with insulin. The control will receive the vehicle. During the eight weeks, parameters to be monitored include: possible occurrence of diarrhea/constipation, body weight, fluid consumption, blood glucose level from an incision on the tail. At the end of the treatment period, animals will be killed by decapitation and parameters such as blood insulin and glucose level, by specific diagnostic kits will be measured, histopathology of the pancreas will also be examined. C) Radio ligand binding studies will be carried out to determine the receptor density of opioid receptors, nicotinic receptors, and muscarinic receptors in the treated and untreated rats. Examining the impact of attention since a significant number of US population and the world population suffer from addiction and may also have diabetes at the same time. The proposed study may increase the understanding of basic mechanisms of drug abuse in diabetes and may provide important practical information for developing new strategies for treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NICOTINE ADDICTION: ACH RECEPTORS AND SECRETION Principal Investigator & Institution: Fox, Aaron J.; Professsor; Pharmacological & Physiol Scis; University of Chicago 5801 S Ellis Ave Chicago, IL 60637 Timing: Fiscal Year 2002; Project Start 20-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): The addiction to nicotine results in a significantly shortened life span in millions of people and in billions of health care dollars spent every year in tobacco related illnesses. Although the mechanism of addiction is not understood there is a growing body of evidence pointing to the involvement of highaffinity neuronal nicotinic receptors (nAChR) in addiction. Our project will explore possible mechanisms that underlie nicotine addiction. Our studies will be carried out in adrenal chromaffin cells, which may be a primary peripheral target for nicotine. Chromaffin cells express neuronal nAChR similar to those in neurons; the subsequent
Studies 89
catecholamine release triggered by nicotine may be involved in the addiction process. Release of catecholamine may affect blood pressure and heart rate and may be involved in some of the adverse physiological changes seen in smokers. In addition, we will study physiological release mechanisms mediated by ACh (or nicotine). We have helped develop a new model system that will allow us to directly test the efficacy of neuronal nicotinic receptors in initiating neurotransmitter release. Similar studies will be carried out in chromaffin cells. The specific aims of this grant are: Aim 1 (Chromaffin Cells) Hypothesis: Activation of nicotinic receptors directly triggers or modulates neurotransmitter release. Nicotine levels in smokers are sufficient to produce significant desensitization of receptors, which alters release. Because nAChRs have a high permeability to Ca2+ our goal is to determine the importance of this Ca2+-influx pathway in triggering release using physiologically relevant applications of nicotine. These experiments will be repeated after both short- and long-term (20 mm. to 6 days) exposure to low levels of nicotine (100 -- 500 nM) similar to those observed in smokers. Because elevations of intracellular Ca2+ mobilize vesicles for release, we will try to determine whether low levels of nicotine (100 -- 500 nM) affect vesicular mobilization and the role of desensitization in this process. Aim 2 (mouse pheochromcytoma cells) Hypothesis: Activation of a variety of different nAChR can directly trigger secretion. My lab (in collaboration with Dr. Art Tischler's lab) recently identified a mouse pheochromocytoma (MPC) cell line that is secretion competent but which expresses no nicotinic receptors and few or no endogenous Ca2+ channels. We will transfect these cells with different types of nicotinic receptors to determine whether they can trigger secretion or mobilize vesicles and the mechanisms involved. Subunits that will be tested include a7 (alone), a3 b2, a3 / b4 and a4/b2. For these experiments we will employ cells that express no endogenous Ca2+ currents (determined by briefly depolarizing every cell). Physiologically, activation of nAChRs depolarizes cells and activates Ca2+ channels. In other experiments we will co-transfect nAChRs and the a1b/a2d/b3a(Ntype) Ca2+ channel subunits in order to study the synergy between these Ca2+-inf1ux pathways. This new aim is extremely exciting to us and is only possible because of the discovery of this remarkable cell line. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NICOTINE DEVELOPMENT
AND
ADOLESCENT
PREFRONTAL
CORTEX
Principal Investigator & Institution: Schochet, Terri L.; Psychiatry; University of Wisconsin Madison 750 University Ave Madison, WI 53706 Timing: Fiscal Year 2001; Project Start 01-SEP-2001 Summary: Addiction to nicotine is highly prevalent in the adolescent population, yet little research has examined the neurobiology of nicotine in adolescence. The brain continues to undergo developmental changes in adolescence. These changes are particularly evident in the prefrontal cortex, a region critical for risk assessment and impulse control. The changes produced by nicotine in adult rat models are well documented, and it is well known that nicotine exposure during early development causes neurobehavioral defects. However, the effects of nicotine on rat adolescent behavior and development are not well documented. Not only may nicotine exposure during this critical period of development have different effects on the brain, but may cause long-lasting alterations in the prefrontal cortex. The proposed research will investigate the sensitivity of adolescent rats to nicotine, the development of drugassociated cue conditioning to nicotine, and the gene-expression changes in adolescent prefrontal cortex. In addition, the long-term effects of nicotine exposure in adolescence
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on drug sensitivity will be examined. The underlying notion is that the substrate of the adolescent brain is fundamentally different than that of the adult brain, and the effects of nicotine addiction may be more lasting and profound than is currently known, particularly in regions involved in executive control of behavior, such as the prefrontal cortex. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NICOTINE AND BRAIN DEVELOPMENT Principal Investigator & Institution: Chen, Wei-Jung A.; Human Anatomy and Medical Neurobiology; Texas A&M University Health Science Ctr College Station, TX 77843 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-MAR-2005 Summary: The overall purpose of this proposal is to evaluate developmental nicotineinduced neurotoxicity. Despite the Surgeon General's warning concerning the harmful effects of smoking on the developing fetus, there is still a disturbing number of pregnant women who smoke during pregnancy. This proposal will utilize a rat model system to examine how and to what extent nicotine affects the developing brain. The proposal will test several hypotheses that are categorized into three Specific Aims. Specific Aim number 1 will test two hypotheses: 1) that nicotine exposure during all three trimesters equivalent will result in region-specific reductions in neuronal numbers in two important brain regions (hippocampus and cerebellum) in neonates and young adults; and 2) that the long-term brain deficits resulting from developmental nicotine exposure will be manifested through and correlated with specific behavioral impairments, spatial learning and parallel bars tasks, respectively. The exposure regimen used in Specific Aim number 1 is especially clinically relevant, since most pregnant women who smoke do so throughout pregnancy. Specific Aim number 2 will test two hypotheses: 1) that nicotine exposure during the third trimester equivalent (the brain growth spurt period) will lead to more severe neuronal loss than exposure restricted to first or first and second trimesters equivalent, and 2) that the cessation of nicotine exposure gestation will be beneficial to the developing brain. Specific Aim number 2 is important in addressing the questions regarding temporal vulnerability and the potential interaction between brain-regional specificity and temporal factors in mediating differential effects on nicotine-induced neuronal loss. Specific Aim number 3 will begin to address the question of mechanisms underlying nicotine-induced neuronal loss by testing the hypothesis that the application of specific neurotrophic factors (brain-derived neurotrophic factor [BDNF] and glial-derived neurotrophic factor [GDNF]) will attenuate nicotine-induced neuronal loss in an organotypic explant culture system. Specific Aim number 3 is the fist step to identify the involvement of specific neurotrophic factors as one of the underlying mechanisms for developmental nicotineinduced neuronal loss. The proposal will incorporate innovative in vivo and in vitro approaches to evaluate nicotine's toxicity during brain development, and many of the experimental techniques (artificial-rearing for third trimester equivalent exposure, 3-D stereological cell counting, organotypic explant culture system) proposed to be implemented in this proposal are novel to developmental nicotine research. The proposed studies will contribute to and broaden our knowledge of the harmful consequences from maternal smoking during pregnancy, provide a better understanding of the potential risk that may influence the severity of nicotine-induced brain deficits during different stages of development, and lead to a focus on mechanistic issues regarding developmental nicotine-induced neurotoxicity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NICOTINE AND CENTRAL ALPHA 2 ADENOCEPTORS Principal Investigator & Institution: Tizabi, Yousef; Howard University 2400 6Th St Nw Washington, DC 20059 Timing: Fiscal Year 2001 Summary: Nicotine, the primary psychoactive gent in tobacco, interacts with specific neurotransmitter systems including the noradrenergic system. Noradrenergic neurotransmission is mediated by several receptor subtypes including alpha2adrenoceptors. Nicotine-alpha2-adrenoceptors interactions may not only be responsible for some of the beneficial effects of nicotine, but may also be involved in nicotine dependence and nicotine withdrawal symptoms. Indeed, smoking cessation may be facilitated by clonidine, an alpha2-adrenoceptor agonist. However, clonidine's adverse effects preclude its use as a first-line treatment in smoking cessation. Various subtypes of alpha-2 adrenoceptors with distinct central distribution have been identified. Chronic nicotine administration results in increased density of cortical alpha2-adrenoceptors. However, it is not know whether alpha2-adrenoceptors in other discrete brain regions are also affected by nicotine. More importantly, no information is available on interactions between nicotine and specific alpha2-adrenoceptor subtype(s). This information is critical in identifying specific alpha2-adrenoceptor subtypes as potential targets for the development of novel agents in treatment of nicotine dependence and/or withdrawal. Thus, we propose to establish the specificity, time-course, duration, and dose-response relationship between nicotine administration/withdrawal and central alpha 2-adrenoceptors. Furthermore, since gender differences in the effects of nicotine and clonidine have been observed, both male and females will be studied. Nicotine will be administered to rats by osmotic mini-pumps. Autoradiography will be used to quantify alpha2-adreneceptor subtypes plasma levels of nicotine and cotinine (a major nicotine metabolite) will be determined by gas chromatography/mass spectrography and will be correlated with receptor binding data. These studies will significantly enhance our understanding of nicotine-alpha2-adrenoceptor interactions in the brain and will set the stage for further characterization of this interaction which may lead to novel pharmacotherapy in smoking cessation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NICOTINE AND NEUROPROTECTION IN PARKINSON'S DISEASE Principal Investigator & Institution: Rao, Jayaraman; Professor; Neurology; Louisiana State Univ Hsc New Orleans New Orleans, LA 70112 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Parkinson's disease (PD) is progressive neurodegenerative disorder. A combination of medical and surgical treatments has improved the quality of the lives of most PD patients. But the relentless progression of degeneration of the substantial nigra and consequent loss of dopamine in the basal ganglia ultimately leads to a severe debilitating state. Efforts to slow the disease even to a small degree will extend the life span and improve the quality of a patient's life and reduce the national burden of cost of care of PD patients.At present there are no drugs that can slow the progression of the disease. In this proposal it is hypothesized, that among all the available compounds, nicotine shows significant promise to be a neuroprotective agent for the degenerating dopaminergic neurons in PD. We will discuss evidence to support that: 1. Nicotine is neuroprotective in several models of neurotoxicity, 2. The neuroprotective effects of nicotine are mediated via several well established cell survival and anti-apoptotic molecular cascades, 3. The degenerating
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dopaminergic neurons in PD do show evidence of apoptotic death, 4. Nicotine is neuroprotective in animal models of PD, and 5. Nicotine's neuroprotective actions are accomplished by the activation of P13K/Akt antiapoptotic pathways by alpha4 - beta2 and aIpha7 - beta2 nicotinic receptors, which are abundant in the substantial nigra and striatum. A tentative research plan to conduct clinical trial using Transdermal nicotine patches is also proposed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NICOTINE CESSATION & SMOKING BANS IN ALCHOLISM TREATMENT Principal Investigator & Institution: Montini, Theresa M.; Scientific Review Administrator; Institute for Health Policy Studies; University of California San Francisco 500 Parnassus Ave San Francisco, CA 94122 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 30-JUN-2002 Summary: APPLICANT'S ABSTRACT: This project aims to discover two processes: the conditions under which nicotine cessation treatment programs will be integrated in substance abuse treatment programs; and, the conditions under which smoke-free policies will be successfully implemented and maintained in substance abuse treatment programs. This project has significant health relevance because there is a strong, positive correlation between heavy drinking and heavy smoking, and consumption of alcohol and tobacco have synergistic negative health effects that lead to increased risks of cancer, especially oral, esophageal, and laryngeal. Co-occurrence of smoking and excessive drinking has implications for alcoholism treatment. Prior empirical research has indicated that smoking cessation improves treatment outcome, and is positively related to the maintenance of sobriety. Currently there is no national data set that records the degree to which substance abuse programs offer nicotine cessation or are smoke-free, and how or why they do. Because we want to learn the reasons treatment programs incorporate nicotine cessation, and the process by which they adopt nicotine cessation, we will collect data via semi-structured, open-ended, in-depth interviews of a random sample (stratified by state) of 1% of the clinical directors of US substance abuse treatment programs. The clinical directors will be queried as to the process that led to their adopting nicotine cessation in their treatment program, or the reasons why they did not. The clinical directors also will be queried as to the process of implementing and maintaining a smoking ban in their treatment program, and how they succeeded or failed, or the reasons they are not smoke-free. The aim is to describe the state of treatment practice with respect to the role of nicotine cessation in alcoholism treatment; as well as compile the collective experiences on the implementation of a smoking ban that can be utilized by alcoholism treatment providers as they grapple with the challenges of health service provision. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NICOTINE COMORBIDITY
DEPENDENCE
TREATMENT
IN
PSYCHIATRIC
Principal Investigator & Institution: Williams, Jill M.; Psychiatry; Univ of Med/Dent NjR W Johnson Med Sch Robert Wood Johnson Medical Sch Piscataway, NJ 08854 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 30-JUN-2006 Summary: Nicotine dependence is very common among psychiatric patients and impacts clinical course, medication levels, and physical health of smokers. Unfortunately, there is a paucity of research for this subgroup of smokers and minimal
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treatment studies. The goals of this NIDA Mentored Patient-Oriented Research Career Development Award (K23) are to become an independent clinical researcher and create a program of research in the area of nicotine dependence and psychiatric comorbidity. This includes further training in Epidemiology and Quantitative Methods including research methodology, biostatistics and biocomputing, experiment design, process research and comorbidity issues. The UMDNJ-Robert Wood Johnson Medical School and the Rutgers Center for Alcohol Studies provide an excellent environment for developing research investigators. The primary mentor, Douglas Ziedonis, had extensive research experience, a NIDA Career Award, and is a leading psychiatrist studying nicotine dependence among individuals with schizophrenia. The research plan includes two studies. 1: Pharmacotherapy for Nicotine Dependence Among Psychiatric Patients. During a six-month study, schizophrenic smokers will be recruited into a double blind study comparing multiple doses of nicotine replacement pact .schizophrenics are believed to be more heavily dependent on nicotine, therefore, higher dose strategies and longer duration of treatment may yield greater quit rates. Study 2: Psychosocial Treatment for Nicotine Dependence Among Psychiatric Patients. Using NIDA stage a Behavioral Therapy approach, the specific aims of this study are to develop patient and clinical manuals, create adherence and rating scales and formalize a training program for clinicians and conduct a pilot study. Schizophrenics have unique disabilities in processing information and interpersonal communications that require specific and tailored therapies. Techniques from dual diagnosis treatment can be adapted for treating nicotine dependence and include aspects of social skills training, motivational enhancement therapy and relapse prevention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NICOTINE GENERATIONS
DEPENDENCE:
RISK
&
RECOVERY
OVER
Principal Investigator & Institution: Abrams, David B.; Director; Miriam Hospital Providence, RI 02906 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 29-SEP-2004 Summary: (Applicant's Description) The overall aim of this TTURC is to identify familial, early childhood and lifetime psychiatric factors that determine: trajectories of progression from smoking initiation to dependence; lifetime smoking patterns; the natural course of cessation; and response to treatment. Our proposed program of research combines a treatment/prevention imperative, a genetic epidemiologic approach, and a lifespan developmental perspective, sharing common scientific resources, to advance research on human nicotine dependence from basic mechanisms to applied interventions. We will use a synergistic combination of a community-based sample, prospective design, and a multigenerational family study to examine the major pathways to nicotine dependence, and to develop and validate a lifespan taxonomy of tobacco use and nicotine dependence phenotypes. The major goal is to identify modifiable risk factors that can serve as targets for prevention and that may be harnessed to enhance smoking prevention and cessation treatment success. We recognize that many such modifiable risk factors may act in concert with or against a substrate of genetic risks, and reason that a combined environmental and genetic/familial strategy is required both to clearly identify salient environmental agents and to prepare for studies of susceptibility genes. To this end, we propose to: l) To integrate multiple disciplinary perspectives and research methods front basic science to applications including (a) longitudinal natural history research (developmental epidemiology); (b) familial aggregation methods (genetic epidemiology); (c) human
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laboratory studies; and (d) intervention trials; (2) To adopt this lifespan and transgenerational genetic epidemiological approach to help understand risk factors for and causal pathways of: (a) progression of nicotine dependence among youth; (b) patterns of adult smoking; (c) the natural course of smoking cessation; and (d) response to treatment; (3) To document the potential utility and cost-effectiveness of a sustained "care management" approach to treating smokers that addresses smokers' risk profiles (from relatively uncomplicated to multiple comorbidities) with a range of treatment options that vary along dimensions of intensity and modality of intervention; (4) To collect and preserve DNA with the anticipation that, after refining phenotypic definitions, characterizing candidate genes (in other samples), and identifying the most heritable forms of smoking behavior, we may inform and conduct an efficient and productive strategy to identify susceptibility genes for nicotine dependence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RESEARCH
NICOTINE
DEPENDENCE--TAILORING
AND
PREFERENCE
Principal Investigator & Institution: Schneider, Nina G.; Psychiatry; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, CA 90024 Timing: Fiscal Year 2001; Project Start 01-JAN-1999; Project End 31-DEC-2003 Summary: The overall goal of the project is to significantly improve treatment of nicotine dependence. The health implications are considerable as smoking is a major cause of disease and death. Identifying individual needs in treatment and better defining mechanism in addiction (withdrawal; craving) can contribute to understanding other addictive behaviors. The specific aims of the project are: a) to test preference as a new approach for matching smokers to treatment; b) to better understand the relative role of various reinforcers in smoking and treatment. Two studies are designed to test these aims: the first is a crossover trial testing preference and withdrawal among 3 "acute" nicotine systems (nasal spray, nicotine inhaler, a new nicotine sublingual tablet); the second is a crossover trial of 4 combination treatments -3 combining a patch with each of the 3 "acute" systems and a double-active patch condition. Combining treatments (Study 2) can provide steady nicotine levels (patch) with an immediate means (acute) for handling cravings or crises; this bypasses the individual limitations of the patch (passive, slow) and of the acute systems (insufficient use). With excessive drop- out and relapse-producing slips plaguing current treatment, our aim is to determine what treatments individuals will use in practice and how different reinforcers (sensory, ritual, pharmacologic) contribute to compliance. We posit that knowledge of such biases will be essential for treatment matching and for proper use of any treatment. In essence, matching smokers to preferred treatments should greatly enhance success rates along with considerations of dose and pre-existing conditions. Several new scales will be tested: one which assesses withdrawal via anchored responding and a set of scales for testing preference with an ultimate aim of developing a tool for easily matching smokers to therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NICOTINE EFFECTS ON CEREBRAL BLOOD FLOW AND METABOLISM Principal Investigator & Institution: Domino, Edward F.; Pharmacology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, MI 481091274 Timing: Fiscal Year 2001; Project Start 01-MAY-1997; Project End 31-MAR-2004
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Summary: (Applicant's Abstract) There are three specific aims to this grant proposal. These are to determine the effects of nicotine in tobacco smoking amounts on (1 ) regional blood flow and (2) on regional glucose metabolism in the brains of adult cigarette smokers and (3) on males and females. Only cigarette smokers will be studied. State of the art imaging technology using positron emission tomography is available and ready to use with equipment already paid for at no extra cost to this grant. Nicotine will be administered by smoking a standardized research cigarette, as well as a nasal spray of a pure solution in order to determine whether the effects observed are due to nicotine alone or nicotine plus other chemicals in tobacco smoke. In addition, blood nicotine and cotinine concentrations will be measured and correlated with the induced functional brain changes. The cerebral blood flow study will compare regional cerebral blood flow following nicotine cigarettes and nicotine spray in 24 (12 male, 12 female) cigarette smokers, in a cross over, repeated measures design. Each subject will undergo two PET sessions scheduled at least one month apart. During each PET session five H-2-15-O scans will be run. During each of the two PET sessions, the first scan (baseline) will be followed by a scan immediately following inhalation of 5% CO2. The third scan will follow either nicotine placebo nasal spray or placebo cigarette administration, the fourth scan will follow a repeat nicotine cigarette/nasal spray administration, and the fifth scan will follow a repeat nicotine cigarette/nasal spray administration. These functional brain measures will be correlated with arterial and venous blood concentrations of nicotine measured by HPLC. The cerebral metabolic rate study will require that 24 (12 male, 12 female) tobacco smokers undergo two PET scans following injection with [18F]flurodexoxyglucose. Half of the subjects will be randomized to receive nicotine nasal spray and placebo nicotine nasal spray during two separate PET sessions scheduled at least a month apart. The other half will receive nicotine cigarettes and placebo cigarettes. The findings of this research will increase understanding of the effects of nicotine on the brains of normal male and female adults. This new information will make it easier to help understand why tobacco smoking is reinforcing and why it is so difficult to quit. The research proposed is both timely and accomplishable. Such information could lead to novel treatments for nicotine dependence by identifying the involvement of pertinent brain regions as well as possible pathways. This could set the stage for the study of nicotine effects in persons with cofactors for smoking, such as attention deficit disorder or mood disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NICOTINE EFFECTS ON THE ADRENAL MEDULLA AND BRAIN Principal Investigator & Institution: Tank, William A.; Professor of Pharmacology; Pharmacology-Physiology; University of Rochester Orpa - Rc Box 270140 Rochester, NY 14627 Timing: Fiscal Year 2001; Project Start 01-MAY-1990; Project End 31-JUL-2004 Summary: Adapted from applicant's abstract): This is the first revision of a competing renewal that received a score of 189 (29.8) from an associate professor at the University of Rochester, who has been studying tyrosine hydroxylase for many years. His research has principally concentrated on stress interactions, but he is now interested in investigating the complexities of nicotine effects on expression of this regulatory enzyme in catecholamine synthesis. Nicotine increases catecholamine release and biosynthesis in the adrenal medulla and in the brain. The effects on the adrenal medulla likely mediate nicotine's peripheral actions, e.g. on the cardiovascular system. However, brain effects on catecholaminergic systems might mediate some of nicotine's addictive properties. Tyrosine hydroxylase (TH) gene expression is enhanced in both the adrenal
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medulla and the locus coeruleus (LC) after twice daily injections of nicotine for 14 days; a single injection does not induce TH. Repeated nicotine injections result in repeated activation of several signaling pathways in catecholaminergic cells. Nicotinic antagonists do not completely block induction of TH by nicotine, suggesting that the induction may involve transsynaptic signaling pathways. Further, the induction of TH gene expression is hypothesized to involve both transcriptional and post-transcriptional mechanisms. The investigator will use two animal models (rat and transgenic mouse) and a tissue culture system (PC12 cells, a rat pheochromocytoma)to 1)Test whether the enhanced induction of TH gene expression observed after repeated nicotine treatment is mediated by transcriptional and/or post-transcriptional mechanisms; 2) Test which adrenal chromaffin cell receptors participate in the enhanced induction of TH gene expression which occurs after repeated nicotine administration; and 3) Test the hypothesis that the enhanced induction of TH in the LC is due to repeated stimulation of intracellular signaling pathways. by active nAChRs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NICOTINE INDUCED CEREBROVASCULAR DYSFUNCTION Principal Investigator & Institution: Mayhan, William G.; Professor, Vice Chair of Physiology; Physiology and Biophysics; University of Nebraska Medical Center Omaha, NE 681987835 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 31-MAY-2006 Summary: (provided by applicant) While cigarette smoke contains many toxic substances, it appears that nicotine may be responsible for the adverse effects of tobacco products on the cardiovascular system. Recent studies suggest that nicotine impairs nitric oxide synthase-dependent, but not -independent, dilatation of peripheral arterioles. While there is evidence, which suggests that smoking is a risk factor for the pathogenesis of cerebrovascular disorders, including stroke, mechanisms, which contribute to the development of cerebrovascular disorders remain uncertain. Thus, the central hypothesis of this application is that nicotine contributes to the pathogenesis of cerebrovascular abnormalities via alterations in cellularprocesses, which govern reactivity of cerebral arterioles. We propose two specific aims. In aim #1, we will determine the effects of nicotine on nitric oxide synthase-dependent and -independent responses of cerebral resistance arterioles. In addition, we propose to examine several potential mechanisms by which acute and chronic exposure to nicotine might influence nitric oxide synthase-dependent reactivity of cerebral arterioles. Our hypothesis is that nicotine impairs dilatation of cerebral arterioles via impairment in the arginine/nitric oxide syntheses biosynthetic pathway, and/or stimulation of oxygen derived free radicals. In aim #2, we will determine the effects of nicotine on reactivity of cerebral arterioles to activation of potassium channels. Activation of potassium channels plays an important role in the regulation of cerebrovascular tone in response to a variety of stimuli. We propose to examine the effects of nicotine on reactivity of cerebral arterioles to activation of potassium channels and examine potential mechanisms, which contribute to altered responses of cerebral arterioles during activation of potassium channels. Our hypothesis is that nicotine alters dilatation of cerebral arterioles in response to activation of potassium channels. In summary, studies proposed in this application will be the first comprehensive attempt to examine the effects of nicotine on cellular pathways, which govern reactivity of cerebral arterioles. Our studies will provide valuable insights into mechanisms by which nicotine may contribute to cerebral microvascular dysfunction, including stroke, observed in cigarette smokers and users of tobacco products. In addition, results of these studies may provide insights regarding
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possible therapeutic approaches for the treatment of nicotine-induced vascular dysfunction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NICOTINE INDUCED NEUROPLASTICITY IN THE CAROTID BODY Principal Investigator & Institution: Gauda, Estelle B.; Associate Professor; Pediatrics; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-JAN-2005 Summary: (Scanned from the applicant's description): Nicotine, a major component of tobacco smoke, is a neuroteratogen that binds to nicotinic cholinergic receptors on catecholamine-containing neurons and induces neuroplasticity. Catecholaminergic systems are vulnerable to the effects of prenatal exposure to nicotine since these systems develop early in ontogeny and have trophic influences on the development of multiple neuronal networks. Perturbations in neurotransmission in dopaminergic and noradrenergic neurons in the central nervous system induced by nicotine exposure are associated with postnatal morbidities which include, impaired cognitive function, attention deficit disorders and abnormalities in locomotion. Prenatal nicotine exposure also affects maturation of adrenal chromaffin cells resulting in altered stress responses. We present data that prenatal nicotine exposure increases catecholaminergic traits in peripheral arterial chemoreceptors that are involved in cardiorespiratory control. An increase in inhibitory catecholaminergic traits in peripheral arterial chemoreceptors may in part account for the striking epidemologic association between prenatal exposure to tobacco smoke and sudden infant death syndrome (SIDS). Infants born to smoking mothers have depressed hypoxic arousal responses, reduced respiratory drive, and blunted ventilatory responses to hypoxia. Similarly, animals exposed prenatally to nicotine have abnormalities in hypoxic ventilation, delayed autoresuscitation and increased mortality with exposure to hypoxia. Comparable to nigrostriatal neurons and adrenal chromaffin cells, peripheral arterial chemoreceptors are rich in catecholamines and express nicotinic receptors. Plasticity of neurons in the central nervous system induced by nicotine exposure involves regulation of catecholaminergic traits mediated by cAMP/calcium and the neurotrophins, basic fibroblast growth factor (bFGF) and brain-derived nerve growth factor (BDNF). Our preliminary data show that prenatal nicotine increases tyrosine hydroxylase (TH) mRNA expression, the rate-limiting enzyme for catecholamine synthesis, in peripheral arterial chemoreceptors. However, the mechanism for this effect is unknown. Yet, it is known that the expression of catecholaminergic traits in peripheral arterial chemoreceptors during development is neurotrophin dependent. In the current proposal, we hypothesize that nicotine exposure during development up-regulates catecholaminergic systems in peripheral arterial chemoreceptors via cAMP/calcium mechanisms and the induction of neurotrophins. Thus, using an in vitro rat model of peripheral arterial chemoreceptors, the goals of this proposal are to 1) determine the plasticity of peripheral arterial chemoreceptors induced by late fetal and early postnatal nicotine exposure and 2), elucidate the cellular and molecular mechanisms involved in this plasticity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NICOTINE MODULATION OF GENE EXPRESSION IN MICE Principal Investigator & Institution: Frank, Matthew G.; Psychiatry; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, CO 800450508 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2006
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Summary: (provided by applicant): Genetic factors play a considerable role in nicotine addiction. The present proposal addresses the molecular neuroadaptive processes that mediate the switch from initial nicotine exposure to addiction. Inbred mouse strains, which are highly sensitive to acute nicotine exposure, develop tolerance to chronic nicotine and provide a model for examining the mechanisms underlying the switch from acute nicotine exposure to addiction. C3H, DBA/2, and C57BL/6 mice represent low-, moderate-, and high-nicotine sensitive strains, respectively. Alterations in nicotinic acetylcholine receptors only partially explain the differential effects of acute and chronic nicotine in these strains. Nicotine modulates multiple neurotransmitter systems. The present proposal examines the molecular neuroadaptations in neurotransmitters that occur after acute and chronic nicotine exposure in C3H, DBA/2, and C57BL/6 mice. C3H, DBA/2, and C57BL/6 mice will be continuously infused with nicotine or saline for 6 hr or 10 days. Whole brain will be removed and mRNA phenotype assessed by gene microarray and expression changes validated by quantitative RT-PCR and in situ hybridization. Genotypic and phenotypic changes in mRNA expression in neurotransmitter biochemical pathways will be characterized. Determination of the differential effects of acute and chronic nicotine on gene expression may provide insight into the molecular neuroadaptations that underlie the switch from acute nicotine exposure to nicotine addiction in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NICOTINE MODULATION OF PARASYMPATHETIC CARDIAC NEURONS Principal Investigator & Institution: Mendelowitz, David S.; Associate Professor; Pharmacology; George Washington University 2121 I St Nw Washington, DC 20052 Timing: Fiscal Year 2003; Project Start 15-JAN-2003; Project End 30-NOV-2007 Summary: Fetal nicotine exposure is the highest risk factor for Sudden Infant Death Syndrome (SIDS) and yet despite substantial adverse publicity nearly one out of every four pregnant women smoke tobacco. Infants that succumb to SIDS have a severe centrally mediated slowing of the heart. During each respiratory cycle the heart normally beats more rapidly in inspiration and slows during post-inspiration, which is mediated largely, if not entirely, via respiratory modulation of parasympathetic cardiac vagal activity. Infants that succumb to SIDS are thought to have abnormal and perhaps exaggerated central cardiorespiratory interactions, and it has been speculated that a prolonged period of post-inspiration accompanied by a severe maintained decrease in heart rate, may be involved. Surprisingly, however, despite the physiological and clinical importance little is known about the pathways, transmitters and receptors that mediate respiratory modulation of parasympathetic cardiac vagal neurons in the medulla and how these interactions may change with fetal nicotine exposure. This project will directly test the unifying hypothesis that nicotinic receptors are responsible for the respiratory modulation of cardiac vagal neurons. We will also test the hypothesis that chronic fetal nicotine exposure exaggerates these cardiorespiratory responses. To accomplish these aims we will utilize a novel brainstem preparation that allows us to measure spontaneous rhythmic respiratory activity and evoked synaptic responses in cardiac vagal neurons. Our preliminary results show cardiac vagal neurons are inhibited during inspiration by increased inhibitory GABAergic and glycinergic inputs, and that the increases in GABA and glycinergic frequencies are mediated by activation of nicotinic receptors. In addition to the inhibitory inputs during inspiration, our preliminary results show cardiac vagal neurons are excited during post-inspiration by a glutamatergic pathway which may be modulated by nicotine. This work will not only
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address hypotheses fundamental to understanding the basis and mechanisms of cardiorespiratory rhythms in the neonatal rat that originate in the medulla, but will also suggest which receptors and processes could be altered by fetal exposure to nicotine which increases the risk of cardiorespiratory diseases such as SIDS. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NICOTINE REGULATION OF T CELL DEVELOPMENT Principal Investigator & Institution: Deluca, Dominick; Associate Professor; Microbiology and Immunology; University of Arizona P O Box 3308 Tucson, AZ 857223308 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JAN-2007 Summary: (provided by applicant): There is evidence for cross talk between the immune system and the equally complex and important nervous system. Immune system status is clearly influenced by status of the nervous system, and the opposite is also true. Studies by participants in this project have added to an evolving literature suggesting that the natural chemical neurotransmitter, acetylcholine (ACh), and the tobacco alkaloid, nicotine, have physiologically-relevant effects on immune system development and function. The diverse family of nicotinic acetylcholine receptors (nAChR) are targets for ACh and nicotine signaling. Studies by participants in this project indicate that specific nAChR subtypes are expressed by cells of the immune system, suggesting that these nAChR mediate effects of ACh and nicotine on immune system development and function. Based on these findings, this multi-investigator project will test the central hypothesis that nicotine and related ligands can regulate immune system development and function. The project will establish effects of nicotinic ligands on several important parameters relating to immune system function and development with a particular focus on T cell maturation. Work in the project will also identify and characterize known and/or potentially novel nAChR. Immune system components and thymic organ cultures from humans and mice will be used to characterize effects of nicotinic drug exposures on numbers and proportions of phenotypically-distinct T cell subsets and their expression of markers for positive/negative selection. Other studies will identify immune system nAChR subunits and subtypes and the cell subsets that express them with reference to developmental and drug treatment effects. Assays for cytokine production and for cytokine or recombinase activating gene expression using organ or cell culture samples will be conducted to identify mechanisms by which nicotine and related compounds affect immune cell development. Hypotheses to be addressed include: I) Nicotine regulates the development of T cells in the thymus. 2) Specific nicotinic ligands block or mimic nicotine's effects and reveal influences of endogenous signaling by ACh on T cell development. 3) nAChR involved in immune system development are expressed by T cells and their progenitors and/or by thymic stromal cells in developmentally-relevant patterns. 4) Immune system nAChR mediate their effects on T cell development by altering expression and/or secretion of cytokines and/or by altering expression of genes involved in T cell receptor rearrangements. One of the biomedically-relevant hypotheses of this project is that tobacco use and nicotine exposure affect immune system development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NICOTINE REPLACEMENT TREATMENT FOR PREGNANT SMOKERS Principal Investigator & Institution: Oncken, Cheryl; University of Connecticut Sch of Med/Dnt Bb20, Mc 2806 Farmington, CT 060302806 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 31-MAR-2007 Summary: (provided by applicant) Smoking during pregnancy is one of the most important modifiable causes of poor pregnancy outcomes in the United States. Unfortunately, the majority of women who smoke prior to pregnancy continue to smoke during pregnancy. Even with augmented behavioral interventions, smoking cessation rates in pregnancy trials rarely exceed 20 percent. These low quit rates may be due to inadequate treatment of the physical addiction to nicotine. Indeed, medications are firstline treatment for smoking treatment in non-pregnant smokers. However, little information is available on the safety or efficacy of medications to treat pregnant smokers. This proposal will examine the utility of one first-line medication, nicotine gum, as an aid to smoking cessation during pregnancy. The specific research aims of this project are: 1. To compare smoking cessation rates and smoking reduction among pregnant smokers who are randomized to receive 2 mg nicotine gum or a matching placebo; 2. To compare nicotine gum versus placebo on surrogate measures of maternal and fetal safety (i.e., overall nicotine and tobacco exposure), and birth weight at the time of delivery; 3. To examine which subjects benefit the most from the use of nicotine gum for smoking cessation during pregnancy. Subjects will be recruited from a prenatal clinic that serves primarily a low-income, minority population. Two hundred sixty-six pregnant smokers who smoke at least 5 cigarettes per day will be randomly assigned to receive a behavioral counseling intervention and either a 6-week course of 2 mg nicotine gum or placebo for smoking cessation followed by a 6-week taper. Primary outcome measures will be 7-day point prevalence cigarette abstinence, number of cigarettes smoked per day, saliva cotinine concentrations, and measures of tobacco exposure (i.e., carbon monoxide in exhaled air, and urine anabasine and anatabine) at 6 weeks after the quit date and at 32-34 weeks gestation. Birth weight will be obtained at the time of delivery. We hypothesize that 1. Pregnant smokers who are randomized to nicotine gum will have double the quit rates, and will reduce their smoking to a greater degree than subjects randomized to placebo; 2. Nicotine gum compared to placebo will reduce maternal cotinine levels, carboxyhemoglobin levels, and urine anabasine and anatabine levels. Birth weights will be higher in the offspring of subjects randomized to nicotine gum compared to placebo and will be negatively correlated with carbon monoxide and urinary alkaloids at 32-34 weeks gestation; 3. The odds of cigarette abstinence will be increased primarily in subjects who smoke at least 15 cigarettes per day. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NICOTINE SELF ADMINISTRATION IN MICE Principal Investigator & Institution: Khroyan, Taline V.; Behavioral Pharmacologist; Sri International 333 Ravenswood Ave Menlo Park, CA 94025 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-MAR-2004 Summary: (provided by the applicant) Nicotine plays an important role in maintenance of tobacco dependence. Nicotine self-administration has been studied in both nonhuman primates and rodents (i.e., Goldberg et al., 1981; Corrigall and Coen, 1989; Picciotto et al., 1998). To date, Nicotine self-administration studies in rodents have mainly used the rat as the species of choice. However, with the development of a complete genetic library in mice, the murine model is becoming an increasingly valuable
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tool for relating the genetic contributions to drug dependence. Thus, mouse selfadministration model has become an imperative tool to examine the genetic influences in drug addiction research. However, there has been only a few studies examining nicotine administration in the mouse. Initially, nicotine self-administration was established in mice that were partially immobilized since the intravenous portal was accessed through the tail, however, later studies used the jugular vein as the intravenous portal. Studies have also examined nicotine self-administration in mice that have had previous experience with other drugs of abuse (i.e., cocaine). Additionally, nicotine selfadministration has been examined in drug-naive animals using an extended 12-hour session. Thus, even though nicotine self-administration can be trained in mice, a mouse model using drug-naive mice and a more limited access schedule is needed (similar to that used to examine the rewarding effects of opiates and psychomotor stimulants). The following proposal will further develop nicotine self-administration in drug-naive mice that are not restricted in their movement and given a limited access testing period. Prior to examining nicotine self-administration in mice, the self-administration mouse model will be established in the PI's laboratory using cocaine as the experimental drug. Cocaine self-administration in mice has been well established, unlike nicotine, and will therefore provide a solid foundation for further work with nicotine. Following the establishment of nicotine self-administration, future experiments will examine the potential effects of a social stressor on nicotine self-administration as well as the role of gene/environment interactions using transgenic mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NICOTINE TOLERANCE: ASSOCIATIVE AND NONASSOCIATIVE Principal Investigator & Institution: Cepeda-Benito, Antonio; Psychology; Texas A&M University System College Station, TX 778433578 Timing: Fiscal Year 2001; Project Start 05-AUG-2000; Project End 31-MAY-2003 Summary: These experiments have three main goals. The first goal is to comprehensively test whether variables known to have a regulatory effect in the development and expression of associative and nonassociative tolerance to morphine's analgesic effects also are operative in the control of associative and nonassociative tolerance to nicotine's analgesic effects. The second goal is to study how differential genetic sensitivity to nicotine's effects influences the development of associative and nonassociative tolerance. The third goal is to investigate the role of nicotine-induced corticosterone release in the development of associative and nonassociative tolerance phenomena. This third question will be investigated in parallel with the first two goals. Five experiments will (1) evaluate the effect of number of conditioning trials in the development of associative tolerance to nicotine's analgesic effects, (2) examines the modulating effects of interdose interval (IDI) in the development and magnitude of associative and nonassociative nicotine tolerance, (3) establish the extent to which associative and nonassociative nicotine tolerance effects are retained in the presence versus the absence of extinction procedures, (4) attempt to obtain a nicotine dosedependent analgesic response in rat strains that are hypothesized to be differentially sensitive to nicotine, and (5) investigate the development of tolerance to nicotine's analgesic effects across rat strains that are differentially sensitive to nicotine. Experiment 1 will include independent groups of rats to study corticosterone changes as a function of exposure to the experimental manipulations. Corticosterone measures will examine how corticosterone fluctuates as a function of nicotine delivery in the presence and absence of drug predictive cues, and as a function of a placebo challenge in the presence of drug predictive cues. If these corticosterone analyses produce meaningful
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results, Experiments 2, 3, and 5 will also include concurrent measurement of corticosterone levels and analgesic responses. Experiment 5 will be conducted only if Experiment 4 yields the expected results. The present application does not request funding for the corticosterone measurements and Experiment 5; funding for these elements of the investigation will be sought through a competing supplemental application. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NICOTINE WITHDRAWAL, SMOKING & COGNITION: AN FMRI STUDY Principal Investigator & Institution: London, Edythe D.; Professor of Psychiatry & Biobehavioral; None; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, CA 90024 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 30-APR-2004 Summary: (provided by applicant) More deaths each year are attributable to nicotine dependence than to all illicit drug abuse combined. The causes and mechanisms of this disorder include social, physiological and cognitive components. While it is doubtful that effects on cognition are the primary reason for cigarette smoking, self-reports of why people smoke indicate that these effects are significant contributors. The broad objective of this work is to elucidate the neural circuitry involved in the cognitive effects of smoking and withdrawal. We will test how the activity of prefrontal brain regions that mediate cognitive control differs in nicotine abstinence and satiety. Cognitive control refers to brain functions that guide voluntary, complex actions. We also will test how patterns of brain activity related to cognitive performance differ in smokers and nonsmokers. Our long-term objectives are to provide information on how nicotine and smoking affect brain circuitry important to cognitive functions, and how these functions may differ in smokers and nonsmokers (either as effects of smoking or as etiological factors in nicotine dependence). Prior and ongoing studies have indicated that abstinence from smoking, nicotine administration, and even a history of smoking can affect performance on tests of cognitive control. Brain imaging studies with these tasks show activation of the dorsolateral prefrontal cortex (DLPFC) and the anterior cingulate cortex (ACC) as well as other brain regions. One such task is the Stroop Color-Word Interference Task, which requires focused attention and response inhibition while conflicting stimuli are presented. Performance of this task reliably activates ACC. Another test of cognitive control that shows possible effects of smoking is the N-Back Task, which requires working memory and generally produces activation of DLPFC. We will use functional magnetic resonance imaging (fMRI) to measure brain activation during performance of these two well-studied tasks. Our measure of regional activation in the brain will be change in magnetic resonance signal, representing relative hemodynamic change. We have two primary objectives. Our first specific aim is to determine the effects of smoking history and abstinence on brain function during performance of the N-Back Task and the Stroop Task. Smokers and nonsmokers will be tested with fMRI and cognitive activation. The smokers will be tested both in a state of satiety (after smoking ad libitum) as well as after 15-17 h of abstinence. Our second aim is to determine if smoking will reverse differences in brain activation and/or improve performance on the N-Back and Stroop tasks. Following each initial cognitive activation test session, both at satiety (after smoking ad libitum) and during abstinence, smokers will be allowed to smoke (ad libitum for 10 min) and will be re-tested. Nonsmokers, serving as controls, will be re-tested at corresponding times. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NICOTINE, ATTENTION, AND CONDITIONED AROUSAL IN PTSD Principal Investigator & Institution: Buckley, Todd C.; Psychology; Boston University Charles River Campus 881 Commonwealth Avenue Boston, MA 02215 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 29-SEP-2003 Summary: (provided by the applicant) This study is designed to investigate the relationship between nicotine intake, attention allocation, and anxious responding in heavy smokers diagnosed with chronic posttraumatic stress disorder (PTSD). Although there is much work on the effect of nicotine on affective responding in the general population, there is a paucity of such research on certain classes of psychiatric disorder that are characterized by high levels of anxiety. Such research is needed as several lines of investigation suggest that individuals diagnosed with PTSD evince rates of smoking more than twice that seen in the general population. They are also at risk for poorer health outcomes relative to comparable groups of non-PTSD individuals, possibly due to the comorbidity of poor health habits such as smoking. There is little research however, that attempts to understand the mechanisms by which smoking becomes so prevalent in this population. Current affect regulation models of nicotine have the potential to inform our understanding of the high comorbidity between smoking and this common psychiatric condition; however, research on the issue remains absent. To address this gap in the literature, the current study is proposing to examine the relationship between nicotine intake, attention allocation, and anxious responding in heavy smokers diagnosed with chronic PTSD. Utilizing a factorial design, heavy smokers with PTSD will be randomized to undergo either a neutral laboratory procedure or one known to elicit conditioned anxious arousal. Subsequent to the laboratory mood induction, subjects will smoke either high yield nicotine cigarettes or placebo (nicotine free) cigarettes prior to being randomized to either an attention allocation task or no task condition. Concurrent measures of autonomic reactivity (heart rate, skin conductance, and blood pressure) and self-report will be gathered as indices of anxious arousal elicited by study experimental conditions. Hypotheses regarding the manner in which nicotine interacts with attention allocation to environmental stimuli to bring about either anxiolytic or anxiogenic effects will be tested from the perspective of the theoretical model of nicotine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NICOTINE, DYSFUNCTION
OXIDATIVE
STRESS
AND
ENDOTHELIAL
Principal Investigator & Institution: Fitzgerald, Garret A.; Professor; University of Pennsylvania 3451 Walnut Street Philadelphia, PA 19104 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 31-MAR-2007 Summary: (provided by the applicant): Although the cardiovascular morbidity and mortality induced by cigarette smoking exceeds that attributable to lung cancer, the molecular basis of smoking induced tissue injury remains unclear. Considerable evidence supports a role for oxidant stress, and we have previously shown a dose response relationship between smoking and urinary isoprostane (iP) excretion, a reduction in iP excretion on quitting and suppression of elevated iPs in smokers with replacement of depleted vitamin C. Endothelial function is impaired in smokers, a harbinger of overt atherosclerosis and this defect is corrected by vitamin C supplementation. However, little is known of the effects of antioxidant vitamins on DNA and protein oxidation and we have some evidence that vitamin C may exacerbate DNA adduct formation. Interest has now developed in long term nicotine
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supplementation for smokers who cannot or will not quit. However, little is known of the chronic cardiovascular pharmacology of nicotine and several studies have shown impaired EC function in smokers switching to nicotine. The present studies are designed to investigate comprehensively the impact of nicotine on oxidative stress and its effect on EC function in humans, using novel approaches to the coordinate assessment of lipid peroxidation, protein oxidation and DNA modification in vivo. They will be complemented by studies of the impact of nicotine on oxidative stress and atherogenesis in mouse models employing novel approaches to proteomic analysis of the vasculature and circulating cells. Specific Aim 1: To assess the dose related impact of cigarette smoking on novel indices of lipid peroxidation, protein oxidation and DNA modification and on endothelial function in vivo. To assess the impact of vitamin C supplementation on these indices in cigarette smokers. To assess the impact of vitamin C supplementation on the disordered neutrophil protein expression found in smokers. Specific Aim 2: To assess the dose related impact of nicotine substitution on indices of oxidant stress, endothelial function and smoking induced neutrophil protein expression in smokers switched to nicotine. Specific Aim 3: To define the impact of chronic exposure to cigarette smoke on atherogenesis in the apobec-l/ LDLR double knockout (dko) mouse. To assess the effect of nicotine substitution on established smoking related atherosclerosis with and without continued smoke exposure and to assess the effect of nicotine de novo on atherogenesis in this model. Vascular tissues will be harvested to provide specimens for analysis of modified hyaluronan, fibrinogen and LDL in other projects. Proteomic analysis in the vasculature will assess the impact of disturbed flow and seek patterns analogous to those evident in human neutrophils in Specific Aim 1. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NICOTINE/NEUROENDOCRINE SIGNALING IN DEVELOPING LUNG Principal Investigator & Institution: Wuenschell, Carol W.; Ctr/Craniofacial Molec Biol; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, CA 90033 Timing: Fiscal Year 2001; Project Start 01-APR-1997; Project End 31-MAR-2003 Summary: Prenatal exposure to maternal smoking adversely affects the respiratory health of children even in the absence of postanatal passive smoking. Transplacental nicotine exerts developments effects on fetal lung in animals, including lung hypoplasia and hyperplasia of pulmonary neurodendocrine cells. Paradoxically, the lungs of smoking-exposed infants appear to be more mature at birth than those of unexposed infants. The cellular and molecular mechanisms underlying these prenatal effects of maternal smoking are presently unknown. The study will use culture of whole embryonic mouse lungs in chemically defined medium as a model system to study the mechanism of nicotine action in development lung. Preliminary data show stimulation of branching and expression of the genes encoding the peptide growth factor GRP and surfactant proteins SP-C and SP-A in nicotine-treated lungs. The effect on SP-C gene expression is blocked by the nicotinic antagonist d-tubocurarine. Further, the increase in SP-C gene expression is blocked an antibody directed against the reactive region of GRP. Thus, the effects of nicotine in this system are mediated by nicotinic acetycholine receptor (nAChR) subtype and GRP may be a mediator in the downstream pathway. The added observation that embryonic lung distal epithelial cells posses and partial neuroendocrine phenotype leads to his hypothesis; That nicotine alters the developmental program of the embryonic lung including expression of surfactant protein genes, through a mechanism involving nAChRs located on cells of the distal epithelium and stimulation of production of GRP by these name distal epithelial cells.
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The specific Aims are: 1) To characterize the effects of added nicotine on development of embryonic lung with respect to growth, branching morphogenesis, specific gene expression and differentiation of epithelial cells. 2) To determine the nature and location of the nAChRs mediating the developmental effects of nicotine in embryonic lung. 3) To test the role of GRP as a downstream mediator of nicotine effects by blocking strategies. The results of this study will provide insights into an aspect of normal lung development that has not previously been explored, as well as increasing our understanding of the mechanism of nicotine toxicity in developing lung and possible cancer risks from prenatal nicotine exposure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NICOTINE: COGNITION-AFFECT INTERACTIONS Principal Investigator & Institution: Gilbert, David G.; Professor; Psychology; Southern Illinois University Carbondale 900 S. Normal Carbondale, IL 629014709 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2006 Summary: (provided by applicant): The primary objective of this revised proposal is to characterize more fully when, how, and in whom nicotine modulates affect and attention to emotional stimuli. It is hypothesized that nicotine attenuates attentional bias to negative emotional stimuli and associative processing of such stimuli, thereby decreasing negative emotional states. This attenuation of negative attentional bias and associative processing by nicotine is hypothesized to result from nicotine's enhancing attentional and associative bias to positive and neutral stimuli that in turn compete with and inhibit negative affect-related processing. Nicotine-induced attentional and associative biasing is hypothesized to occur most strongly in situations where the frequency of negative stimuli is moderate or low and the subject has a significant degree of freedom of attentional choice. Thus, the effects of attentional choice (two-picture viewing) versus no-choice (one picture viewing) conditions on nicotine's ability to reduce negative affect will be assessed by presenting blocks with a series of 64 single or dual pictures on a computer. Mood will be assessed before and after each picture series block. The frequency of negative pictures in these series will be manipulated (either 16 [low frequency] or 48 [high frequency]). In the no-choice task, single pictures will be presented centrally on the computer screen. In the two-choice task, dual picture images will be presented simultaneously in the left and right visual field. Picture series blocks (64 single or dual pictures) will consist of the following 4.5 sec. sequence: the word "blink", a fixation cross, and a picture (or dual picture). In the two-choice condition, subjects will be instructed to allocate as much or little of their gaze time to a given picture, but to always be gazing at one of two pictures. In the no-choice condition, subjects will be required to maintain a 3 sec. gaze at each picture. Neutral or positive pictures will be interspersed in both the two-choice and no-choice tasks. Eye-gaze patterns during the two-choice task and no-choice task will be obtained with an infrared, computerized tracking system. In the two-choice task, maximal dysphoriareducing effects of nicotine are predicted to occur during blocks with a high frequency of negative pictures. Nicotine is predicted to reduce gaze directed toward negative pictures and to enhance attention to positive pictures. In the no-choice task, nicotine is expected to have maximal dysphoria-reducing effects when a low frequency of negative pictures is combined with intervening positive pictures. Potential moderating influences of gender, smoker-nonsmoker status, and individual differences in trait anxiety, depression, and anhedonia will be assessed with regression analyses. This work will use new experimental procedures and technologies, including the precise assessment to individual differences in continuously monitored eye-gaze patterns with an infrared,
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computerized tracking system. The new knowledge derived from these studies will be useful in developing empirical model-based treatment strategies aimed at increasing smoking abstinence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NICOTINE-INDUCED DOPAMINE CHANGES IN ADDICTED SMOKERS Principal Investigator & Institution: Mintun, Mark A.; Professor; Radiology; Washington University Lindell and Skinker Blvd St. Louis, MO 63130 Timing: Fiscal Year 2002; Project Start 10-MAY-2002; Project End 30-APR-2004 Summary: (provided by applicant) Nicotine dependence occurs in approximately 50 percent of daily smokers but the biology of the predisposition to nicotine dependence is unknown. Dopamine has been repeatedly found to play a central role in the reinforcing actions of numerous addicting drugs and may thus be an important determinant of addiction. Systemic administration of nicotine results in increased extracellular dopamine levels within the mesolimbic dopamine system that parallel those seen in cocaine and amphetamine administration. Furthermore, in animals the magnitude of the nicotine-induced changes in dopaminergic neurotransmission correlates with the rate of development of addiction behavior. This R21 project will test the use of positron emission tomography (PET) to measure the amount of dopamine released in the ventral striatum/nucleus accumbens after a nicotine challenge in cigarette smokers that are dependent on nicotine. Sensitivity to nicotine-induced dopamine release will be optimized by the use of 3D PET acquisition, higher raclopride dose (0.2 mCi / kg) and selective regions-of-interest for the mesolimbic system (predominantly the nucleus accumbens) drawn on high-resolution magnetic resonance images. We propose to study 30 daily smokers that demonstrate nicotine dependence (greater than 4 on the Fagerstom scale) using Li IC]raclopride PET and high resolution MRI. Each subject will undergo raclopride PET before and during a pharmacologic challenge. Ten subjects will receive placebo, ten subjects will receive 25 ug/kg i.v. and ten subjects will receive 50 ug/kg i.v. We will examine the hypotheses that systemic nicotine administration releases dopamine in the nucleus accumbens and that the amount of dopamine released is dependent on the plasma levels of nicotine achieved during the challenge. If completed, this R21 will demonstrate the utility of evaluating the mesolimbic dopamine release during nicotine exposure in smokers. We plan to use this information to design a subsequent project to investigate the biological differences between smokers who are not addicted and those smokers who are addicted. Ultimately, this information may lead to a better understanding of biological predispositions to nicotine dependence and potential treatment approaches for smoking cessation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NICOTINE'S EFFECTS ON OTHER DRUGS OF ABUSE Principal Investigator & Institution: Kouri, Elena M.; Assistant Professor; Mc Lean Hospital (Belmont, Ma) Belmont, MA 02478 Timing: Fiscal Year 2001; Project Start 15-SEP-1999; Project End 31-AUG-2003 Summary: This application Nicotine's Effects on Other Drugs of Abuse, investigates conditions under which nicotine may alter the reinforcing, subjective and physiologic effects of the two most widely used psychoactive drugs in the United States, marihuana and ethanol. Even though these substances are commonly used together, the medical consequences, pharmacokinetic profiles and reinforcing effects of these drug
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combinations are not well understood. The proposed studies will systematically assess whether nicotine pretreatment via a transdermal patch alters the pharmacodynamics and pharmacokinetics of acute marihuana and ethanol and will evaluate whether these interactions are dose- dependent. Study 1 will investigate these interactions in nonsmokers in order to characterize the nature of the pharmacodynamic interactions without the possible confounds introduced by variables associated with smoking. Studies 2-5 will use moderate tobacco smokers as subjects in an attempt to replicate conditions similar to those experienced by individuals who are treating their nicotine dependence with the patch and may continue to smoke marihuana or drink alcohol. These studies will also investigate whether nicotine alters ethanol's or marihuana's reinforcing effects by using a laboratory-based drug self-administration paradigm. In addition, because there is a paucity of research studies using women as subjects, and sex-related differences have been shown in the absorption, bioavailability, distribution and metabolism of various drugs of abuse, both male and female occasional drug users will be used in the studies to identify gender differences in the effects of these drug interactions. Finally, the influence of hormonal fluctuations associated with the menstrual cycle on the observed drug interactions will be investigated by studying women at different times of their menstrual cycle. The findings from the proposed studies will provide important information on the pharmacodynamic interactions and the reinforcing effects of these drug combinations. These findings will have direct public health implications because, since the nicotine transdermal patch is now over-thecounter, many individuals may be using it without medical supervision and at the same time using or abusing alcohol and other drugs. If nicotine increases the positive effects and decreases the negative effects of ethanol and marihuana, individuals using a nicotine transdermal patch may find these substances more reinforcing and may be more likely to increase their use, putting them at higher risk for developing dependence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NICOTINIC INVOLVEMENT & CONSUMPTION OF ALCOHOL IN HUMANS Principal Investigator & Institution: De Wit, Harriet; Associate Professor; Psychiatry; University of Chicago 5801 S Ellis Ave Chicago, IL 60637 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): We propose to investigate the involvement of nicotinic acetylcholine receptors (NAChR) in i) the consumption of alcohol, and ii) the subjective responses to alcohol in human social drinkers. Prior research has indicated an unequivocal relationship between nicotine and alcohol consumption with the use of one increasing the likelihood that the other will be consumed as well. Experimental studies in animals have repeatedly shown that alcohol consumption increases when a nicotine pretreatment is administered and recently a corresponding effect has been found in human social drinkers. It has been hypothesized that nicotine may alter the subjective responses to alcohol and that the stimulant-like effects and euphorigenic properties of alcohol may be mediated through action at NAChRs. The proposed studies will examine this relationship between the stimulant-like effects and consumption of alcohol and nicotinic acetylcholine function through two different approaches: nicotine administration and receptor blockade. Mecamylamine, a non-competitive, nicotinic receptor antagonist that readily passes the blood-brain barrier, will be administered in two studies to assess the effect of NAChR blockade on the subjective effects of alcohol and its consumption. We will investigate the efficacy of mecamylamine in attenuating the stimulant-like and euphorigenic properties of alcohol as well as its voluntary
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consumption. The third study proposed will administer nicotine through transdermal patches and assess its impact on the effects and consumption of alcohol. The proposed studies can be a significant and important first step in elucidating the interaction between two of the most commonly used drugs in this country. In addition to providing informative data on possible mechanisms mediating the reinforcing effects of alcohol, these studies can also serve as a first step to determining the efficacy of nicotinic antagonists as a treatment for alcohol abuse or dependence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NICOTINIC MECHANISMS IN SENSORY NEOCORTEX Principal Investigator & Institution: Connors, Barry W.; Professor; Neuroscience; Brown University Providence, RI 02912 Timing: Fiscal Year 2001; Project Start 05-MAY-1999; Project End 31-MAR-2003 Summary: (Adapted From The Applicant's Abstract): Nicotine is the world's most widely used addictive substance. Nicotine abuse, in the form of smoking, causes many chronic diseases and almost 20% of the deaths in developed countries. The mechanisms of nicotine's addictiveness are well studied. However nicotine has behavioral effects distinct from its physically addictive qualities, and these contribute to its popularity. Nicotine is said to elevate mood and arousal, reduce pain, and improve attention, working memory, and the rapid processing of sensory information. The mechanisms for these effects of nicotine are very poorly understood. Nicotine receptor in the brain have recently been implicated in a familial form of epilepsy and other neurological and psychiatric disorders, and drugs with nicotinic activity may have potential in the treatment of Alzheimer's and Parkinson's disease. The goal of this proposal is to study the cellular mechanisms of nicotine's effects on the forebrain, in particular the sensory neocortex. Neocortex and its connections comprise 80% of human brain volume, and it is essential for normal sensation, movement, memory and cognition. Nicotine's direct action on neocortex probably plays a major role in the drug's diverse effects on behavior. Nicotine binds to neuronal nicotinic acetylcholine receptors : in neocortex neuronal nicotinic acetylcholine receptors are abundant on the input (I.e. Thalamocortical) synapses to the cortex, and on some inhibitory and pyramidal neurons. The aims of this investigation are to test the hypothesis that nicotine, and the activation of specific neuronal nicotinic acetylcholine receptors, alters the strength and dynamics of input synapsis to the neocortex, modulates synaptic inhibition and inhibitory neurons, and thus systematically changes the way the neocortex transforms sensory information from the thalamus. Experiments will be performed in vitro and in vivo in the somatosensory system of rats. A formal computational model will be used to understand how nicotine's effects on neurons and synapses lead to complex but predictable alterations of the neocortical network, and thus alter sensation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NICOTINIC MODULATION OF THE MESOACCUMBENS DA SYSTEM Principal Investigator & Institution: Mcgehee, Daniel S.; Anesthesia and Critical Care; University of Chicago 5801 S Ellis Ave Chicago, IL 60637 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 30-NOV-2007 Summary: (provided by applicant): Nicotinic acetylcholine receptors (nAChRs) can modify synaptic transmission in many brain regions. Our recent studies show that nAChRs contribute to midbrain dopamine (DA) neuron excitability through modulation
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of both inhibitory GABAergic and excitatory glutamatergic inputs. The nAChR enhancement of glutamate inputs can contribute to LTP induction at this synapse. Interestingly, the nicotinic modulation of GABA transmission exhibits a transient enhancement, followed by a depression of activity. Apparently, desensitization of the nAChRs on GABA neurons inhibits endogenous cholinergic input to these cells, thus leading to a 'disinhibition' of the DA neurons. These studies were carried out in neonatal rats, primarily for technical reasons. Experiments in this proposal will extend these tests to tissue slices from adult rats that have undergone behavioral and pharmacological testing. The activity that an animal displays in a novel environment can predict nicotine self-administration in rats. The advantage of this screen is that animals predisposed to nicotine self-administration can be identified without nicotine exposure, which is known to alter sensitivity. Our preliminary results indicate differences in nAChR expression between high and low responders to novelty. We will extend these observations to test the differences in cellular and synaptic effects of nAChR activation associated with the predisposition to nicotine self-administration. The activity response to novelty has also been correlated with differences in stress hormone levels between individuals, leading to the suggestion that stress hormones contribute to the predisposition to drug-taking. Preliminary data indicate that stress hormones inhibit nAChRs through a direct interaction. We will test the hypothesis that this interaction upregulates the expression of nAChRs within the reward area, strengthens the cellular response to nicotine and thus, enhances the motivating effects of the drug. Nicotine exposure also enhances the acquisition of self-administration behavior, presumably through upregulation of nAChR expression. We will test nAChR effects on DA neuron excitability from animals that have been pre-exposed to nicotine by passive injection and self-administration testing. These studies of nAChR function within the brain reward center will provide important insights into the cellular basis of addiction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NICOTINIC TRANSPORTERS
RECEPTOR
REGULATION
OF
DOPAMINE
Principal Investigator & Institution: Middleton, Lisa S.; Behavioral Science; University of Kentucky 109 Kinkead Hall Lexington, KY 40506 Timing: Fiscal Year 2002; Project Start 01-JUL-2002 Summary: (Provided by Applicant): Tobacco smoking is the number one health problem accounting for more illness and death than any other single factor in the U.S. Nicotine, the major alkaloid in tobacco, has been shown to release dopamine (DA) from its presynaptic terminals, which is shown to be critical for its reinforcing effect leading to its abuse liability. Emphasis in the literature has been placed on the effect of nicotine on DA release, whereas the role of the dopamine transporter (DAT) has not been fully elucidated. Our preliminary data from our in vivo voltammetric studies demonstrate that following acute nicotine administration, DA clearance is increased in a dose-related manner in rat striatum and medial prefrontal cortex; however, the pattern of the doseresponse curves is different in these two brain regions. The research proposed in this application is designed to test the hypothesis that nicotine regulates DAT function through an interaction with nicotinic receptor sites. The proposed specific aims are to determine the effect of repeated peripheral NIC administration on DAT function in striatum and cortex to assess differential brain region specific nicotine-induced regulation of DA using in vivo voltammetry, determine if an increase in DAT efficiency is responsible for the nicotine-induced increase in DAT function using [3H]DA uptake and [3H]GBR12935 binding assays, determine if increased trafficking of DAT from
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internal sites to the presynaptic terminal membrane using the biotinylation assay accounts for the increase in DA clearance in response to nicotine administration, and if this response is mediated by nicotinic receptors. Results from these experiments will provide a better understanding of the role of DAT in nicotine addiction and begin to assess the mechanism whereby nicotine alters DAT function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NICOTINIC SUBUNITS AND NICOTINE'S CARDIOVASCULAR EFFECTS Principal Investigator & Institution: De Biasi, Mariella G.; Baylor College of Medicine 1 Baylor Plaza Houston, TX 77030 Timing: Fiscal Year 2001 Summary: Nicotine is the main addictive component of tobacco, and its behavioral and pharmacological effects are initiated by binding to neuronal nicotine acetylcholine receptors (nAChRs). Nicotine delivered by cigarette increasing the heart rate and blood pressure. The onset and duration of nicotine's peripheral effects vary. For instance, during habitual smoking, nicotine tolerance to the blood pressure effects develops faster than to the heart rate effects. Evidence suggests that the changing levels of nAChR desensitization are mechanistically linked to the development of tolerance, and desensitization and pharmacology are in turn linked to the subunit composition of the nAChRs. Although there are many in vitro studies that associated the functional properties of the receptors to their subunit composition, there are no in vivo studies that examine the systems level relationships between particular nAChR subunits and nicotine's effects. The guiding hypothesis of this proposal is that the subunit composition of nAChRs dictates the complex cardiovascular effects of nicotine, including the development of tolerance. To test our hypothesis, we will use in vivo and in vitro techniques to study mutant mice lacking nAChR subunits that are known to be expressed in the homeostasis, we will monitor blood pressure and the heart rate via radio-telemetry under basal conditions and in response to nicotine administrations. Radio-telemetry measures physiological signals and transmits them to distant receivers, thereby minimizing experimental artifacts arising from stress. The in vivo experiments will be accompanied by in vitro studies on cardiac contractility in response to nicotine and to adrenergic and cholinergic agonists. Receptor binding and in situ hybridization experiments will be conducted in collaboration with the Morphology Core to determine possible compensatory mechanisms as well as nAChR subunit up- regulation after chronic exposure to nicotine. Patch-clamp experiments in collaboration with Dr. Dani will provide information on the biophysical profile of nAChR currents in autonomic ganglia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: COGNITION
NICOTINIC-ANTIPSYCHOTIC
DRUG
INTERACTIONS
AND
Principal Investigator & Institution: Levin, Edward D.; Associate Professor; Psychiatry; Duke University Durham, NC 27706 Timing: Fiscal Year 2002; Project Start 12-DEC-2001; Project End 30-NOV-2006 Summary: Nicotine is self-administered via cigarette smoking by the great majority of patients with schizophrenia. Nicotine has direct effects on cognitive function and interacts with antipsychotic drugs to substantially influence their actions on cognitive function. The cognitive effects of nicotine may present a novel opportunity for
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improving the treatment of cognitive dysfunction associated with schizophrenia and cognitive dysfunction induced by antipsychotic drugs. Classical neuroleptics such as haloperidol and "atypical" antipsychotics such a clozapine and risperidone have substantially different mechanisms of action and likely interact with nicotine in quite different ways. The proposed project will determine the functional mechanisms by which nicotinic systems interact with antipsychotic drugs to affect cognitive function. Both classical and atypical antipsychotic drugs have been found to impair memory function. Haloperidol-induced working memory deficits have been found in our earlier studies of schizophrenic patients and laboratory rats to be reversed by acute doses of nicotine. Recently, we have found that the working memory impairment caused in rats by clozapine administration can be reversed by nicotine. These effects will be used as a forum in which to determine the critical neural mechanisms by which nicotine interacts with antipsychotic drugs in the control of memory function. We hypothesize that nicotinic receptor systems in the hippocampus are a key mechanism by which nicotine alleviates schizophrenia associated attentional impairment and antipsychotic druginduced memory impairment. Nicotinic innervation of the hippocampus has been found in our previous studies to be critical for nicotine effects on memory. Importantly, we have also shown that hippocampal DA innervation is also important for memory function. The proposed project will specify the mechanisms underlying nicotinic interactions with antipsychotic effects on memory function, including involvement of nicotinic receptor subtypes and their anatomic loci in hippocampus important for memory function. Dose response local infusion studies with selective nicotinic antagonist subtypes will be used to determine the relationship of nicotinic systems for memory performance in the benchmark radial-arm maze task as well as an operant attention task. These basic studies will help elucidate important therapeutic issues concerning the impact of nicotinic co- treatment with classic and atypical antipsychotic drugs to improve memory and attentional function. These studies will provide information concerning neural systems likely to underlie nicotinic actions we have seen on a systemic level and facilitate the development of new drug therapies for cognitive dysfunction in schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NORNICOTINE ADMINISTRATION
ENANTIOMERS
AND
NICOTINE
SELF
Principal Investigator & Institution: Bardo, Michael T.; Professor; Yaupon Therapeutics, Inc. 259 Radnor Chester Rd, Ste 210 Radnor, PA 19087 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2004 Summary: (provided by applicant): Nicotine is known to have an important role in tobacco dependence. However, in addition to nicotine, smokers are exposed to nornicotine both in the form of a tobacco alkaloid and as a metabolite that results from biotransformation of nicotine. Using an animal model of tobacco smoking in humans, we have found that nornicotine is self-administered in rats and that nornicotine pretreatment is effective in reducing nicotine self-administration. In addition, repeated administration of S(-)-nornicotine, but not R(+)-nornicotine, increases locomotor activity. In the current project, our overall hypothesis is that S(-)-nornicotine will be more potent than R(+)-nornicotine in selectively decreasing nicotine self-administration across repeated injections. The specific aims will determine if the nornicotine enantiomers differ in their ability to (1) dose dependently decrease nicotine selfadministration, (2) dose-dependently decrease sucrose-reinforced responding, and (3) decrease nicotine self-administration or sucrose-reinforced responding across repeated
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injections. Rats will be trained to self-administer nicotine to a stable rate and then will be pretreated with varying doses of either S(-)- or R(+)-nornicotine. To determine the specificity of the decrease in nicotine self- administration, separate groups of rats will be trained to respond for sucrose reinforcement and will be pretreated with varying doses of either S(-)- or R(+)-nornicotine. In another experiment, rats will be pretreated repeatedly with either S(-)- or R(+)-nornicotine and tested for nicotine selfadministration or sucrose-reinforced responding, thus assessing if effect of each nornicotine enantiomer is long-lasting or transient. The long-range goal of this preclinical work is to develop a novel medication for smoking cessation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NOVEL GENES INVOLVED IN DRUG RESPONSE Principal Investigator & Institution: Nichols, Ruthann; Associate Professor; Biological Chemistry; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, MI 481091274 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-JUL-2003 Summary: (provided by the applicant) Nicotine is the most addictive drug abused worldwide. On average over 430,000 Americans die each year from nicotine-related illnesses. A long-term goal of our research is to identify novel genes involved in mediating the effects of nicotine on human health to identify new target sites to develop medications to help people stop smoking. The largest portion of nicotine-related deaths is the result of cardiovascular failure due to high blood pressure and increased heart rate. Short-term administration of nicotine typically raises human heart rate by l0-25 bpm. The role of the central nervous system in mediating the effect of nicotine is not well understood. Although nicotine is known to act through catecholamines, blood pressure and heart rate rise before catecholamine levels, increase. Thus, molecules other than catecholamines, in part, mediate the effects of nicotine on cardiovascular parameters. Drosophila melanogaster is an established model organism for human drug addiction and cardiovascular research. We have developed an in vivo assay and determined that nicotine increases adult D. melanogaster heart rate. Our hypothesis is that P element disruption of a gene whose product mediates the effect of nicotine on the cardiovascular system will have an altered heart rate in response to this drug. To identify gene products involved in transducing the effect of nicotine on heart rate, we will (aim #1) analyze P element D. melanogastar insertion mutants. To verify the role of a gene product in mediating the effect of nicotine, we will (aim #2) generate a revertant of the mutant. A revertant in which the P element no longer resides in a gene will display a wild type phenotype when exposed to nicotine. To confirm the role of the candidate gene product, we will (aim #3) locate the P element insertion site to identify the altered gene. We will search for mammalian orthologs of the D. melanogaster gene products identified in our P element screen. Our future work will apply physiological and molecular genetic techniques in mouse to delineate the role of these novel molecules in transducing the effect of nicotine in mammals. Ultimately, our research will determine the role of these gene products in mediating the effect of nicotine in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: OPIATE AND NICOTINE DEPENDENCE--MEDICATIONS AND THERAPY Principal Investigator & Institution: Sullivan, Maria A.; Psychiatry; Columbia University Health Sciences New York, NY 10032
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Timing: Fiscal Year 2001; Project Start 01-SEP-1999; Project End 30-JUN-2004 Summary: Heroin and nicotine dependence are two addictions for which new combined pharmacotherapy/behavioral therapy interventions are possible. The goal of this mentored clinical scientist award is to promote the developing research skills of Maria A. Sullivan, M.D., Ph.D., by providing two areas of clinical research for testing novel combined medication/therapy strategies for opiate and nicotine dependence. Dr. Sullivan, a Board-Certified Psychiatrist, has completed a successful research fellowship in the Division on Substance Use at Columbia University/New York State Psychiatric Institute (NYSPI). As a fellow, Dr. Sullivan has begun studying patterns of smoking among schizophrenic patients and carried out a pilot intervention using bupropion/behavioral therapy to treat nicotine dependence among patients with chronic psychosis. This year Dr. Sullivan has joined the staff in the Division as an Assistant Professor of Clinical Psychiatry. She is currently serving as the Co-Director for the NIDA funded grant, "Opiate Dependence: Combined Naltrexone/Behavior Therapy." In the next several years, Dr. Sullivan plans to carry out clinical treatment trials to explore novel combined pharmacotherapy/psychotherapy approaches to opiate and nicotine dependence. Her proposed research plan will enable her to develop skills in two specific areas of addiction psychiatry: (1)conducting double-blind pharmacotherapeutic trials of agents which target specific mood symptoms in opiate or nicotine dependence or withdrawal; and (2)developing manualized psychotherapies tailored to promote abstinence and relapse prevention for individuals abusing certain classes of drugs. In this way, Dr. Sullivan will be well prepared to achieve her long-term research career goal of developing treatment approaches for comorbid substance use/psychiatric disorders. Under the sponsorship and guidance of Dr. Herbert Kleber, together with the faculty and resources available at Columbia University, Dr. Sullivan's training plan combines formal course work with clinical research experience at several sites of the New York State Psychiatric Institute. She will be working closely with several preceptors to receive training in the following areas: design and methods of clinical treatment studies; controlled medication trials; developing and implementing manual-guided relapse prevention therapies for opiate and nicotine dependence in selected populations; and biostatistics and epidemiology. Her specific research plan includes double-blind placebo-controlled trials of bupropion for nicotine dependence and nefazodone with open-label naltrexone for opiate dependence. For both treatment studies, manual-guided relapse prevention therapies will be developed and implemented. Dr. Sullivan's planned research will provide her with unique training and will afford her the opportunity to develop a clinical research career focused on developing new combined medication/therapy approaches to the treatment of substance abuse disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ORAL NICOTINE CONSUMPTION IN PERIADOLESCENT MICE Principal Investigator & Institution: Klein, Laura; Biobehavioral Health; Pennsylvania State University-Univ Park 201 Old Main University Park, PA 16802 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2003 Summary: (provided by the applicant) Nearly 90 percent of all smokers begin smoking during adolescence and about 3,000 adolescents start smoking every day in the United States. The likelihood of quitting smoking in adulthood is decreased dramatically when smoking initiation begins during adolescence. In fact, adolescents who start smoking today will smoke for as long as 20-30 years, on average, which also means that they are more likely to experience the adverse health consequences of smoking than are those
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individuals who start to smoke later in life. Despite these staggering statistics that suggest a developmental vulnerability to nicotine, little is known about the progression from adolescent experimentation with cigarettes into smoking addiction. Adolescent exposure to nicotine through cigarette smoking also appears to mark the first stage of additional addictive drug involvement in vulnerable individuals. One hypothesis consistent with these epidemiologic data is that the direct pharmacological actions of nicotine in adolescence may influence the vulnerability to consume addictive drugs, including nicotine, in adulthood. To the extent that animal models predict selfadministration of addictive substances in adults, they also could be used to understand why adolescent humans begin to smoke, and how smoking might increase the propensity to consume addictive drugs in some individuals. Unfortunately, behavioral animal models of adolescent drug self-administration are rare, particularly with respect to nicotine, the primary addictive ingredient in cigarettes. Therefore, the present proposal will examine the preference for nicotine in periadolescent mice given access to differences doses of nicotine. In addition, nicotine preference will be tested in adult mice following an opportunity to consume nicotine in the adolescent developmental period. Results from this work will set the stage for future research to characterize behavioral (drug self-administration) and biological (molecular, genetic, neuroendocrine) alterations that occur following adolescent exposure to nicotine and to aid in future development of therapies for smoking - the single most preventable cause of death in the United States. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ORAL NICOTINE REPLACEMENT FOR SMOKING CESSATION Principal Investigator & Institution: Westman, Eric C.; Medicine; Duke University Durham, NC 27706 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JUL-2006 Summary: (provided by applicant): This R21 application addresses the leading preventable cause of premature death in the United States, cigarette smoking. The most widely used treatment to help smokers quit is nicotine replacement therapy, but its success rates are only about 20% at six months. Based on a model of the smoking behavior involving nicotine, sensory, and habit effects, oral nicotine delivery in flavored beverages has been studied in two pilot projects to build on the concept of nicotine replacement therapy. This study continues the development of oral nicotine further by adding a placebo control group in a smoking cessation trial. The study is a two-group, parallel-design, placebo-controlled, randomized clinical trial. One-hundred healthy adult volunteers motivated to quit smoking will be randomized to receive either nicotine solution (active condition) or Iobeline solution (control condition). Subjects will be instructed to add the solution to the beverages of their choice every hour as needed for smoking urges for 6 weeks. All subjects will receive a self-help cessation manual, and brief individual counseling. Community volunteers will be recruited from the local metropolitan area by newspaper advertisements. Inclusion criteria are: 1) age from 18-65 years 2) smoking at least 10 cigarettes per day 3) desire to quit smoking 4) willingness to set a "quit date" within 14 days of enrollment. Major exclusion criteria are: 1) any ongoing medical problem requiring monitoring 2) prescription medication 3) pregnancy or breastfeeding. Baseline data collection includes smoking history, nicotine dependence questionnaire, smoking withdrawal and motivation questionnaires. Subjects will return on the quit date, every week for 6 weeks during treatment, then every month for 6 months. At each return visit subjects will complete an exhaled carbon monoxide test, and questionnaires regarding smoking withdrawal and solution
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tolerability. The primary outcome is continuous smoking abstinence 6 months after the quit date. Other outcomes include continuous smoking abstinence at 1 and 3 months, smoking withdrawal symptoms, side effects of treatment, treatment compliance, and sensory effects of treatment solutions. This study tests the preliminary efficacy of a promising novel nicotine replacement therapy compared to placebo. If efficacious, further research into its safety, efficacy, and mechanisms will be in order. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PASSIVE IMMUNOTHERAPY FOR NICOTINE ABUSE Principal Investigator & Institution: Carrera, M Rocio.; Scripps Research Institute 10550 N Torrey Pines Rd La Jolla, CA 920371000 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2005 Summary: (provided by applicant): Cigarette smoking prevails as the largest preventable risk factor for mortality in developed countries. Smokers procure their habit in order to maintain nicotine levels in the brain, where it exerts its powerfully addictive effects. Nicotine-replacement therapy, the most widely used treatment for nicotine dependence, has only been modestly successful. Immunopharmacotherapy offers an alternate venue, whereby the passage of nicotine into the brain is blocked by peripherally circulating anti-nicotine antibodies, thereby circumventing central pharmacological interventions. In laboratory animals, nicotine induces two main behavioral correlates: a distinct, biphasic pattern of psychomotor induction, and the selfadministration of the drug due to its positive reinforcing properties. In order to explore the efficacy of passive immunization against the psychoactive and rewarding effects of nicotine in the rat, a comprehensive psychopharmacological assessment using various animal behavioral paradigms is proposed. First, the efficacy of the anti-nicotine monoclonal antibody NIC9D9 in blocking the psychomotor effects of nicotine will be tested using an animal model of locomotor activity. Second, a nicotine selfadministration dose-response assay will be employed to study the effects of NIC9D9 on the reinforcing properties of nicotine. Lastly, in the effort to address the grave problem of relapse among cigarette smokers, an extensive study using a well-established animal model of nicotine self-administration reinstatement will be conducted. Together, the proposed studies will provide important insight into the potential benefits of immunopharmacotherapy against nicotine addiction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PATHOPHYSIOLOGY OF NICOTINE IN CEREBRAL BLOOD VESSELS Principal Investigator & Institution: Simard, J Marc.; Professor; Neurosurgery; University of Maryland Balt Prof School Baltimore, MD 21201 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-MAR-2005 Summary: (Verbatim from the Applicant's Abstract) The alkaloid, nicotine, the primary component of tobacco that drives its habitual use, is a major health hazard with proven deleterious effects on the cerebral circulation, Epidemiological evidence indicates that smoking elevates risk of stroke by promoting development of atherosclerosis, formation of multiple cerebral aneurysms, and vasospasm following subarachnoid hemorrhage. Ca dysregulation in vascular smooth muscle may play an important role in nicotineinduced cerebral vasculopathy by predisposing to elevated intracellular CA, leading to Ca-mediated cell injury and cell death. We have made novel observations on effects of nicotine in patch clamp studies of cerebrovascular smooth muscle cells: 1) we found
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that prolonged exposure (3 hr) of vessels to nicotine causes a significant increase in Ca channel availability in smooth muscle cells subsequently isolated from the vessels; 2) we found that prolonged exposure of vessels to nicotine abrogates normal downregulation of Ca channel availability by nitric oxide (NO), but does not affect normal upregulation of Ca activated K (BK) channel activity by NO. These and other findings have led us to hypothesize that nicotine may exert its deleterious effects by blocking a protein phosphatase that may be important in regulating Ca channel availability, and that this mechanism may not involve a classical nicotinic receptor. The purpose of this grant is to 1) elucidate mechanism(s) for the effects of nicotine on Ca channel availability and on NO-signalling that we observed in smooth muscle cells following prolonged and chronic exposure of intact vessels to nicotine, and 20 to elucidate normal regulation of Ca and BK channels in cerebrovascular smooth muscle by tyrosine kinases and phosphatases, the balance between which may be altered by nicotine. We will use patch clamp techniques, supplemented with antibody/immunofluorescence techniques, Western blots and electron microscopy, to study Ca and BK channel regulation in freshly isolated smooth muscle cells from rats after prolonged (> 3 hr) and chronic (6 months) exposure to nicotine and other pharmacological agents. The proposed studies will constitute the first physiological demonstration of effects of nicotine on cerebrovascular smooth muscle CA and BK channels, and will be the first to address cellular mechanism of nicotine-induced CA channel dysregulation in smooth muscle cells from cerebral arterioles. The importance of this work lies in 1) elucidating a new physiological mechanism related to NO -induced downregulation of Ca channels in cerebrovascular smooth muscle cells, and 2) elucidating a new pathophysiological mechanism related to nicotine-induced changes in cerebral blood vessels that may predispose to stroke. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NICOTINE
PAVLOVIAN
CONDITIONING
PROCESSES
INVOLVING
Principal Investigator & Institution: Bevins, Rick A.; Associate Professor; Psychology; University of Nebraska Lincoln 14Th and R Sts Lincoln, NE 68588 Timing: Fiscal Year 2001; Project Start 01-JUN-1999; Project End 31-OCT-2003 Summary: Conditioning (learning) processes involving stimulus-nicotine associations are believed to be a major factor contributing to the continued abuse of tobacco products. The present proposal will use an animal model to elucidate the processes involved in the acquisition and expression of a conditioned association between environmental stimuli and nicotine. In this preparation, a distinct environment that has been repeatedly paired with nicotine comes to elicit an enhancement of activity relative to control conditions. This enhanced activity is taken as evidence for an association between the environment and the locomotor stimulant effects of nicotine. Specific Aim 1 will assess competing accounts of the enhanced locomotor activity --- excitatory Pavlovian conditioning vs. inhibitory conditioning or novelty-induced activity. The goal of Specific Aim 2 will be to manipulate procedural variables found in other Pavlovian conditioning preparations to alter learning (e.g., number of conditioning trials, temporal relation between environment and nicotine). In doing so, more optimal conditioning procedures will be identified. Specific Aim 3 will investigate whether nicotine preexposure attenuates subsequent nicotine locomotor conditioning as predicted by theories based on research with traditional Pavlovian conditioning paradigms or whether nicotine pre-exposure facilitates the conditioned locomotor effects as characterized by a smaller set of literature in the drug conditioning field. This aim will
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also determine how the conditioned and unconditioned locomotor effects of nicotine vary as a function of different pre-exposure protocols (e.g., context, number, interdose interval, continuous vs. intermittent delivery). Elucidating the behavioral processes underlying acquisition and expression of Pavlovian drug conditioning will have important implications for prevention and intervention strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PEDIATRIC PHARMACOLOGY RESEARCH UNIT Principal Investigator & Institution: Kearns, Gregory L.; Professor of Pediatrics; Children's Mercy Hosp (Kansas City, Mo) 2401 Gillham Rd Kansas City, MO 64108 Timing: Fiscal Year 2001; Project Start 01-JAN-1994; Project End 31-DEC-2003 Summary: The propose epidemiologic family study will systematically examine the vulnerability to nicotine dependence due to the combined transmission of genes and family/cultural environmental factors (e.g., familial liability). Four areas are addressed in the proposed study: 1) the familial liability for nicotine dependence associated with different phenotypes or characteristics of nicotine dependence (e.g. also meeting DSMIV criteria); 2) the degree of shared familial liability dependence and non- familial environmental factors in the etiology of nicotine dependence; 4) familial liability, nonfamilial factors, and individual factors that may be partially under genetic control (such as nicotine metabolism) that contribute to estimated differences in nicotine dependence between African Americans and Caucasians, both to spotlight factors that contribute to nicotine dependence in a group at high risk of cancer mortality (African Americans) and to identify protective factors by comparing racial groups with substantially different cigarette smoking profiles. This epidemiologic case-control family study is designed to examine the familial transmission of nicotine dependence among adults 25 to 44 years of age and their families. This range will be used because the period of risk for daily smoking is largely concluded by age 25 and adults between these ages are still likely to have living parents. Cases will be nicotine dependent by a threshold score of 4 or more on the Fagerstrom Test of Nicotine Dependence (FTND). Controls will be smoking exposed (having smoked at least 100 cigarettes) but never nicotine dependent (FTND=0). For cases on sibling and both parents will be sought. For controls one sibling will be sought. Direct interviews will be conducted with the case and control family members. The information gathered will include their cigarette smoking, psychiatric disorders, and other substance use, as well as demographic and medical history information. All of the interviewed family members will provide family history of cigarette smoking, substance use and psychiatric disorders. Additionally, cases and controls will be asked about the cigarette smoking, alcohol use and behavior problems of their offspring. This study provides a population-based context for genetic and metabolism studies in the Collaborative Study on the Genetics of Nicotine Dependence. Ascertainment, interviewing, and data management will be integrated across studies. Additionally, as part of the unique opportunity presented by the scientific integration of Projects 1, 2, and 3 we will incorporate genetic, metabolic and epidemiologic measures of a broad array for factors in the development of risk factor models for nicotine dependence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PERFUSION FMRI OF CUE-INDUCED NICOTINE CRAVING Principal Investigator & Institution: Franklin, Teresa R.; Psychiatry; University of Pennsylvania 3451 Walnut Street Philadelphia, PA 19104
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Timing: Fiscal Year 2003; Project Start 10-SEP-2003; Project End 30-APR-2006 Summary: (provided by applicant): This five year training program is the path that Teresa R. Franklin, Ph.D., a Post-doctoral Fellow at the TRC, University of Pennsylvania, will travel to become an independent investigator with expertise in brain imaging and substance abuse research. The foundation underlying this proposal is her behavioral neuroscience background in which she studied conditioned responses to drug-related environmental cues. The proposal outlines the training and research experience necessary for her to develop and launch a fully independent career using a novel imaging technique, perfusion fMRI, to characterize the CNS structures underlying cueinduced nicotine craving. An extensive training program is required to prepare Dr. Franklin to fill the role of an independent investigator, as several research areas new to her are involved. Dr. Franklin will participate in ongoing structured didactics in human ethics, biostatistics and fMRI. She will attend and present at international- nationaluniversity- and center-wide seminars, forums and meetings; and will receive hands-on mentored training in collection and analysis of perfusion fMRI data. The candidate will be supported by a Mentoring team and Advisory board with expertise in areas critical to her proposal; clinical substance abuse research (Childress, O'Brien), neurobiology of nicotine dependence (Lerman), cue-induced drug craving (Childress, O'Brien), biostatistics, fMRI imaging and analysis techniques (Listerud) and perfusion fMRI (Listerud). Dr. Franklin will focus on the phenomenon of cue-induced nicotine craving during her training using arterial spin labeled (ASL) perfusion fMRI. This technique will be used to determine regional brain activation (Study 1, Aim 1) and possible sex differences (Study 1, Aim 2) in response to smoking cues. ASL perfusion fMRI is ideally suited for imaging low frequency changes observed in behavioral states, such as craving, that recruit over time. ASL perfusion fMRI will diminish susceptibility artifact in brain regions that are important in drug dependence but difficult to elucidate with BOLD fMRI (e.g., ventromedial prefrontal cortex). In Study 2, Dr. Franklin will assess the impact of a promising anticraving medication, the GABA B agonist, baclofen, on subjective and brain responses to nicotine cues. Tobacco use is a monumental health concern as it is the number one cause of preventable death in our nation. Despite current interventions, smoking relapse rates remain high: 80-95% at one year post cessation. Thus, research into its neurological underpinnings is critical in guiding the development of behavioral and pharmacological therapies to battle nicotine addiction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PERIPHERAL VASCULAR EFFECTS OF TRANSDERMAL NICOTINE IN NON SMOKERS Principal Investigator & Institution: Mcphail, Ian R.; Mayo Clinic Rochester 200 1St St Sw Rochester, MN 55905 Timing: Fiscal Year 2001 Summary: Cigarette smoking is a major risk factor for the development of cardiovascular disease. Although nicotine is the addictive component of cigarette smoke, the vascular effects of nicotine in the absence of smoking are incompletely understood. The purpose of this study is to examine the vascular effects of transdermal nicotine in non-smokers. Specifically, brachial artery reactivity and nitric oxide levels will be compared in non-smokers in the absence and presence of transdermal nicotine. This study will be a double-blind, randomized, placebo-controlled trial. 44 healthy subjects will be enrolled in the parent protocol "Nicotine Patch Treatment as an Anorectic (IRB 951-97). Brachial reactivity and nitroc oxide levels will be tested at baseline (without nicotine), 6 hours after the initial patch application (acute effect) and
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after 8 weeks of patch treatment (chronic effect). If alterations in brachial artery reactivity are observed in response to nicotine, parallel changes in nitric oxide levels may be the mediator of this response. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PHARMACOGENETIC INVESTIGATION OF NALTREXONE Principal Investigator & Institution: Lerman, Caryn E.; Professor of Psychology in Psychiatry; Psychiatry; University of Pennsylvania 3451 Walnut Street Philadelphia, PA 19104 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 30-JUN-2008 Summary: (provided by applicant): Several converging lines of evidence support the role of the endogenous opioid system in the reinforcing effects of nicotine; however, the efficacy of opioid antagonists (e.g., naltrexone, NTX) for the treatment of tobacco dependence remains unresolved. The results of clinical studies of NTX for tobacco dependence are inconsistent, which may reflect individual differences in drug response. Rather than concluding that NTX is an ineffective treatment for tobacco dependence, research is needed to identify those smokers for whom NTX will have the strongest beneficial effects on smoking behavior. Therefore, the specific goal of the proposed research is to test whether genetic variation in the functional mu-opioid receptor gene predicts the effects of NTX on cigarette smoking and nicotine reinforcement. Based on preclinical animal and human research, we hypothesize that smokers with the OPRM1 Asp40 variant will be more likely to respond to NTX compared to placebo (PLA), as reflected in reduced cigarette smoking and lower levels of nicotine reinforcement. This hypothesis will be tested using two within-subject behavioral pharmacology paradigms in which NTX 50mg and PLA will be administered to smokers who have been genotyped for OPRM1. The first experiment will examine the effects of NTX on the risk of relapse following an initial smoking lapse, using the validated experimental model of relapse designed by Stitzer and colleagues. Following 3 days of NTX (or PLA) and verified smoking abstinence, 70 smokers (35 from each genotype group) will be exposed to a "programmed" smoking lapse, and then monitored for three days in their natural environments. Following a 5-day wash-out period, the sequence will be repeated with NTX or PLA (order of medications counterbalanced). The primary outcomes are cigarette smoking and nicotine levels following the lapse episode. While such adlibitum smoking experiments are more naturalistic, these designs can't disentangle the effects of a medication on the reinforcing value of nicotine from effects on the reinforcing value of smoking (including conditioned reinforcers). Therefore, the second experiment will examine the effects of NTX (vs. PLA) on the reinforcing value of nicotine, using a validated cigarette choice paradigm, developed by Perkins and colleagues. In this experiment 80 smokers genotyped for OPRM1 (40 from each genotype group) will receive acute pre-treatment with NTX 50mg or PLA following overnight abstinence, and before they participate in the cigarette choice procedure. The primary outcome will be the number of puffs taken from a 0.6 mg nicotine cigarette versus a 0.05 (denicotinized) cigarette during a 3-hour period. Following a washout period, the sequence will be repeated (with NTX or PLA). The long-term objective of this research is to discover and develop new pharmacogenetic treatment models that can be readily translated to the clinical setting to individualize pharmacotherapy and maximize effectiveness. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PHARMACOKINETICS OF NICOTINE IN TWINS Principal Investigator & Institution: Swan, Gary E.; Director; Sri International 333 Ravenswood Ave Menlo Park, CA 94025 Timing: Fiscal Year 2001; Project Start 05-MAR-1998; Project End 28-FEB-2003 Summary: (Applicant's Abstract) Despite the best efforts to date, 46 million people still smoke, and 430,000 people die from tobacco-related illness annually; the estimated smoking-related cost to the economy is $72 billion annually. The question remains why some people smoke and not others. The proposed research plan seeks to explore, for the first time, the genetic influences on the disposition and kinetics of nicotine, stable characteristics of individuals that may be central to understanding of nicotine addiction and its effective treatment. We will recruit 250 twin pairs over 4 years (100 monozygotic [MZ] and 100 dizygotic [DZ] never smoking pairs, 25 MZ and 25 DZ pairs in which one twin is a never smoker and the other twin is a current or former smoker). The inclusion of never smoking twins will allow us to test initial biological differences and similarities in nicotine metabolism and kinetics in a group with no previous exposure to nicotine. The inclusion of MZ and DZ twin pairs discordant for ever smoking will facilitate the estimation of the genetic correlation between nicotine metabolism and nicotine dependence. Reported zygosity and smoking status will be confirmed by biochemical methods. After completion of a brief questionnaire designed to screen for exclusionary health conditions and to assess potentially confounding variables, subjects will be seen as twin pairs for an 8-hour in-hospital nicotine infusion test. During the 8 hours after the 30-minute infusion, blood and urine samples will be taken at regular intervals for assay of nicotine and metabolites. At each of the subsequent four mornings, project staff will drive to the homes of the subjects to collect blood and 24-hr urine samples. After the assay is completed, the data will be subjected to both univariate and multivariate genetic analyses to determine genetic and environmental influences on each pharmacokinetic parameter individually and in combination with other biologically meaningful indices of nicotine metabolism. Implications of this project are seen for: (1) estimation of the impact of genetic influences on nicotine metabolism and (2) further refinement of the metabolic phenotype associated most strongly with the genetic predisposition to nicotine addiction. Through later molecular analysis of the stored blood to be collected as part of this project, we may be able to identify gene variants that underlie the amount and function of various enzymes responsible for metabolism of nicotine. Ultimately, this knowledge may lead to more informed and more finely targeted treatment of individuals who are either susceptible to nicotine addiction or are already addicted to this substance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PILOT STUDY--CNS VIRAL INJURY AND VULNERABILITY TO NICOTINE ABUSE Principal Investigator & Institution: Solbrig, Marylou V.; University of California Irvine Campus Dr Irvine, CA 92697 Timing: Fiscal Year 2001 Summary: The magnitude of the problem of nicotine abuse to our society and our health care delivery system underscores the importance of research efforts to understand the biology of nicotine use and abuse. There is increasing experimental evidence to support a role for repeated stimulation of the - mesolimbic dopamine neurons in the development and maintenance of nicotine dependence. In fact, the effects of nicotine on brain catecholamine systems are thought to be among nicotine's
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most important CNS actions. Using a small animal model of viral-induced mesocorticolimbic DA - hyperactivity based on Boma Disease Virus-BDV (an animal model of schizophrenia), the proposed experiment will explore the relation between a non-lesion animal model of DA hyperactivity, caused by persistent CNS viral infection, and drug-seeking behavior. The animal model will be developed then tested for the dependence-inducing effects of nicotine, as measured by the somatic signs of nicotine withdrawal, and the affective (emotional) effects of nicotine withdrawal, as measured by place aversion (Specific Aim 1). Knowledge of how an encephalitic viral infection producing dopaminergic disturbances influences nicotine dependence could provide new insights into mechanisms of nicotine dependence, and aid in understanding the comorbidity of nicotine abuse and neuropsychiatric conditions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PILOT STUDY--MRS STUDY OF NOCOTINE WITHDRAWAL AND NEGATIVE AFFECT Principal Investigator & Institution: Epperson, Cynthia N.; Assistant Professor; Yale University 47 College Street, Suite 203 New Haven, CT 065208047 Timing: Fiscal Year 2001 Summary: The incidence of cigarette smoking addiction in individuals with major depression is reported to be approximately 50%. That nicotine can be "protective" against depressive symptoms in this patient population and that nicotine may even have antidepressant effects in non-smoking depressed patients is suggestive of a complex interplay between nicotine and neurochemicals, responsible for regulation of mood. Nicotine has been shown to have effects on glutamate in the rodent cortex and gamma- aminobutryic acid (GABA)ergic and glutamatergic systems in rodent hippocampus. Using proton magnetic resonance spectroscopy (1H-MRS) our group has found a reduction in occipital cortex GABA levels in smoking and non-smoking patients with major depression compared to healthy smoking and non-smoking controls. In addition, depressed smokers had a 25% reduction in cortical GABA levels compared to depressed non-smokers. The overarching goal of this project is to further knowledge of the pathophysiology of nicotine addiction and nicotine's effects on negative effect by conducting 1H-MRS to measure cortical GABA, glutamate and glutamine pre and post 40 hours smoking abstinence in three groups; 1) depressed smokers, 2) non-depressed smokers with a history of major depression, and 3) healthy smoking controls. The pilot study outlined in this proposal will provide the first in vivo characterization of the impact of nicotine withdrawal on cortical amino acid neurotransmitters in humans. Findings from this investigation will serve to direct us in the development of a full-scale investigation in which we would include alcohol use as an additional focus, conduct 1HMRS scans over a longer course of abstinence and match our subjects on a greater number of variables. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PILOT STUDY--NICOTINE ROLE IN REGULATION OF NACHR IN DROSOPHILA Principal Investigator & Institution: O'dowd, Diane K.; Associate Professor; University of California Irvine Campus Dr Irvine, CA 92697 Timing: Fiscal Year 2001 Summary: Recent studies suggest that modifications in the number and function of nAChRs, by exposure to nicotine, plays an important role in the process of addiction.
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However, the molecular mechanisms important in regulating these receptors in the mammalian CNS remain poorly understood. In this grant we propose to address this question in Drosophila, a simple, genetically accessible model system. We have recently demonstrated that nAChRs, blocked by both curare and alpha-BTX, mediate the primary form of fast excitatory transmission between cultured Drosophila neurons, providing a unique opportunity to explore the genetic and biochemical signals important in regulation of these receptors and transmission at central cholinergic synapses. Our initial experiments will focus on characterization of the properties of the whole cell currents induced by acute exposure of cultured wildtype neurons to various concentration of nicotine. The second specific aim will examine the role of nicotine in regulation of the-functional nAChRs. Potential changes in the biophysical properties of these receptors will be assessed by monitoring the electrophysiological properties of nicotine-induced, ACh-induced, and cholinergic excitatory postsynaptic currents (EPSCs), following chronic exposure to nicotine. To determine if there are changes in the numbers of receptors, 125l-alphaBTX binding will be monitored before and after exposure to nicotine. In the third aim we will examine the effects of short duration, repetitive exposure to nicotine, mimicking the exposure that occurs during smoking, on nAChR expression. Finally, we will examine the properties of nicotine induced currents and regulation of nAChRs in neurons from dunce, a learning and memory mutant with defects in CAMP-signaling. Differences in the electrophysiological and pharmacological properties of the nAChRs and cholinergic synaptic currents between dunce and wildtype neurons will be important in determining if nicotine activates the same CAMP-signaling cascade that is important in reinforced learning paradigms in flies. The results of our studies will provide important insights into the molecular mechanisms underlying nicotine induced regulation of nAChRs. These data will also contribute to the general understanding of the molecular mechanisms important in regulating transmission at excitatory synapses, likely to be highly conserved between vertebrates and invertebrates, and therefore should aid in the design of drugs and/or therapies aimed at modulating plasticity in synaptic pathways contributing to addiction in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PILOT STUDY--PROLACTIN RELEASING PEPTIDE AND NICOTINE Principal Investigator & Institution: Civelli, Olivier; Profesor; University of California Irvine Campus Dr Irvine, CA 92697 Timing: Fiscal Year 2001 Summary: Prolactin (PRL) is secreted not only to support reproductive functions and lactation but also to maintain homeostatic functions under stress. Consequently, PRL release is known to be regulated not only by endogenous releasing factors but also by exogenous chemical substances with anti-stress activities. Prominent among these is nicotine which causes the release of PRL by acting CNS sites, in particular the nucleus tractus solitarius (NTS). The mechanism by which nicotine modulates PRL release is poorly understood. Recently, a 3 I-amino acid peptide, named the Prolactin Releasing Peptide (PrRP), was isolated which potently induced prolactin release from primary pituitary cells. Our preliminary data indicate that the PrRP mRNA is present in the NTS while its receptor is found in the hypothalamus. These data suggest that PrRP may be another important mediator of nicotine-induced PRL release. Upon nicotine stimulation, PrRP may be released from the NTS to act either on the hypothalamus and induce the release of other prolactin-releasing peptides or by being secreted in the potal blood and acting directly on the pituitary. We therefore propose to test the hypothesis of
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a direct link between PrRP and nicotine, by showing that PrRP is present in the nicotine sensitive (~ positive) NTS neurons and that nicotine induces PrRP release in the cerebrospinal fluid. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PILOT STUDY--SELEGILINE FOR SMOKING CESSATION Principal Investigator & Institution: George, Tony P.; Assistant Professor of Psychiatry; Yale University 47 College Street, Suite 203 New Haven, CT 065208047 Timing: Fiscal Year 2001 Summary: We are proposing a placebo-controlled pilot study of selegiline versus placebo for nicotine dependent smokers (N=30) with depressive symptoms. There is evidence that catecholamines have an important role in the rewarding and withdrawal effects of tobacco smoking, and monoamine oxidase inhibitors (MAOIs) which augment catecholamine (i.e. dopamine, norepinephrine) function may be helpful in attenuating nicotine craving and withdrawal symptoms in nicotine dependent smokers. Thus, the selective MAO-B inhibitor selegiline may be helpful as a pharmacologic adjunct for smoking cessation. The proposed study would be a 6 week trial in nicotine-dependent smokers which will compare selegiline (10 mg daily; n=15) versus placebo (n=15) treatments on smoking cessation outcomes. Subjects would be inducted onto 10 mg/day of selegiline (5 mg po bid) or matching placebo (twice daily) over a two week period prior to the "quit date" at the beginning of Week 1. All subjects would receive brief weekly sessions of smoking cessation counseling consistent with AHCPR smoking cessation guidelines. The primary outcome measures include 1 week post-quit (Week 2) and endpoint (Week 6) smoking abstinence rates, and continuous smoking abstinence during the last four weeks of the trial. Secondary outcomes measures include treatment retention, depressive symptoms, nicotine withdrawal symptoms, weight change, plasma cotinine levels, expired breath carbon monoxide (CO) levels and urinary catecholamine excretion. Data analyses to compare groups will focus of an intention-totreat sample and will utilize Chi square 2x2 contingency tables for smoking abstinence rates, repeated measures analysis of variance (ANOVA) models for continuous outcome measures (i.e. depression and nicotine withdrawal ratings, CC, plasma cotinine and urinary catecholamines) and Kaplan-Meir survival analysis for treatment retention. Results from this pilot study would be used to calculate an effect size for planning a larger controlled trial if results from this pilot study appear promising. We predict that selegiline will be superior to placebo for smoking cessation in nicotine dependent smokers on both primary and secondary outcome measures. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PILOT STUDY--TRANSGENIC APPROACH TO PREDILECTION OF NICOTINE ABUSE Principal Investigator & Institution: Zhou, Qun-Yong; Assistant Professor; University of California Irvine Campus Dr Irvine, CA 92697 Timing: Fiscal Year 2001 Summary: The mesolimbic dopamine system mediates the reinforcing effects of nicotine and other drugs of abuse. Thus the genes affecting the functionality of the mesolimbic dopamine system can be contributing factors to predisposition to nicotine abuse. These genes include dopamine receptors, signaling molecules of cAMP pathway such as adenylate cyclase, and others. Evidence put forth by a number of investigators suggests that the difference in the different biochemical profile of cAMP pathway in the
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mesolimbic dopamine system may result in differential predilection to abused drugs. The precise relation of up-regulated cAMP signaling pathway~y and nicotine predilection, however, remains vague. The present study seeks to bridge this gap by investigating the consequence of up-regulated cAMP pathway in transgenic mice, caused by a subtle substitution mutation in the dopamine D2 receptor, on nicotine responsiveness. Particularly, these studies seek to produce a strain of transgenic mice that express the mutant D2 receptor and to investigate whether the mutant D2 receptor will result in up-regulation of cAMP pathway in transgenic mice and therefore increased vulnerability to nicotine abusing. The availability of transgenic mice expressing the mutant D2 receptor will help establish the causal effect relationship of an up- regulated cAMP pathway and predilection to nicotine abuse. The proposed studies will also lead to an understanding of whether a subtle change in structure of dopamine D2 receptor, one of mediators for the basic neurobiological function of mesolimbic dopamine system, may affect predisposition to nicotine abuse. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PILOT--HPA REACTIVITY Principal Investigator & Institution: Stroud, Laura; Miriam Hospital Providence, RI 02906 Timing: Fiscal Year 2001 Summary: (Applicant's Description) To target vulnerable youths for intervention and prevention efforts, it is critical to identify biobehavioral factors that distinguish adolescents at increased risk for progressing to nicotine dependence. One factor shown to be associated with nicotine dependence in humans is dysregulation of the hypothalamic pituitary- adrenocortical (I-IPA) stress axis. However, it is unclear whether this dysregulation results from chronic nicotine use, or whether it precedes use and might distinguish those at increased risk for progressing to dependence. In laboratory animals, dysregulation of the adrenocortical stress hormones has been shown to both precede psychostimulant use and to distinguish animals with a greater propensity for psychostimulant self-administration. Animals who demonstrated greater reactivity to stress showed increased propensity for self-administration of various psychostimulants. Yet, the relationship between stress reactivity and increased risk for drug dependence has never been tested in humans or with nicotine. The proposed pilot study will investigate differences in adrenocortical reactivity between adolescents at greater and lesser risk for progression to nicotine dependence. Specifically, as prenatal nicotine exposure has been associated with increased risk for progression to nicotine dependence, we will examine the relationship between HPA stress reactivity and maternal smoking during pregnancy. Three groups of twenty same-sex adolescent sibling pairs will be recruited for the study including a) sibling pairs concordant for maternal smoking during pregnancy (MS-H-), h) pairs discordant only for maternal smoking during pregnancy (MS+-), and e) matched control pairs with no maternal history (MS--)of smoking. Groups will be compared on adrenocortical reactivity to a series of laboratory stressors. We hypothesize that the MS++ sibling pairs will show greater adrenocortical stress reactivity than the MS+- sibling pairs, who will show greater reactivity than the M-- pairs. Moreover, MS+ siblings from the MS+- pairs will show similar reactivity to the MS++ pairs and greater reactivity than the MS-siblings from the MS+- pairs, who will show reactivity similar to the MS-- pairs. Results will represent a first step toward characterizing a biobehavioral marker for nicotine dependence and may elucidate mechanisms underlying the effects of maternal smoking during pregnancy. Results may also lead to longitudinal marker studies with
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implications for genetic mechanisms as well as targeted intervention and prevention efforts. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PILOT--PRENATAL DOPAMINERGIC SYSTEM
NICOTINE
EXPOSURE
AND
THE
Principal Investigator & Institution: Garcia-Davila, Martha I.; Georgetown University Washington, DC 20057 Timing: Fiscal Year 2001 Summary: The mesolimbic system has been implicated in the addictive properties of most drugs of abuse and dependence including cocaine, heroin, amphetamines and nicotine from tobacco. Nicotine affects the dopaminergic system in multiple ways including increasing both the firing rate and bursting activity of dopaminergic cells and by enhancing synthesis, metabolism and release of dopamine. In these studies we propose to examine, using an animal model, the acute and chronic effects of nicotine of dopaminergic function (dopamine release and dopamine uptake) at various developmental ages. The relationship The relationship between the nicotine-induced change in nicotine acetylcholine receptor (nAChR) numbers following chronic prenatal nicotine and the number of dopamine transports will also be assessed. Finally, the identify of the nAChR involved in the dopaminergic regulation will be determined by labeling the receptors with [125I]epibatidine, a high affinity radioligand for a variety of nAChRs, and immunoprecipitation of the receptors with subunit-specific antibodies. To determine the identify of these nAChRs involved in regulating dopaminergic function may lead us to a better understanding of nicotine's effects in brain and in addictive properties during various developmental stages. This knowledge will also help in the development of specific therapeutics, as well as in assessing the validity of using nicotine as a therapeutic agent in developmental disorders or during pregnancy as an aid to quit smoking. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PILOT--PROBING FOR ACTIVE SITE RESIDUES OF NICOTINE METABOLIZING HUMAN FMO3 Principal Investigator & Institution: Atta-Asafo-Adjei, Emmanuel; Vanderbilt University 3319 West End Ave. Nashville, TN 372036917 Timing: Fiscal Year 2001; Project Start 16-JUL-2001; Project End 30-APR-2006 Summary: The mammalian flavin-containing monooxygenases (FMOs) are enzymes distributed in the liver, lung and kidney of mammals. They catalyze the oxidation of a wide variety of foreign compounds or xenobiotics, including pesticides and narcotic drugs like nicotine. To date, five distinct members of this protein family, designated FMO 1, 2, 3, 4, and 5, have been identified in mammals including humans. Human FMO3, the dominant isoform of FMO in human liver, has been observed to exclusively convert nicotine to an all trans carcinogenic nicotine-N-1'- oxide. By contrast, the cytochrome P450s oxidize (S)-nicotine to a mixture of cis- and trans-N'-oxides. Interestingly, in smokers, the trans- N-1'-oxide ste has been proposed as a stereoselective functional biomarker for FMO3 in humans. Interestingly, the specific role of the FMOs relative to that of the cytochrome P450s in microsomal or in vivo oxidative metabolism of xenobiotics in mammals is not well defined, due to lack of non-substrate inhibitors specific and selective for the FMO isoforms. As a result, the relative contribution of FMOs in xenobiotic metabolism, is often deduced by inhibiting the reactions catalyzed
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primarily by the cytP450s. The lack of inhibitors selective for the FMOs may be due in part, to the paucity of information about the amino acid determinants of the substratebinding sites of FMOs. The specific goal of this project therefore, is to identify the amino acid determinants of the substrate binding sites of especially, the long cancer implicated human FMO3 by: (1) using photoaffinity labeling studies followed by time-of- flight mass spectrometry (MALDI-TOF) to identify any covalently labeled residues. The probe to be used is photoactivatable N, N- dimethyl-4-azidoaniline, an azido-derivatized substrate analog of N, N- dimethylaniline, an FMO marker substrate. Oligonucleotidemediated site-saturation mutagenesis will subsequently be used to ascertain whether residues, identified by the photolabeling/MALDI-TOF studies are critical for substrate binding. We hope the identification of residues crucial for substrate binding and catalysis will help us to search for and/or design FMO isoform selective inhibitors Availability of such inhibitors, should help researchers to do more definitive studies to determine the specific role of human FMO3 in the bioactivation of xenobiotics like nicotine to carcinogenic metabolism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PRENATAL, CHILD, AND FAMILY RISKS Principal Investigator & Institution: Buka, Stephen L.; Associate Professor; Miriam Hospital Providence, RI 02906 Timing: Fiscal Year 2001 Summary: (Applicant's Description) The proposed project addresses: a) the effect of in utero exposure (IUE) to nicotine and other prenatal and childhood conditions on the risk of nicotine dependence in adulthood; and b) the familial aggregation of nicotine dependence and related phenotypes. Building on current research in this area, findings from the proposed study will advance the field of nicotine research in at least two important ways. Firstly, the proposed study will use prenatal and early childhood measures collected prospectively in a large community sample, enabling statistically powerful analyses of multiple and alternative early risks for adult nicotine dependence. Secondly, through a hybrid design we examine hypotheses and anticipate future studies of gene:environment interactions in the etiology of adult nicotine dependence. We focus primarily on a specific environmental risk, in utero exposure (IUE) to nicotine both based on the strength of the existing human and animal study data and for parsimony of effort. We have developed a sampling and measurement strategy intended both to distinguish the role of IUE from other salient characteristics of pregnant women who smoke and from known sequelae of IUE that may explain or mediate any observed link between IUE and later nicotine dependence. In so doing, we are able to simultaneously investigate the predictive utility of a range of hypothesized prenatal, childhood and familial risks for adult nicotine dependence. We propose to accomplish these aims through a, multidisciplinary, multi- method longitudinal investigation. The proposed project integrates: 1) a natural history study of the smoking trajectories and associated behaviors through mid-life of subjects whose mother did and did not smoke during pregnancy; 2) a family study of sibling pairs, discordant for maternal smoking during pregnancy; 3) a sibling study of current or ex-regular smokers to investigate the familial aggregation of nicotine dependence and related phenotypes; and 4) a baseline assessment of current smokers targeted for a randomized smoking cessation trial. The resulting 40-year prospective study will: 1) determine whether nicotine dependence is elevated among adult offspring exposed in utero to nicotine; 2) investigate the mechanisms for this potential association; 3) identify prenatal, child and familial risks f adult nicotine dependence; and 4) examine patterns of familial aggregation to identify
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potential mechanisms for familial clustering and identify the components of nicotine dependence that may be familial. These data will provide an empirical basis for conducting future studies of susceptibility genes for nicotine dependence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PROBING FOR ACTIVE SITE RESIDUES OF HUMAN FMO3 Principal Investigator & Institution: Atta-Asafo-Adjei, Emmanual; Meharry Medical College 1005-D B Todd Blvd Nashville, TN 37208 Timing: Fiscal Year 2001; Project Start 03-AUG-2001; Project End 30-APR-2006 Summary: The mammalian flavin-containing monooxygenases (FMOs) are enzymes mainly distributed in the liver, lung and kidney of mammals. They catalyze the oxidation of a wide variety of foreign compounds or xenobiotics, including pesticides and narcotic drugs like nicotine. To date, five distinct members of this protein family, designated FMO 1, 2, 3, 4, and 5, have been identified in mammals including humans. Human FMO3, the dominant isoform of FMO in human liver, have been observed to exclusively convert nicotine to all trans carcinogenic nicotine- N-1'-oxide. By contrast, the cytochrome P450s oxidative (S)- nicotine to a mixture of cis- and trans-N'-oxides. Interestingly, the specific role of the FMOs relative to that of the cytochrome P450s in microsomal or in vivo oxidative metabolism of xenobiotics in mammals is not well defined, due to lack of non-substrate inhibitors specific and selective for the FMO isoforms. As a result, the relative contribution of FMOs in xenobiotic metabolism, is often deduced by inhibiting the reactions catalyzed primarily by the cyts P450s. The lack of inhibitors selective for the FMOs may be due in part, to the paucity of information about the amino acid determinants of the substrate-binding sties of FMOs. The specific goal of this project therefore, is to identify the amino acidic determinants of the substrate binding sites of especially, the lung cancer implicated human FMO3 by: (1) using photoaffinity labeling studies followed by time-of-flight mass spectroscopy (MALDITOF) to identify any covalently labeled residues. The probe to be used is photoactivatable N,N-dimethyl-4-azidoaniline, an azido-derivatized substrate analog of N, N-dimethylaniline, an FMO marker substrate. Oligonucleotide-mediated sitesaturation mutagenesis will subsequently be used to ascertain whether residues, identified by the photolabeling/MALDI-TOF studies are critical for substrate binding. We hope the identification of residues critical binding and catalysis will help us to search for and/or design FMO isoform selective inhibitors. Availability of such inhibitors, should help researchers to do more definitive studies to determine the specific role of human FMO3 in the bioactivation of xenobiotics like nicotine to carcinogenic metabolites. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PROGESTRONE AND THE EFFECTS OF NICOTINE Principal Investigator & Institution: Sofuoglu, Mehmet; Psychiatry; Yale University 47 College Street, Suite 203 New Haven, CT 065208047 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-MAY-2007 Summary: (provided by applicant): Although women represent close to half of the smokers in the U.S., how sex and phase of the menstrual cycle affect nicotine dependence is not well understood. Studies suggest that women, compared to men, may be less sensitive to the subjective and reinforcing effects of nicotine. The menstrual cycle phase may affect smoking behavior and the severity of tobacco withdrawal symptoms in female smokers. These sex and menstrual cycle effects could be due to fluctuations of
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female sex steroid-hormones, estradiol and progesterone, within the menstrual cycle. In a pilot study with overnight abstinent female smokers, we have observed that progesterone treatment attenuates the subjective effects of the first cigarette and craving for cigarettes. We conjecture that the attenuation of nicotine's reinforcing effects by progesterone may contribute to the observed sex and menstrual phase effects on nicotine dependence in humans. The goal of this proposal is to extend our preliminary findings by systematically examining the effects of progesterone on smoking behavior, tobacco withdrawal symptoms and subjective rewarding effects of smoking. This will be a double-blind, placebo-controlled study in which male and female smokers will be randomly assigned to one of the 3 treatment conditions: placebo, low (200 mg/day) or high dose (400 mg/day) of progesterone for four days. Subjects will abstain from smoking for the first 3 days of the treatment period, followed by an ad lib smoking session on day 4. We hypothesize that progesterone treatment, dose-dependently, will reduce smoking behavior, attenuate tobacco withdrawal symptoms, and subjective rewarding effects of smoking in both male and female smokers. By characterizing the progesterone effects on nicotine dependence, this study may provide a better understanding of the mechanisms which mediate the sex and menstrual cycle phase effects on nicotine dependence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REDUCING CHILDREN'S EXPOSURE TO TOBACCO SMOKE Principal Investigator & Institution: An, Larry; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, MN 554552070 Timing: Fiscal Year 2001 Summary: Tobacco smoke pollution is a major cause of disease and death for children in this country. While there has been some progress limiting tobacco smoking pollution (TSP) in public and work places, relatively little attention has focused on improving air quality in homes and private spaces where children receive their greatest exposure to TSP. As a result in the United States each year, children continue to suffer more than 5 million additional episodes of illness leading to nearly 4,000 preventable deaths due to the effects of tobacco smoke pollution (Aligne, 1997; US EPA, 1993; California EPA, 1997; DiFranza, 1996). This proposal represents a developing collaboration between the U.S. Environmental Protection Agency, a large regional health maintenance organization (Health Partners, Minnesota), and an international team of researchers in an innovative effort to change parental smoking behavior in order to reduce children's exposure to TSP. Parental, and especially maternal, smoking in the home is the major source of children's exposure to TSP. All smoking parents should be advised and assisted in quitting. For the majority of smoking parents initially unable or unwilling to quit, efforts should focus on helping them limit their children's exposure to TSP. Promising counseling interventions have been developed to help parents create reduced-smoke and smoke-free environments for their children. Unfortunately, parents' continued smoking commonly results in continued exposure for the child and parents may need additional assistance to create truly smoke-free environments. Since nicotine addiction is often a major force driving continued cigarette use, providing smoking parents an alternative non-polluting source of nicotine (i.e. nicotine gum) for use in the home may help reduce their dependence on cigarettes and their children's TSP exposure. Through a population-based environmental assessment survey of a large health plan's youngest members, we will identify families with infant children exposed to maternal smoking in the home (a marker for higher levels of overall TSP exposure). Smoking mothers will be recruited into a prospective 3 group randomized clinical trial to determine the ability of
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(1) individualized counseling and (2) individualized counseling plus access to nicotine gum as a substitute for cigarettes in the home to help mothers create smoke-free environments for their children. Specifically, we hypothesize that compared to usual care (advice to quit and written materials promoting a smoke-free environment for children): 1. Providing smoking mothers with individualized counseling focused on TSP reduction will reduce children's exposure to TSP. 2. Providing smoking mothers with individualized counseling focused on TSP reduction plus access to nicotine gum as a substitute for cigarettes in the home will further reduce children's exposure to TSP. 3. Engaging smoking mothers in interventions to reduce children's exposure to TSP will reduce maternal cigarette consumption and increase maternal smoking cessation. In addition, we will explore a secondary set of hypotheses on the relative economic costs and benefits of the study interventions. Specifically, we hypothesize that, if sufficiently effective, the study interventions: (a) will also be a cost-effective (in terms of cost per life year gained) when compared to widely prescribed medical treatments; and (b) will lead to reductions in medical, mortality and morbidity costs that fully or partially offset the costs of the intervention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF NEURONAL NICOTINIC RECEPTORS Principal Investigator & Institution: Wecker, Lynn; Professor and Chair; Pharmacology and Therapeutics; University of South Florida 4202 E Fowler Ave Tampa, FL 33620 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 30-JUN-2006 Summary: (provided by applicant): Nicotine is a potent central nervous system stimulant whose effects are mediated through interactions with neuronal nicotinic receptors, a family of receptors composed of a or a and 13 subunits. Receptors containing a4 and 132 subunits are the most abundant receptors in the brain, and exhibit high affinity for agonist. These receptors inactivate and exhibit an increased density following sustained exposure to nicotine, although the mechanisms mediating these effects are not clearly unders aboutod. Based on studies indicating that a4132 receptors either isolated from rat brain or expressed in Xeno pus oocytes are phosphorylated by protein kinases, that the surface expression and function of a4B2 receptors stably expressed in HEK 293 cells are modified by activators and inhibitors of protein kinases, and that nicotine enhances receptor phosphorylation, it is likely that these receptors may be regulated by phosphorylation/ dephosphorylation mechanisms, posttranslational processes that regulate other ligand-gated ion channels. The goal of these studies is to elucidate the role of phosphorylation/dephosphorylation mechanisms in mediating the effects of the chronic administration of nicotine or nicotinic agonists. This goal will be achieved by testing the hypothesis that a4 subunits of a4132 neuronal nicotinic receptors are phosphorylated/dephosphorylated by specific protein kinases/phosphatases and that alterations in the phosphorylation state of the a4 subunit following sustained exposure to nicotine or nicotinic agonists alters the function of the receptor. To test this hypothesis, cellular and molecular studies will be carried out using Xenopus oocytes expressing rat a4B2 receptors, SH-EPI cells stably expressing human a4B2 receptors, transiently transfected SH-EP-1 cells expressing mutant a4 subunits with wild-type 132 subunits, primary neuronal cultures, fusion proteins corresponding to the major cytoplasmic domain of the a4 subunit, and synthetic peptides corresponding to sequences within the cytoplasmic domain of the a4 subunit that contain putative phosphorytation sites. These studies will determine: I) whether changes in the phosphorylation state of the receptor affect its function; 2) which amino acids are phosphorylated/dephosphorylated and wnich enzymes are involved; 3) how nicotine
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and nicotinic agonists alter the phosphorylation/ dephosphorylation of the receptor; and 4) whether phosphorylationidephosphorylation alters receptor function. Results will provide knowledge on the regulation of a4132 receptors which is necessary for understanding both normal brain function and the long-term consequences of exposure to nicotine and nicotinic agonists, pharmacological agents that have been and continue to be abused, as well as used therapeutically. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE OF NICOTINE METABOLISM IN ADDICTION Principal Investigator & Institution: Murphy, Sharon; Washington University Lindell and Skinker Blvd St. Louis, MO 63130 Timing: Fiscal Year 2001; Project Start 28-SEP-2001; Project End 31-AUG-2006 Summary: A number of biological factors may influence an individual's smoking behavior. These include a smoker's sensitivity to and metabolism of nicotine. Specifically, we will determine if different parameters of nicotine metabolism are predictors of tobacco consumption and nicotine addiction. These parameters include: 1) P0450 2A6 phenotype 2) nicotine metabolism to continue; 3) nicotine metabolism by Nglucuronidation and N-oxidation. The major pathway of nicotine metabolism is conversion to cotinine, and there is strong in vitro data supporting a key role for P450 2AG phenotype 2) nicotine metabolism is cotinine; 3) nicotine metabolism by Nglucoronidation and N-oxidation. The major pathway of nicotinine metabolism is conversion to cotinine, and there is strong in vitro data supporting a key role for P450 2A6 as the catalyst of the first step in this pathway. P450 2A6 activity varies significantly between people. Therefore, P450 2A6 is an attractive candidate both as a key enzyme in nicotine addiction. These parameters include: 1) P450 2A6 phenotype 2) nicotine metabolism to cotinine; 3) nicotine metabolism by N-glucoronidation and oxidation. The major pathway of nicotine metabolism is conversion to cotinine, and there is strong in vitro data supporting a key role for P450 2A6 as the catalyst of the first step in this pathway. P450 2A6 activity varies significantly between people. Therefore, P450 2A6 is an attractive candidate both as a key enzyme in nicotine metabolism in smokers and as an important biological determinant of tobacco consumption and nicotine addiction. It is our hypothesis that an individual's ability to metabolize nicotine does influence tobacco consumption and thereby there sensitivity to related to nicotine addiction. Within a population of addicted smokers there is a wide range of cigarette consumption and nicotine addiction. It is our hypothesis that an individual's ability to metabolize nicotine does influence tobacco consumption and thereby there sensitivity to related to nicotine addiction. Within a population of addicted smokers there is a wide range of cigarette consumption. We hypothesize that some of this variation is due to differences in metabolism and that tobacco consumption influences nicotine addiction. In our Aims we will test this hypothesis, and the hypothesis that P450 2A6 is a key enzyme in nicotine metabolism but not the only enzyme responsible for the proposed relationship between nicotine addiction and metabolism. Our Specific Aims are to determine: 1) the correlation between the rate of nicotine clearance (following infusion) and P450 2A6 phenotype, 2) if a smoker's P450 phenotype predicts their urinary nicotine metabolite profile, 3) the relationship of either P450 2A6 phenotype or nicotine profile to tobacco consumption and nicotine addiction, and 4) whether an individual's nicotine metabolite profile and/or P4502A6 phenotype is a determinant of the familial distribution of tobacco consumption and nicotine addiction. Aim 4 will carry out a sibling pair analysis of nicotine metabolism tobacco consumption and nicotine addiction to investigate the
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degree to which metabolism contributes to the familiarity of tobacco consumption and nicotine addiction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE OF THE A4B2 NICOTINE RECEPTOR IN NEUROPATHOLOGY Principal Investigator & Institution: Carlson, Janice; Clinical Research Center; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, CA 90024 Timing: Fiscal Year 2002; Project Start 07-APR-2002 Summary: Nicotine produces a highly restricted pattern of degeneration with in the rat brain. As this is only a recent finding, this research is produced more questions than answers, especially concerning the long-term effects of this treatment. It appears that nicotine is expecting a large portion of its neurotoxicity, it has also seems to play a role in the neuroprotection against various neurotoxins and possibly neurological disorders such as Parkinson's Disease and Alzheimer's Disease. Therefore, this research proposal focuses on the various aspects of nicotine neurotoxicity as mediated by nicotine's actions on this receptor. Experiments will focus on determining the extent of the alpha4beta2's role in both neurotoxicity and the long-term impact of this treatment on this receptor population. Finally, experiments will focus on the potential neuroprotective role of the alpha4beta2 receptor against two neurotoxins used as animal models of disease, and the effect of these neurotoxins on the alpha4beta2 population. It is my hope that these experiments will shed light on how nicotine is both neurotoxic and neuroprotective, and how the alpha4beta2 receptor may be involved in these seemingly opposite effects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SAFETY OF A NICOTINE REDUCTION STRATEGY Principal Investigator & Institution: Benowitz, Neal L.; Professor of Medicine; Langley Porter Psychiatric Institute; University of California San Francisco 500 Parnassus Ave San Francisco, CA 94122 Timing: Fiscal Year 2001; Project Start 01-JUN-1999; Project End 31-MAR-2003 Summary: That nicotine addiction sustains tobacco use for most smokers is well established. Once a person is addicted to nicotine, quitting smoking is difficult, and more than 90 percent of smokers who try to quit each year fail. It follows that an important component of a policy to reduce tobacco use in the population is to prevent development of nicotine addiction in young people. Young people do not start to smoke because they are addicted, but once they begin to smoke become addicted, which sustains smoking into adulthood. It is difficult to prevent adolescents from experimenting with cigarettes; however, by reducing the content of nicotine in tobacco products, it may be possible to prevent the transition from experimental smoking to addiction. The Food and Drug Administration has gained jurisdiction to regulate nicotine, but FDA does not know yet how best to do it. One of the most widely discussed proposals is a gradual reduction of the nicotine content of all cigarettes to a level that does not sustain nicotine addiction. Such a cigarette could prevent adolescents from becoming addicted, and might also serve to wean adult smokers to a lower level of addiction and, therefore, facilitate quitting. Of concern with such a policy is whether compensatory oversmoking of cigarettes will be harmful to already addicted smokers. This proposal aims to examine the safety of reducing the nicotine content of cigarettes gradually. Volunteer smokers will smoke research cigarettes with progressively reduced nicotine contents over three or six months, with concomitant assessment of exposure to
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tobacco smoke nicotine, gas and tar, using the biomarkers of blood and urinary cotinine, urinary nicotine and metabolites, carboxyhemoglobin, urinary mutagenicity, urine solanesol, as well as measurement of cigarette puffing behavior. To examine the importance of the rate of nicotine reduction, measurements will be made in smokers in conditions where nicotine content is tapered over 12 weeks compared to over 24 weeks. The proposed research is needed to guide the FDA as how best to regulate nicotine in cigarettes and is an essential first step in examining the feasibility of a national nicotine regulation program. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SCALING THE REINFORCING VALUE OF CIGARETTE SMOKE Principal Investigator & Institution: Rose, Jed E.; Medical Research Professor; Psychiatry; Duke University Durham, NC 27706 Timing: Fiscal Year 2001; Project Start 30-SEP-1981; Project End 31-JAN-2004 Summary: The main goal of the proposed research is to determine how the pharmacologic actions of nicotine and the sensory/behavioral aspects of cigarette smoking contribute to tobacco dependence. In the proposed work, the pharmacologic effects of smoking will be delivered using intravenous (i.v.) nicotine infusions; conversely, the non-nicotine components of the smoking habit will be conveyed using de-nicotinized cigarettes. By dissociating and independently varying these two key components, we will gain a better understanding of the reinforcement processes maintaining smoking behavior. Laboratory studies will assess the determinants of nicotine self-administration and preference between nicotine and non-nicotine components of cigarette smoke. We will measure how preference for nicotine is affected by nicotine replacement in the form of nicotine skin patches. The ability of nicotine and non- nicotine smoke components to satiate smoking behavior will also be assessed. The relative roles of peripheral and central nervous system nicotinic receptors will be examined using different nicotinic antagonists. In addition to participating in the laboratory studies, subjects will be able to enroll in a smoking cessation program using nicotine skin patch therapy. Responses to i.v. nicotine and to the sensory/behavioral cues in the laboratory studies will be correlated with the clinical response to nicotine replacement treatment. The results will lead to a better understanding of the role of pharmacologic and sensory/behavioral cues in nicotine addiction and smoking cessation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SCHEDULED SMOKING WITH TRANSDERMAL NICOTINE Principal Investigator & Institution: Cinciripini, Paul M.; Professor; Behavioral Science; University of Texas Md Anderson Can Ctr Cancer Center Houston, TX 77030 Timing: Fiscal Year 2001; Project Start 01-APR-1998; Project End 31-MAR-2004 Summary: (Applicant's Abstract) Transdermal nicotine has been recently approved for OTC use and now provides millions of smokers with access to an effective form of nicotine replacement. Evidence from a variety of studies (i.e., Fiore, et. al., 1996), suggests that cessation efficacy may be enhanced by combining the patch with behavioral interventions aimed at improving the smoker's coping skills and urge resistance. Thus, there is a need to develop new treatments, which are compatible with the self-help focus of OTC patch treatment, and have the potential to produce sustainable changes in such behavior. Recent developments in behavioral and computer technology suggest that "scheduled smoking" (smoking at designated times prior to
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quitting), may be well suited for this purpose. Relative to traditional gradual or abrupt quitting, scheduled smoking results in higher rates of long-term abstinence, coping behavior, and self-efficacy, and lowered levels of negative affect. Moreover, use of small a programmable computer to administer the intervention, may improve patient acceptability and deliver schedules uniquely tailored to the individual's smoking pattern. A total 675 smokers from the Houston community will be randomly assigned to 3 groups: Scheduled Smoking (SS), Nicotine Patch (NP), and Scheduled Smoking plus Nicotine Patch (SSNP). Each participant will receive a self-help Tip Guide & Calendar. The guide contains basic cessation advice common to all groups, as well as instructions specific to the use of scheduled smoking, nicotine replacement, or their combination. During a one-week baseline, all participants will monitor their smoking using the "PalmPilot", Personal Digital Assistant (PDA). The PDA will automatically record the date and time of all cigarettes smoked. Over the next three weeks, NP participants will continue to monitor smoking, while Scheduled Smoking (SS) and Scheduled Smoking plus Nicotine Patch (SSNP) participants, are prompted to smoke at specific times of the day by the PDA. The program gradually increases the interval between prompted cigarettes, using an algorithm based on baseline smoking frequency and time awake. On the quit-date, both smokers in the NP and SSNP conditions will begin 6 weeks of transdermal nicotine replacement. The NP group will receive 3 weeks of nicotine replacement at 21mg/day; 2 weeks at 14mg/day, and one week at 7mg/day. The SSNP group will begin NRT at a dose commensurate with the degree of reduction achieved by scheduled smoking. Most smokers will start at 7mg/day. All participants will also receive regularly scheduled postcards, which highlight cessation tips selected from the guide. We hypothesize that smokers receiving the combined treatment (SSNP) will be abstinent more often, and show greater changes in coping and other behaviors, than smokers in either the SS or NP groups. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SENSITIVITY TO EMOTIONAL DISTRESS Principal Investigator & Institution: Zvolensky, Michael J.; Assistant Professor; Psychology; University of Vermont & St Agric College 340 Waterman Building Burlington, VT 05405 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 29-SEP-2004 Summary: (provided by applicant): The problem of relapse continues to plague public health efforts to reduce the prevalence of cigarette smoking. Recent evidence suggests that a large percentage of individuals attempting smoking cessation lapse to smoking within a matter of days, and that very few of these individuals are able to recover to achieve abstinence from smoking. Current models of relapse devote insufficient attention to this phenomenon of early lapse. Given the physiological and psychological disruption that occurs within hours of nicotine deprivation, nicotine withdrawal might be expected to play a strong role in early lapse and subsequent relapse, yet results of studies attempting to relate severity of nicotine withdrawal symptoms to short-term smoking cessation outcomes have been equivocal. Recent findings suggest the need for an expanded perspective recognizing the central role of negative affect in nicotine withdrawal. In this regard, we believe that the study of factors surrounding sensitivity to symptoms of nicotine withdrawal is a promising avenue of investigation. The overall aim of this B-Start application is to examine variables that index a latent sensitivity to the negative emotional distress that occurs in the context of a smoking cessation attempt, Specifically, the present proposal will examine the extent to which distress tolerance and anxiety sensitivity, variables theoretically linked to an underlying
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sensitivity to negative emotional distress, predict early lapse among regular smokers. It is hypothesized that anxiety sensitivity and tolerance for emotional distress on a laboratory stressor task will predict the duration of quit attempt even after controlling for baseline levels of negative emotionality and smoking characteristics. We expect that the results of this study will provide a more comprehensive understanding of variables that might serve as indicators of an inherent sensitivity to negative affect and thereby contribute to early relapse to smoking. Early relapsers represent a recalcitrant group of smokers who are at-risk for continued nicotine dependence and its associated morbidity and mortality. Findings from this investigation should result in improved methods of identifying smokers at-risk for early lapse, so that they may be targeted for nicotine dependence treatments that will meet their specific needs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SEX DIFFERENCES IN THE EFFECTS OF NICOTINE Principal Investigator & Institution: Eissenberg, Thomas Evan.; Assistant Professor; Virginia Commonwealth University Richmond, VA 232980568 Timing: Fiscal Year 2001; Project Start 30-SEP-1988; Project End 31-JUL-2006 Summary: Each year, cigarette smoking costs an estimated 418,000 American lives. Smoking cessation reduces this work, but is extremely difficult because smoking is maintained by factors such as nicotine withdrawal, tobacco's direct effects, and smoking-related stimuli that can control smoker's behavior. Current cessation methods address these factors. Nicotine replacement treatment suppresses withdrawal and/or blunts the effects of cigarettes. Behavioral treatments reduce the influence of smokingrelated stimuli. Nonetheless, about 70% of smokers who try to quit, fail. Improving smoking subgroups, such as men and women. Treatment studies demonstrate that quitting is more difficult for women. There is no definitive explanation for this sex difference, but it may involve a differential response to nicotine replacement treatment and/or smoking- related stimuli. For women, nicotine replacement may be less effective at suppressing withdrawal symptoms (Hypothesis 1) or at blunting the effects of cigarettes smoked during a quit attempt (Hypothesis 2). Women may also be more sensitive to smoking-related stimuli, such as the taste, sight, and smell of cigarette smoke (Hypothesis 3). These hypotheses can be examined efficiently in the clinical laboratory. Strengths of this setting include control over extraneous variables, repeated measure designs that yield nicotine dose effect curves, and validated tools for measuring puff topography, tobacco withdrawal, and the direct effects of nicotine and/or cigarettes. Three such studies are proposed. In each study, 45 men and 45 women non-treatment seeking smokers will participate in 4 double blind, randomly ordered, 6.5-hour sessions. Objectively verified cigarette abstinence will be required before each session. Studies 1 and 2 will compare, in men and women, the nicotine dose response functions for suppression for tobacco withdrawal and for blunting the effects of cigarettes. Study 3 will compare, in men and women, the effects of smoking-related stimuli (denicotinized cigarettes). Thus hypotheses 1, 2, and 3 will be addressed in separate studies in this 5-year project. The project will help to elucidate the mechanism underlying oft-reported sex differences in smoking cessation and may help tailor combined pharmacological and behavioral treatments that maximize the likelihood of cessation for men and women smokers. Given the overwhelming costs of cigarette smoking and the dramatic reduction in those costs when smokers quit smoking, improving the treatment options for all American smokers is essential. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SMOKING AND ATHEROSCLEROSIS: MECHANISMS AND MODULATION Principal Investigator & Institution: Burke, Anne; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, PA 19104 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 30-JUN-2006 Summary: Objectives: This research is to investigate a mechanism of smoking induced atherosclerosis and to assess the impact of smoking reduction strategies on arterial injury. Improving our understanding of smoking induced atherosclerosis will increase our armamentarium against this and non-smoking induced atherosclerosis. Specific aims: 1) To address the hypothesis that nicotine substitution or buproprion reduces smoking induced thromboxane (TX) formation and consequent endothelial dysfunction. 2) To address the hypothesis that nicotine substitution or buproprion reduces the smoking induced increment in isoprostane generation and inflammatory cytokines. 3) To address the hypothesis that smoking reduction may improve endothelial function even in the absence of smoking cessation. Relationship to health: Smoking is the leading cause of preventable death in America. Smoking costs the United States approximately $1 billion per annum. Reducing the harm of smoking will have a considerable impact on the health and health care costs of the United States. Research design: Healthy endothelium displays a vasodilatory response to vasoactive stimuli, which is blunted or absent in arterial disease. Flow mediated vasodilatation (FMD) can be measured noninvasively by ultrasound and correlates closely with subsequent development of atherosclerosis. Urinary isoprostane measured by gas chromatography / mass spectrometry (GC/MS) provide a specific and sensitive means to measure oxidative stress (OS) in vivo in humans. GC/MS also allows for accurate non-invasive quantification of TX and prostacyclin (PGI2) metabolites in humans. This research will be carried out in healthy age and gender matched human volunteers. Subjects will be studied for 6 months. It will quantify FMD in non- smokers, light and heavy smokers, before and after administration of vitamin C - an antioxidant, and aspirin - an inhibitor of TX and PGI2 synthesis. It will correlate FMD and eicosanoid production, before during and after smoking cessation on nicotine and non-nicotine smoking cessation medications. In addition, this research, in a separate experiment, will study the impact of nicotine and non nicotine assisted smoking reduction strategies on these parameters. Expected findings: We expect to find that smokers have impaired FMD and elevated OS, TX and PGI2 production. We expect that smoking reduction and cessation and the administration of antioxidants and aspirin will improve these parameters towards the levels of healthy volunteers and that the effects will be additive. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SMOKING CESSATION AMONG METHADONE MAINTAINED PATIENTS Principal Investigator & Institution: Stein, Michael D.; Professor of Medicine and Community Hea; Rhode Island Hospital (Providence, Ri) Providence, RI 02903 Timing: Fiscal Year 2001; Project Start 01-JUN-2001; Project End 31-MAY-2005 Summary: Opiate dependent persons who are successfully engaged in the treatment of their primary drug of addiction often continue to use other drugs such as nicotine. With the high prevalence of smoking in this population, treatment providers are recognizing that many of those they help recover are now dying of smoking-related illnesses, including cancer. Recent surveys indicate that persons enrolled in methadone maintenance treatment programs are interested in receiving smoking cessation
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treatment, particularly as treatment facilities go smoke-free through voluntary efforts or JCAHO mandates. The long-term aim of our proposal is to advance knowledge and produce interventions to help achieve optimal dissemination of stroking cessation strategies for those usually deprived of such programs with dual diagnosis of opioid dependence and nicotine dependence. Using a two-group design, we will enroll 408 methadone-maintained cigarette smokers from two methadone treatment programs in Rhode Island. The specific aims are: A.1. To test, in combination with the nicotine patch, the incremental efficacy of a maximal, tailored and sustained behavioral treatment over a minimal treatment in the setting of a methadone maintenance program. The defined population comprises low income, less educated smokers who will vary in their level of motivation to quit smoking. Patients will be randomly assigned to one of two treatments.(a) Nicotine patch prescription plus brief nurse advice and follow-up .(minimal treatment; and (b) Nicotine patch prescription, brief nurse advice and followup, with the addition of a tailored motivational intervention, a behavioral skills counseling session for smoking cessation, and continued telephone counseling (maximal treatment). We hypothesize that 6 month 7-day point prevalence quit rates will be 4% and 12% in each of the two treatment groups, respectively. A2. To test the effects of the treatments on intermediate variables including motivation to quit smoking, cognitive behavioral mediators of motivation and intention to quit (e.g. self-efficacy, pros and cons of smoking, perceived vulnerability to illness, and perceived ability to prevent illness by quitting smoking), frequency of patch use, and number of quit attempts. We hypothesize that these variables will improve from baseline to 6 months as a function of treatment intensity. A3. To test the effects of the treatments on methadone treatment outcomes including methadone dose changes and continued use of illicit drugs, as measured by urine toxicologies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SMOKING CESSATION: THE ROLE OF WITHDRAWAL & DEPENDENCE Principal Investigator & Institution: Xian, Hong; Medicine; Washington University Lindell and Skinker Blvd St. Louis, MO 63130 Timing: Fiscal Year 2001; Project Start 10-AUG-2000; Project End 31-JUL-2002 Summary: (Applicant's abstract): Failed smoking cessation is a major public health concern because cigarette smoking is the single most important cause of cancer mortality 'in the United States. The goal of this proposal is to examine the impact of nicotine dependence and nicotine withdrawal on the risk for failed smoking cessation in a genetically informative design. We will determine the risk for symptoms of nicotine dependence and withdrawal among successful quitters as compared to failed quitters in a cohort of approximately 4,000 twin pairs of the Vietnam Era Twin (VET) Registry. We will use twin data to estimate the genetic and environmental influences to each symptom of nicotine dependence and withdrawal and the degree to which these influences overlap for risk of failed smoking cessation. We will use latent class analysis to develop dependence and withdrawal profiles and test whether different profiles are predictive of the risk for failed smoking cessation. Finally, we will estimate the genetic and environmental influences to nicotine dependence and nicotine withdrawal profiles that overlap the risk for failed smoking cessation. The VET Registry is a valuable resource for this proposed secondary data analysis because it is a large, nationally distributed, community sample in which a high proportion of members have a history of smoking, failed cessation, nicotine dependence and nicotine withdrawal. This unique
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sample will provide the power to conduct complex latent class and behavior genetic analysis in a large cohort of middle-aged males. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SMOKING, BRAIN FUNCTION AND OUTCOME IN ADOLESCENTS Principal Investigator & Institution: Jacobsen, Leslie K.; Assistant Professor; Psychiatry; Yale University 47 College Street, Suite 203 New Haven, CT 065208047 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2005 Summary: (provided by the applicant) Adolescent initiation of tobacco use remains a major public health problem. With nearly 35 percent of high school students currently using tobacco, it is estimated that 5 million children living today will die prematurely as adults due to initiation of tobacco use during adolescence. The high rates of initiation of tobacco use among teenagers is likely multifactorial. However, given the heightened educational demands encountered during adolescence, enhancement of brain function with tobacco use may pose a particularly compelling inducement to transition from infrequent to regular tobacco use. Nicotine has been shown to enhance performance on tests of attention and, in some cases, on tests of memory in nondeprived smokers and in nonsmokers. Enhancement of memory by nicotine may be restricted to infrequent tobacco users. In this proposal the relationship between the effect of recent tobacco use and of nicotine withdrawal on activation of neural circuits that mediate performance of tasks involving working memory and selective attention will be examined in adolescent tobacco users. The relationship between brain response to recent tobacco use and tobacco use outcome at one-year follow-up will then be assessed. Preliminary data from a functional magnetic resonance imaging (fMRI) study of adolescent tobacco users suggests that, relative to nicotine withdrawal, recent tobacco use is associated with greater activation of left prefrontal cortex during high verbal working memory load conditions and greater activation of right dorsolateral prefrontal cortex during high attention load conditions. We will test the hypothesis that greater change in brain activation in response to recent smoking relative to nicotine withdrawal is associated with progression of tobacco use (heavier use, greater degree of nicotine dependence, failure to achieve abstinence) at one year follow-up and that this relationship will be observed chiefly in subjects who used tobacco infrequently at study entry. The relationship between the degree of change cognitive performance (assessed prior to and during scanning) in response to recent tobacco use and tobacco use at one-year followup will also be examined. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SOCIETY FOR RESEARCH ON NICOTINE AND TOBACCO ANN MEETING Principal Investigator & Institution: Stitzer, Maxine L.; Professor of Behavioral Biology; Society for Research on Nicotine/Tobacco on Nicotine and Tobacco Middleton, WI 53562 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-MAR-2003 Summary: The Society for Research on Nicotine and Tobacco (SRNT) was founded in 1994 to address the need for coordinated scientific discourse on research related to the many direct effects of nicotine and tobacco, the use of tobacco products in our society, the features of tobacco dependence and treatments for tobacco dependence. It is the first national organization primarily devoted to promoting the conduct of research on nicotine and tobacco and disseminating findings from this research. It is a
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multidisciplinary organization including members whose interests range from neuroscience to tobacco policy. The SRNT will hold its sixth annual meeting in February, 2000 at the Crystal City Marriott in Arlington, VA. We are requesting partial support for this and subsequent annual meetings from NIDA through the conference grant mechanism. At the annual meetings, a mulitdisciplinary group of scientists, many of whom are funded by NIDA grants, will present talks, posters and symposia that will highlight the latest research on nicotine and tobacco in the areas of neuroscience, clinical pharmacology, treatment research, epidemiology and policy research. The work of new investigators will be highlighted via special oral sessions and awards programs. In addition, we plan to hold, in alternate years, a 1-day special topics meeting that will explore a timely research topic in more depth. In 2000 the special topics meeting will be on outcomes measurement for smoking cessation clinical trials. Overall, the SRNT annual meeting serves a valuable function by providing a forum for dissemination and discussion of the latest findings in nicotine and tobacco research and the opportunity for cross fertilization of ideas across specific research areas. Partial support of this meeting by NIDA would further highlight the agency's commitment to the importance of nicotine and tobacco research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STRUCTURE OF CYTOPLASMIC REGION OF LEUKOCYTE ANTIGEN RELATED (LAR) PROTEIN Principal Investigator & Institution: Frederick, Christin; Cornell University Ithaca Office of Sponsored Programs Ithaca, NY 14853 Timing: Fiscal Year 2001 Summary: The crystal structure of cytochrome P450cam complexed with (S)-nicotine has been determined at 2.3 resolution. (S)-nicotine has been extensively studied as a substrate of both bacterial P450cam and human P450 enzymes. Previous kinetic studies have examined (S)-nicotine binding to P450cam (Jones et al., 1993, J. Am. Chem. Soc. 115, 381-387.). These demonstrate that (S)-nicotine undergoes regiospecific monooxygenation at the pyrrolidine 5' carbon, implying that the molecule orients in the active site with the pyrrolidine ring close to the catalytic heme iron. In contrast, the crystal structure shows the nicotine molecule in a reversed orientation with the pyridine nitrogen coordinated with the heme iron. The is consistent with UV spectral studies, which indicate formation of a low-spin hexacoordinate iron upon nicotine binding to P450cam in solution (Ibid.). However, the pyrrolidine 5' carbon is approximately 8 from the heme iron in the crystal structure, indicating that this represents a nonproductive, though energetically favorable, binding mode. These findings will be presented at the 17th International Congress of Biology and Molecular Biology, August 1997, San FRancisco, and are being written up for publication (see below). Additional studies are now examining possible reorientation of the ligand for productive binding. These include examination of (S)-nicotine binding to P450cam in the presence of CO under reducing conditions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SYNTHETIC EXPLORATION OF CENTRAL NICOTINIC RECEPTORS Principal Investigator & Institution: Glassco, Williams S.; Pharmacology and Toxicology; Virginia Commonwealth University Richmond, VA 232980568 Timing: Fiscal Year 2001; Project Start 01-MAR-1999; Project End 28-FEB-2003
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Summary: A combination of pharmacological, molecular and physiological data suggest the presence of multiple subpopulations of nicotinic acetylcholine receptors (nAChR) in the central nervous system. To date, molecular biologists have identified eleven distinct nAChR subunits in neuronal tissue (five such subunits are believed to combine to form the functional nAChR), and over half a dozen different combinations of these subunits, when expressed together in various cell lines, produce functional, ligand-gated ion channels. However, only three distinct nAChRs can be identified using chemical ligands, and two of these are distinguished by polypeptide toxins. We have found differences between the structure-activity relationships (SARs) for various nicotinemediated in vivo effects and in vitro affinity. We propose to continue these studies by synthesizing and testing a series of 5- and 6- substituted isonicotines, and to compare these with the SARs of previously reported 5- and 6-substituted nicotines. We additionally propose to synthesize some isonicotine analogs with an ether link between the 3-positions of the pyridine and pyrrolidine rings. We also propose to study the SAR of substituents attached at the 2'- and 4- positions of nicotine, as well as to the comparable positions on a series of pyrrolidine ring-opened analogs of nicotine. Susceptibility to mecamylamine antagonism is a hallmark of agonists to the central nicotine high affinity site, but this may not be the case for some of the 2'- and 4substituted derivatives we are proposing. Additionally, we propose to synthesize analogs of trans-metanicotine, a central nicotine agonist with in vitro and in vivo selectivity, in which the carbon-carbon double bond off the 3-position of the pyridine ring is replaced by a bioisosteric sulfur atom. This modification will allow introduction of oxygen atoms (sulfoxide and/or sulfone) to mimic the structurally and pharmacologically similar pseudooxynicotine. We further propose to synthesize a series of N6-substituted 6- aminonicotines and 6-substituted nicotines as potential competitive nAChR antagonists. Key to these studies is a comprehensive approach to pharmacological evaluation of the various series of compounds. In vitro and in vivo evaluation will be needed for most of these compounds, as we have previously found instances where affinity and activity can vary independently of each other. We have a standard series of tests for evaluation of nicotine-like activity, including displacement of [3H]nicotine from rat brain, two functional assay using mice (inhibition of spontaneous activity and tail-flick antinociception) and drug discrimination using rats trained on nicotine. We additionally propose to utilize the newer in vitro expression systems to correlate selectivity with affinity for specific subunit combination using an oocyte expression systems (alpha4beta2, alpha3beta2). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TAILORED OUTPATIENTS
NICOTINE
REPLACEMENT
THERAPY
FOR
Principal Investigator & Institution: Boroff, Erika; Harvard Pilgrim Health Care, Inc. 93 Worcester St Wellesley, MA 02481 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 29-SEP-2004 Summary: (Provided by applicant): This project will test the feasibility of a physician and nurse run smoking cessation program that uses transdermal nicotine replacement therapy tailored to match precessation serum cotinine levels. Findings from the proposed pilot study will provide essential information for submission of an RO1 application for a randomized clinical trial. The specific aims of the proposed pilot are to obtain estimates of the: 1) accessibility and availability of subjects in a general internal medicine practice; 2) refusal rates and selection issues; 3) ease of adjusting patch doses based on a protocol; 4) ease of administration of counseling sessions and questionnaires;
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5) side effect profile of medications; 6) rates of adherence; 7) relationship between percent nicotine repletion and cessation rates; 8) identify all variables to be included in an application for a randomized controlled trial; 9) develop a database management system. Methodology: 1. Study design a six-month, prospective, double-blinded and randomized pilot study. 2. Subject recruitment--30 adults (15 intervention, 15 usual care), followed by internists at the Cleveland Clinic Foundation, who are currently smoking more than 15 cigarettes per day and have done so over the past six months; after the prospective subjects respond to an advertisement, they will be screened for readiness to change per the transtheoretical model of Prochaska and DiClemente. Patients in the preparation phase will be invited to a screening visit for a physical exam, ECG, and exhaled CO (carbon monoxide) level. 3. Intervention patients in the intervention group will have nicotine patch doses adjusted based on serum cotinine levels, whereas usual care patients will receive patch doses based on a standard protocol, regardless of cotinine levels. All patients will receive person-to-person counseling and telephone support by a nurse. 4. Outcomes measurements: 1) accessibility and availability of subjects in a general internal medicine practice; 2) refusal rates and selection issues; 3) ease of adjusting patch doses based on a protocol; 4) ease of administration of counseling sessions and questionnaires; 5) side effect profile of medications; 6) rates of adherence; 7) relationship between percent nicotine repletion and cessation rates (which will be confirmed by serum cotinine and exhaled CO). In addition, questionnaires will be used to assess quality of life and incidence of depressive symptoms at study?s beginning and end. Significance: Tobacco use has been implicated as the leading avoidable cause of morbidity and mortality in the Unites States. In addition to deleterious effects on the individual?s health, smoking incurs large societal costs as well. This pilot study will provide invaluable information on the feasibility of implementing a physician and nurse run smoking cessation intervention, applicable to general internal medicine practices, tailoring nicotine replacement therapy to varying levels of nicotine dependence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE DEPENDENCE
COLLABORATIVE
GENETIC
STUDY
OF
NICOTINE
Principal Investigator & Institution: Reich, Theodore; Professor of Psychiatry and Genetics; Psychiatry; Washington University Lindell and Skinker Blvd St. Louis, MO 63130 Timing: Fiscal Year 2001; Project Start 28-SEP-2001; Project End 31-AUG-2006 Summary: This is a resubmission of the Collaborative Genetic study of Nicotine Dependence (COGEND), a new five-year Program Project Grant to detect and evaluate familial and non-familial causes of nicotine dependence. The goals of the program are the identification of biological mechanisms, genes and environmental features that determine nicotine consumption and predispose or protect individuals from the onset and persistence of the disorder. Improved understanding of these factors will suggest novel, powerful strategies for reducing or eliminating nicotine dependence and the massive health burden it places on all societies. Subjects and families will be recruited from comparable HMOs at three sites; The Henry Ford Hospital (Detroit), The University of Minnesota (Minneapolis-St. Paul) and Washington University (St. Louis). There are three interrelated studies: (1) a genetic epidemiology study of the families of nicotine dependent individuals, (2) a genetic linkage and candidate gene study of nicotine of nicotine dependence and related phenotypes and (3) a neuropharmacology study of the relationship between nicotine dependence and related phenotypes and (3)
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a neuropharmacology study of the relationship between nicotine metabolism and tobacco consumption and dependence. Candidate gene studies include case- control and family based designs to maximize power and minimize bias due to ethnic stratification. African-Americans will be over-sampled to provide a sufficient sample for statistical consumption, nicotine metabolism and assessment of familial and non-familial variables in multiple domains that are correlated with the disorder. Data management and administrative cores support these studies. Each project contributes thematically to the program. The family epidemiology project elucidates environmental and familial factors from which informative quantitative and qualitative phenotypes are derived. The linkage and candidates gene studies include a genome-wide survey, fine mapping and case-control and family based candidate gene studies to identify genes that determine nicotine consumption, and susceptibility or protection from nicotine dependence. Their effect on the incidence and familial distribution of nicotine dependence and tobacco consumption will be studied in the large of probands, controls and relatives metabolism providing biological insight into disorder and endophenotypes and candidate genes for the genetic study. Metabolic variables will be used as co-variables in the family, population and linkage studies. A team of investigators from three centers will work together to unravel this disorder. Our team includes epidemiologists, geneticists, statisticians, psychiatrists, psychologists, and pharmacologists. We hope to translate these basic biological and environmental studies into strategies to reduce the massive health burden of nicotine dependence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE INFLUENCE OF NICOTINE ON FRACTIONATED REACTION TIME Principal Investigator & Institution: Marzilli, Thomas S.; Health/Leisure & Exercise Sci; University of West Florida 11000 University Pky Pensacola, FL 32514 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2005 Summary: (provided by applicant): This R03 grant, in response to NIDA's PAR-00-059 "Small Grant Program," will importantly support the implementation of exploratory research that incorporates a novel and extremely fine-grained approach to the study of nicotine and human performance. This innovative methodology uses electromyography to dissociate the central (cognitive) and peripheral (neuromuscular) processing related to the successful completion of a variety of reaction time tasks. To further discriminate at what level of the central processing stream nicotine is most likely to have an effect, a basic chronometric approach to studying information processing will be incorporated. This chronometric approach will allow for the independent examination of each of the three theoretically nonoverlapping information processing stages which include stimulus identification, response selection and response programming. This methodology provides the opportunity to investigate nicotine's effects on the time between the initiation of the stimulus and the initiation of the motor response (central processing) as well as the time delay between the initiation of the motor response and the actual movement or button release (neuromuscular processing) during a variety of reaction time tasks. This paradigm has been shown to be sensitive to a number of variables such as: intensity of stimulus, number of response alternatives, complexity of movement, age, physical activity and pathologies, but has yet to be used to investigate the affects of nicotine on movement preparation, initiation and execution. These methodologies are well grounded in the field of Motor Learning and Cognitive Psychology, and will be a definite addition to the literature in regards to nicotine effects on human performance. Moreover, the methodologies offered herein could have clinical
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payoffs in populations, such as Parkinson's disease, Huntington's disease and other pathologies where the planning of movement is thought to be intact, but the initiation of movement may be compromised. This laboratory-based project uses cigarette smokers to better understand how nicotine affects the individual components (pre-motor and motor time) of a variety of reaction time tasks. This disassociation of central and neuromuscular components within a reaction time paradigm offers a substantial positive deviation from previous research utilizing only simple or choice reaction time methodologies because it may be that individual task components are influenced differentially by nicotine, which would not be evident if only a single, summary measure of reaction time was used. This study will be accomplished by systematically varying experimenter supplied nicotinised and denicotinised cigarettes while administering a variety of subjective, physiological and performance measures under double blind, placebo controlled conditions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE ROLE OF NORNICOTINE IN PROTEIN GLYCATION Principal Investigator & Institution: Dickerson, Tobin J.; Scripps Research Institute 10550 N Torrey Pines Rd La Jolla, CA 920371000 Timing: Fiscal Year 2002; Project Start 01-NOV-2002; Project End 31-MAY-2004 Summary: (provided by applicant): Despite ample evidence supporting the negative effects of tobacco abuse, cigarettes and nicotine addiction remain one of the leading causes of preventable death in the United States. Both the systemic and psychoactive effects of nicotine are well-documented, yet little research has been devoted to the physiological effects of nornicotine, a minor psychoactive metabolite. We propose that nornicotine is capable of participating in the formation of glycation proteins, and that the presence of nornicotine both natively in tobacco and as a nicotine metabolite could have significant implications in a number of tobacco-related disease states. In order to explore the role of nornicotine in protein glycation, a multidisciplinary study is proposed. First, using synthetic organic chemistry, we will determine the ability of nornicotine to form Amadori products in vitro. Concurrently, we will develop a rapid immunoassay for the detection of nornicotine-derived glycated proteins. To facilitate this, we will also develop novel haptens for the preparation of new antibodies with enhanced specificity for these glycation products. This assay will be tested using a behavioral rat model of chronic exposure to nicotine, nornicotine, and the nornicotinederived Amadori product. Second, to establish the major route of introduction of Amadori products, we will explore both the rate of in vivo synthesis of the Amadori product versus the inherent proportion of this compound that exists in cured tobacco. We believe that the proposed studies will provide a molecular link between disease and tobacco abuse as well as a dramatic insight into the unprecedented ability of a secondary nicotine metabolite to perform chemistry in vivo. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: TRANSDERMAL SCHIZOPHRENICS
NICOTINE
AND
BUPROPION-SR
IN
Principal Investigator & Institution: Tidey, Jennifer W.; Ctr for Alcohol & Addict Studs; Brown University Providence, RI 02912 Timing: Fiscal Year 2001; Project Start 27-SEP-2001; Project End 31-JUL-2005 Summary: (provided by applicant) There is a high prevalence (60-88 percent) of cigarette smoking among people with schizophrenia, but few smoking cessation interventions
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have been developed for these patients. Little is known about factors that control smoking in this population or whether interventions that reduce cigarette smoking among the general population are effective in smokers with schizophrenia. Two pharmacotherapies that reduce smoking in the general population are transdermal nicotine and sustained release bupropion. Because of neurochemical dysfunction associated with schizophrenia, these pharmacotherapies may be less effective in smokers with schizophrenia. Clinical and experimental studies on the effects of nicotine replacement in smokers with schizophrenia have yielded equivocal results. Preliminary results from a single treatment study with sustained release bupropion appear promising. The studies in the present proposal are designed to examine under controlled laboratory conditions the effects of transdermal nicotine (0, 21, 42 mg/day) and sustained release bupropion (0, 150, 300 mg/day) on smoking in people with schizophrenia and non-schizophrenic controls. The effects of transdermal nicotine and sustained release bupropion on smoking topography measures, smoking urges, nicotine withdrawal symptoms and affect will be determined. These studies use within-subjects, repeated measures, placebo controlled designs. Together, they will provide muchneeded information on the biological, behavioral and subjective effects of transdermal nicotine and sustained release bupropion on smoking in people with schizophrenia. In turn, this information could contribute to the development of effective smoking cessation treatments for smokers with schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TRANSDERMAL NICOTINE TREATMENT OF MCI Principal Investigator & Institution: Newhouse, Paul A.; Professor; Psychiatry; University of Vermont & St Agric College 340 Waterman Building Burlington, VT 05405 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2006 Summary: (provided by applicant): A major thrust of clinical research in cognition and aging has been directed towards the identification and potential treatment of the preAlzheimer condition known as Mild Cognitive Impairment (MCI). Patients with amnestic MCI appeared to have a high risk of developing dementia, with 12- 15% per year progressing to the point where they meet criteria for Alzheimer's disease, and 5060% being diagnosed with dementia within five years. Developing effective treatments that will improve symptoms of memory loss and delay or retard the development of dementia in patients who are at high risk is an extremely important public health goal. A number of treatment approaches are being considered or tested including acetylcholinesterase inhibitors, high dose vitamins, hormones, etc. Alterations in brain systems that involve CNS nicotinic receptors appear to be critically important in the development of cognitive impairment resulting in dementia. Loss of nicotinic receptors is one of the most reliable receptor-based findings in Alzheimer's disease and this loss correlates with cognitive impairment. Blockade of nicotinic receptors in normals leads to reversible cognitive impairment in the same domains that are affected in MCI and Alzheimer's disease. Stimulation of nicotinic receptors with nicotine or and/or novel nicotinic agonists reliably improves certain aspects of attentional and memory functioning in both normal individuals, patients with ADHD, schizophrenia, patients with Alzheimer's disease, and in our preliminary studies, MCI patients. Nicotine is arguably the most well studied cognition-enhancing substance known, with hundreds of studies in both tobacco and non-tobacco forms. Furthermore, nicotinic stimulation appears to have significant neuroprotective effects and nicotinic stimulation may have positive influences on APP processing. We propose a pilot 6 month double-blind placebo-controlled trial of transdermal nicotine in 60 patients with amnestic MCI with a
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6-month open label extension. Our primary goal is to demonstrate that transdermal nicotine is safe to administer to the non-smoking MCI patients over a one year period. Our secondary goal is to demonstrate cognitive symptom relief/improvement and to gain some preliminary data regarding prevention of progression. Transdermal nicotine has proved to be a extremely safe method of administering nicotine that eliminates the liabilities of tobacco associated nicotine. Patients will be recruited, screened, and treated at 3 major medical centers by investigators who have been leaders in clinical and basic science nicotinic research. Subjects will be tested utilizing sophisticated computerized and non-computerized methodology. Close clinical follow-up will insure patient safety. For reasons outlined above, transdermal nicotine may be an excellent way of improving cognitive performance and delaying progression of MCI. If nicotine proves successful in alleviating cognitive symptoms and in improving global outcomes along with reasonable safety, we will propose a large multicenter clinical trial. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TRANSITION OF NICOTINE DEPENDENCE Principal Investigator & Institution: Difranza, Joseph R.; Professor; Family and Community Medicine; Univ of Massachusetts Med Sch Worcester Office of Research Funding Worcester, MA 01655 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2006 Summary: (provided by the applicant) Animal and human studies will be conducted in parallel to determine the threshold dosing for the first symptoms of nicotine dependence in adolescent humans and for the first neurochemical changes brought on by nicotine in the brains of adolescent rats. Separate experiments will evaluate the upregulation of high affinity nicotinic cholinergic receptors in the midbrain reward centers, and the activation of cholinergic reward pathways. These experiments will be conducted to explore the effects of low-dose intermittent exposure to nicotine, simulating the nicotine exposures commonly present at the onset of nicotine dependence in teenagers. A comparison will be made regarding the sensitivity of adolescent and adult rats to the neurochemical effects of nicotine that are thought to be responsible for dependence. Intermittent and continuous dosing will be compared and gender differences will be explored. Adolescents and adults will be compared in the speed with which neurochemical changes occur. In humans, a prospective longitudinal study employing 1200 subjects and individual interviews will be conducted to explore individual differences in the speed with which nicotine dependence develops. The nicotine dosing and pattern of use at the onset of the first symptoms and full dependence will be studied. Investigations will explore why some youths develop symptoms of dependence upon exposure to nicotine while others do not. A new theorybased measure of early dependence for youths will be tested against established measures of dependence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: TREATMENT OF ADDICTION TO NICOTINE IN SCHIZOPHRENIA Principal Investigator & Institution: Ziedonis, Douglas M.; Associate Professor and Director; Psychiatry; Univ of Med/Dent Nj-R W Johnson Med Sch Robert Wood Johnson Medical Sch Piscataway, NJ 08854 Timing: Fiscal Year 2003; Project Start 05-JUL-2003; Project End 30-JUN-2007 Summary: (provided by applicant): Over 75% of patients with schizophrenia are nicotine dependent, and most of them die of smoking related illnesses. Few are offered
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nicotine dependence treatment in primary care or mental health settings. Unfortunately there have been few clinical treatment studies, and there continues to be a great need to develop, test, and disseminate behavioral therapy and medication management approaches for nicotine dependence treatment in mental health settings. Treatment manuals, training programs, and clinical studies are needed. Such therapies should reflect the unique needs of this population, and be "real world applicable." This grant reapplication responds to the concerns and helpful suggestions of the initial Review Committee and proposes to further develop and pilot test our behavioral therapy approach of Treating Addiction to Nicotine in Schizophrenia (TANS). In response to the Review Committee, this reapplication clarifies and better links TANS to its the empirical foundation, addresses "real world applicability," changes the control treatment, and modifies the assessment battery. We propose to develop and test Stage 1 Therapy Development Products (therapy manual, adherence scales, and training program) of TANS and our new control treatment of Nicotine Dependence Medication Management by Mental Health Providers (Medication Management). We agree with the Review Committee's suggestion to compare TANS to a lower intensity control treatment in regards to (1) engagement, retention, and extended abstinence during the initial three months, (2) relapse prevention during months four through six, and (3) longer-term abstinence at later follow-ups. After an initial open trial of 20 subjects to develop the therapy products, we propose to do a larger study of 100 subjects randomized to TANS versus Medication Management. The proposed study is important because it will create two real world applicable psychosocial treatments that could help clinicians in the mental health system better address tobacco and researchers doing medication or Stage II therapy studies. The study will assess whether medication management is sufficient in this population, and whether lengthening treatment will improve long-term outcomes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TREATMENT OF NICOTINE DEPENDENT SMOKERS Principal Investigator & Institution: Hayes, Steven C.; Chair and Foundation Professor; Psychology; University of Nevada Reno Reno, NV 89557 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2004 Summary: Certain nicotine-dependent smokers smoke in order to modify or suppress unpleasant states such as negative affect and nicotine withdrawal. For these smokers, the immediate avoidance of troublesome thoughts, feelings, or sensations appears to take precedence over the known health risks associated with smoking. This proposal suggests a treatment model for nicotine-dependent smokers derived from the experimental literature on suppression, acceptance, and social support. This biobehavioral model is applied to the hypothesized mechanism of action in slow release bupropion, a promising new treatment for smoking cessation. A psychosocial component using social support to facilitate acceptance skills training for nicotinedependent smokers is proposed. It is hypothesized that acceptance, suppression, and insession social support may mediate treatment effects and moderate the impact of withdrawal symptoms and negative affect on treatment outcome. The specific aims are (a) to use the Experiential Acceptance and Support model to generate a manual integrating relevant interventions from Acceptance and Commitment Therapy and Functional Analytic Psychotherapy, to be used as a psychosocial component in the treatment of nicotine-dependent smokers, (b) to investigate theory-specified variables that may reflect on the putative mechanisms underlying the proposed treatment and slow release bupropion, (c) to pilot the combined treatment, (d) to evaluate the role of withdrawal symptoms and negative affect on treatment process and outcome, (d) to
146 Nicotine
evaluate the clinical acceptability of the proposed treatment, and (e) to generate data to use in a power analysis for future studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TREATMENTS MECHANISMS
FOR
NICOTINE
DEPENDENCE:
BRAIN
Principal Investigator & Institution: Brody, Arthur L.; Associate Professor - in Residence; Brentwood Biomedical Research Institute Bldg. 114, Room 218 Los Angeles, CA 90073 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2006 Summary: (provided by applicant): Despite new medication options for nicotine dependence, abstinence rates after 6 months or more of treatment remain relatively low at 14 to 35.5%. Because severity of craving has repeatedly been linked with relapse in smokers attempting abstinence, a possible route to the development of more effective treatments for nicotine dependence is through a better understanding of the neurobiological substrates of current successful treatments that reduce craving and cigarette usage. Recent brain imaging work from our group demonstrates that exposure of heavy cigarette smokers to cigarette related (compared with neutral) cues results in increases in both the intensity of craving and normalized metabolism in the anterior cingulate gyrus spanning the midline and left posterior orbitofrontal cortex. Additionally, intensity of cigarette craving was significantly positively correlated with relative metabolism in the bilateral OFC, dorsolateral prefrontal cortex, anterior insula, and right somatosensory cortex. These findings are consistent with studies of craving for other drugs that produce dependence (cocaine, opiates, and alcohol). In this proposal, 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) will be used to assess regional brain metabolism associated with cigarette craving both before and after two distinct forms of treatment for nicotine dependence in order to examine the brain mechanisms of these treatments. Subjects meeting full DSM-IV criteria for nicotine dependence will undergo 2 FDG-PET scans (one during exposure to cigarette-related cues and the other during exposure to neutral cues) both before and after treatment with either bupropion HCI with no concomitant counseling, structured practical group counseling (using relapse prevention techniques) with no concomitant medication, or pill placebo. The goals of this study are: (1) to determine changes in regional cerebral metabolic activation during presentation of cigarette-related cues from pre- to posttreatment with either bupropion HCI, practical group counseling, or placebo, (2) to determine changes in cue-induced cigarette craving from pre- to post- treatment with either bupropion HCI, practical group counseling, or placebo, and determine brain metabolic correlates of changes in cue-induced craving, (3) to determine changes in regional metabolism in the neutral state from pre- to post- treatment with either bupropion HCI or practical group counseling and (4) to determine pre- treatment regional brain metabolic predictors of response to bupropion HCI and practical group counseling. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: UPREGULATION OF NICOTINIC RECEPTORS Principal Investigator & Institution: Green, William N.; Associate Professor; Neurobiology/Pharmacology/Phys; University of Chicago 5801 S Ellis Ave Chicago, IL 60637 Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 31-MAY-2006
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Summary: Adapted from applicant's abstract): Tobacco smoking is a major health problem leading each year to $50 billion dollars in health costs and 400,000 deaths in the United States. Significant evidence indicates that nicotine is the component in tobacco leading to abuse and addiction. Nicotine binds to nicotinic receptors found in the brain. To characterize the molecular biology of nicotine addiction, our research will focus on nicotinic receptors in the brain and how nicotine-induced changes in nicotinic receptors correlates with aspects of addiction. Like other drugs of abuse, many of the addictive effects of nicotine appear to result from the stimulation dopaminergic, mesolimbic neurons, in particular dopaminergic neurons from the ventral tegmental area (VTA). The short-term effects of nicotine are caused by the activation of nicotinic receptors on these neurons. Long-term exposure to nicotine enhances or "sensitizes" the response of these neurons to nicotine, which correlates with the enhancement or "upregulation" of high-affinity binding to nicotinic receptors. The goals of this application are: 1) to identify receptor subtypes involved in nicotine upregulation, 2) to identify the mechanisms that cause nicotine upregulation of nicotinic receptors and 3) to test whether nicotinic receptor upregulation by nicotine is involved in the sensitization of the response to nicotine. The hypotheses to be tested are that: 1) at nicotine concentrations achieved during smoking, the upregulation of nicotinic receptors is primarily an upregulation of alpha4beta2-containing receptors; 2) nicotinic receptor upregulation in vivo is caused by a receptor state change that causes the receptors to enter a hypersensitive state; 3) sensitization of the nicotine response of VTA neurons is caused, at least in part, by receptor upregulation. Several possible nicotinic subunit combinations will be expressed to test whether upregulation occurs for each combination and the extent to which upregulation is a change in receptor number or entry into a hypersensitive state. After, the experiment will be extended to cells expressing "native" nicotinic receptors of unknown subunit composition, including PC12 rat pheochromocytoma cells, mouse N1E-115 neuroblastoma cells, and VTA neurons. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: USAGE PATTERNS OF OTC NICOTINE PATCHES: CONSUMER SURVEY Principal Investigator & Institution: Shi, Chih-Wen; Family and Preventive Medicine; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, CA 92093 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 30-JUN-2008 Summary: (provided by applicant): BACKGROUND: Since 1996, several forms of nicotine replacement therapies (NRTs) have switched from prescription to over-thecounter (OTC) status, allowing the public to wean off nicotine dependence without physician supervision. While the use of prescription NRTs (e.g. nicotine patches) has been extensively studied, little is known about how the public uses OTC NRTs in the real-world setting. To address this gap, we propose to perform the first exploratory U.S. consumer survey in an attempt to provide a "snapshot" of the ways in which the public is using OTC nicotine patches. SPECIFIC AIMS: 1) To describe the characteristics of the OTC nicotine patch consumers and their use patterns, and 2) To determine the factors associated with inappropriate use of OTC nicotine patches. METHODS: We propose to perform a cross-sectional survey of consumers (N=600) purchasing OTC nicotine patches in a stratified random sample of 30 retail pharmacies throughout Los Angeles County. In each pharmacy, participants will be recruited through shelf advertisements and will be asked to complete a self-administered, anonymous questionnaire containing these domains--demographics, smoking history, past medical history, other concurrent
148 Nicotine
cessation methods, choice and previous use of NRT products, and factors influencing decision to purchase OTC nicotine patch. Explicit criteria for appropriateness of OTC nicotine use will be derived from medical literature and the indications and contraindications as per the package labels. SIGNIFICANCE: This study will 1) establish a novel community pharmacy-based data collection method, 2) raise physician awareness of how patients use OTC nicotine patches, and 3) provide the Food and Drug Administration (FDA) with post-marketing surveillance information regarding actual consumer usage patterns as compared to the intended use guidelines. This K23 Mentored Patient-Oriented Research Career Development Award will allow Dr. Shi to obtain a PhD in Health Services/Pharmaceutical Economics and Policy while performing an original mentored research project. These training experiences will help her consolidate the essential skills, knowledge, and collegial networks for establishing an academic health services research career and will further poise her expertise in topics and policies regarding over-the-counter medications. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: VACCINATION FOR TREATMENT OF NICOTINE DEPENDENCE Principal Investigator & Institution: Malin, David Biopharmaceuticals 12276 Wilkins Ave Rockville, MD 20852
H.;
Professor;
Nabi
Timing: Fiscal Year 2001 Summary: This project is part of an ongoing multi-laboratory effort to evaluate the potential of immunization against nicotine to aid in smoking cessation. The nicotine conjugate immunogen, developed by Nabi, is 3'- aminomethylnicotine-rEPA. The particular role of this laboratory has been to evaluate whether sufficient immunization could be achieved to eliminate a variety of nicotine's behavioral and physiological effects. Passive immunization with IgG from anti-sera raised against this immunogen has largely eliminated the pressor effect of nicotine, the locomoter activating effect and the ability of nicotine to relieve nicotine abstinence syndrome (all at nicotine mg/kg doses higher than those consumed by smokers). Preliminary data suggests that active immunization can significantly reduce the nicotine pressor effect. All this is consistent with data from Dr. Pentel's laboratory demonstrating that immunization profoundly interferes with nicotine distribution. In anticipation of clinical studies, Nabi will prepare a Clinical (or GMP) Lot of immunogen and our own laboratory will address several issues of preclinical relevance. Can antibodies raised against the Clinical Lot of immunogen prevent various nicotine actions in a manner similar to that already demonstrated for antibodies raised against the research lot? Can active immunization, discriminative stimulus properties and the initial induction of nicotine dependence? In the cases of cardiovascular and locomoter actions, does the Clinical Lot of immunogen have similar effects to those found initially with the Research Lot? Several studies address the possible use of immunization prior to smoking cessation and during ongoing nicotine consumption. Will passive immunization or active immunization precipitate nicotine abstinence signs during ongoing nicotine infusion? Or will the gradual onset of immunization result in equally gradual waning of dependence, so as to attenuate the subsequent abstinence syndrome once nicotine is abruptly discontinued? In several experiments, samples of serum and brain tissue will be obtained and shipped to Dr. Pentel (another project leader) for analysis of antibody concentration and affinity as well as serum and brain nicotine levels. These joint experiments are intended to increase our understanding of the quantitative relationships between antibody levels, changes in nicotine distribution and modulation of nicotine pharmacodynamic effects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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•
Project Title: VACCINATION FOR TREATMENT OF NICOTINE DEPENDENCE Principal Investigator & Institution: Hatsukami, Dorothy K.; Professor of Psychiatry; Nabi Biopharmaceuticals 12276 Wilkins Ave Rockville, MD 20852 Timing: Fiscal Year 2001 Summary: Cigarette smoking is one of the most significant public health concerns facing this nation as well as countries abroad. The prevalence and impact of tobacco use are greater than any other drugs of abuse. Many current smokers want to quit smoking, however few are successful when they quit on their own. Furthermore, even with intensive behavioral effectiveness of these treatments among a broad-based population of smokers is likely to be even less. In order to address this public health concern, innovative, easily administered treatment must be developed. In the past three years, investigators in our laboratory and at Texas have been testing the effects of a nicotine vaccine in animal studies. The results from these studies look very promising. These studies have characterized a highly immunogenic vaccine that elicits nicotine-specific antibodies of high affinity and specificity, a significant reduction in the distribution of nicotine to the brain even with repeated doses of nicotine, and a reduction in locomoter activity, blood pressure, and ACTH release in response to nicotine. In addition, immunization was observed to block the effects of nicotine in relieving withdrawal symptoms. Two human studies of this vaccine are proposed that will be conducted in the third and fourth year of the grant period after further animal toxicity and efficacy studies. The goal of the of the first study will be to determine the immunogenicity, safety and preliminary efficacy of the nicotine of the nicotine vaccine among smokers among smokers and ex-smokers randomly assigned in a double-blind manner to one of the three doses of nicotine vaccine or placebo. The primary outcome measures are the concentration and affinity of antibody titers, time and number of doses to achieve maximum nicotine specific antibody titers and safety. The results of this study will help determine the dose and number of booster doses to be used in the subsequent study. This second study will be a clinical trial to determine the efficacy of the nicotine vaccine as a smoking cessation aid. Smokers (N=300) will be randomly assigned to active nicotine vaccine or placebo vaccine and will be seen on a regular basis for the first 8 weeks and at 12 and 26 weeks after the primary vaccination. The primary outcome measures will be 4 weeks of continuous abstinence at the end of treatment and prevalence of sustained abstinence. The results from this study will address whether this nicotine vaccine will be a feasible and effective treatment for nicotine dependence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: VACCINATION FOR TREATMENT OF NICTOTINE DEPENDENCE Principal Investigator & Institution: Fattom, Ali I.; Vice President, Research; Nabi Biopharmaceuticals 12276 Wilkins Ave Rockville, MD 20852 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-MAR-2004 Summary: A nicotine vaccine (NincVax or 3'-immunogen) has been developed which elicits high titers of nicotine-specific antibodies in experimental animals. Immunization of rats substantially reduces the fraction of a nicotine dose reaching the brain, prevents nicotine-induced increases in blood pressure, prevents nicotine-induced stimulation of locomoter activity, and inhibits the relief of mediated behaviors relevant to nicotine dependence. These effects are observed at clinically relevant nicotine doses, and with nicotine-specific IgG titers that should be achievable in humans. The current proposal is one of four components of this SPIRCAP application, the purpose of which is to perform late preclinical and human clinical studies evaluating vaccination against nicotine as a
150 Nicotine
potential treatment for nicotine dependence. The individual and human clinical studies evaluating vaccination against nicotine as a potential treatment for nicotine dependence. The individual components of the SPIRCAP application are 1) Development and manufacturing for clinical studies and serological testing (Dr. Fattom, Nabi, Rockville), 2) Behavioral studies of vaccination in rats (Dr. Malin, U. HoustonClear Lake), 3) Pharmacokinetic and additional behavioral studies of vaccination in rats (Dr. Pentel, Minneapolis Medical Research Foundation) and 4) Phase I/II and III clinical trials of vaccination (Dr. Hatsukami, U. Minnesota). An Administrative Core will provide overall coordination and administrative support for the project (Dr. Scott Winston, Nabi, Rockville). In addition, toxicology studies of the nicotine vaccine will be performed under a separate contract with NIDA. The aims of this component of the SPIRCAP are to: 1) Manufacture two clinical lots of NicVax 2) Perform preclinical safety and toxicology studies 3) Prepare and submit IND for human clinical studies 4) Perform serological testing on preclinical and clinical samples 5) Conduct clinical site and data monitoring in support of the human clinical studies Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “nicotine” (or synonyms) into the search box. This search gives you access to fulltext articles. The following is a sample of items found for nicotine in the PubMed Central database: •
[beta]2 nicotinic acetylcholine receptor subunit modulates protective responses to stress: A receptor basis for sleep-disordered breathing after nicotine exposure. by Cohen G, Han ZY, Grailhe R, Gallego J, Gaultier C, Changeux JP, Lagercrantz H. 2002 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130623
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2[prime prime or minute]-Hydroxylation of nicotine by cytochrome P450 2A6 and human liver microsomes: Formation of a lung carcinogen precursor. by Hecht SS, Hochalter JB, Villalta PW, Murphy SE. 2000 Nov 7; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18791
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Abstinence from smoking eight years after participation in randomised controlled trial of nicotine patch. by Yudkin P, Hey K, Roberts S, Welch S, Murphy M, Walton R. 2003 Jul 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=164239
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Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.
With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.
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Blood-Brain Barrier Penetration Abolished by N-Methyl Quaternization of Nicotine. by Oldendorf WH, Stoller BE, Harris FL. 1993 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=45649
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Companies moving to market nicotine's medicinal qualities. by [No authors listed]; 2001 Oct 30; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=81597
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Corticotropin-releasing factor-binding protein ligand inhibitor blunts excessive weight gain in genetically obese Zucker rats and rats during nicotine withdrawal. by Heinrichs SC, Lapsansky J, Behan DP, Chan RK, Sawchenko PE, Lorang M, Ling N, Vale WW, De Souza EB. 1996 Dec 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26429
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Effect of nicotine on brain activation during performance of a working memory task. by Ernst M, Matochik JA, Heishman SJ, Van Horn JD, Jons PH, Henningfield JE, London ED. 2001 Apr 10; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=31902
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Effect of nicotine on secretory component synthesis by secretory epithelial cells. by Gregory RL, Gfell LE. 1996 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=170410
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Functional and Developmental Studies of the Peripheral Arterial Chemoreceptors in Rat: Effects of Nicotine and Possible Relation to Sudden Infant Death Syndrome. by Holgert H, Hokfelt T, Hertzberg T, Lagercrantz H. 1995 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41382
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Functional Characterization of a Nonclassical Nicotine Receptor Associated with Inositolphospholipid Breakdown and Mobilization of Intracellular Calcium Pools. by Garnier M, Lamacz M, Tonon MC, Vaudry H. 1994 Nov 22; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=45308
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Gene Cluster on pAO1 of Arthrobacter nicotinovorans Involved in Degradation of the Plant Alkaloid Nicotine: Cloning, Purification, and Characterization of 2,6Dihydroxypyridine 3-Hydroxylase. by Baitsch D, Sandu C, Brandsch R, Igloi GL. 2001 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=95407
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Gene expression in tobacco low-nicotine mutants. by Hibi N, Higashiguchi S, Hashimoto T, Yamada Y. 1994 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=160471
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General Practitioners' views on the provision of nicotine replacement therapy and bupropion. by McEwen A, West R, Owen L. 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=59675
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How much does relapse after one year erode effectiveness of smoking cessation treatments? Long term follow up of randomised trial of nicotine nasal spray. by Stapleton JA, Sutherland G, Russell MA. 1998 Mar 14; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28486
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Molecular Interactions between the Specialist Herbivore Manduca sexta (Lepidoptera, Sphingidae) and Its Natural Host Nicotiana attenuata. IV. InsectInduced Ethylene Reduces Jasmonate-Induced Nicotine Accumulation by Regulating Putrescine N-Methyltransferase Transcripts. by Winz RA, Baldwin IT. 2001 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88874
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Nicotine exposure and bronchial epithelial cell nicotinic acetylcholine receptor expression in the pathogenesis of lung cancer. by Minna JD. 2003 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151841
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Nicotine nasal spray with nicotine patch for smoking cessation: randomised trial with six year follow up. by Blondal T, Gudmundsson LJ, Olafsdottir I, Gustavsson G, Westin A. 1999 Jan 30; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27708
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Open randomised trial of intermittent very low energy diet together with nicotine gum for stopping smoking in women who gained weight in previous attempts to quit. by Danielsson T, Rossner S, Westin A. 1999 Aug 21; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28202
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Opioid and Nicotine Receptors Affect Growth Regulation of Human Lung Cancer Cell Lines. by Maneckjee R, Minna JD. 1990 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=53886
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Rapid Akt activation by nicotine and a tobacco carcinogen modulates the phenotype of normal human airway epithelial cells. by West KA, Brognard J, Clark AS, Linnoila IR, Yang X, Swain SM, Harris C, Belinsky S, Dennis PA. 2003 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151834
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Sequence of the 165-Kilobase Catabolic Plasmid pAO1 from Arthrobacter nicotinovorans and Identification of a pAO1-Dependent Nicotine Uptake System. by Igloi GL, Brandsch R. 2003 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=150138
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Smoking reduction with oral nicotine inhalers: double blind, randomised clinical trial of efficacy and safety. by Bolliger CT, Zellweger JP, Danielsson T, van Biljon X, Robidou A, Westin A, Perruchoud AP, Sawe U. 2000 Aug 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27447
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Structural model of nicotinic acetylcholine receptor isotypes bound to acetylcholine and nicotine. by Schapira M, Abagyan R, Totrov M. 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=65631
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Updating a systematic review -- what difference did it make? Case study of nicotine replacement therapy. by Stead LF, Lancaster T, Silagy CA. 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=60653
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The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with nicotine, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “nicotine” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for nicotine (hyperlinks lead to article summaries): •
A combination of exhaled carbon monoxide (CO) measurement and the Fagerstrom Test for Nicotine Dependence (FTND) is recommended to complete information on smoking rates in population-based surveys. Author(s): Groman E, Bayer P. Source: Sozial- Und Praventivmedizin. 2000; 45(5): 226-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11081241&dopt=Abstract
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A common genetic defect in nicotine metabolism decreases risk for dependence and lowers cigarette consumption. Author(s): Tyndale RF, Pianezza ML, Sellers EM. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 1999; 1 Suppl 2: S63-7; Discussion S69-70. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11768189&dopt=Abstract
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A comparison of a nicotine sublingual tablet and placebo for smoking cessation. Author(s): Glover ED, Glover PN, Franzon M, Sullivan CR, Cerullo CC, Howell RM, Keyes GG, Nilsson F, Hobbs GR. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2002 November; 4(4): 441-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12521403&dopt=Abstract
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A critical view of past NIH research funding on tobacco and nicotine. Author(s): Hughes JR, Liguori A. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2000 May; 2(2): 117-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11072449&dopt=Abstract
PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.
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A factor analysis of the Fagerstrom Test for Nicotine Dependence (FTND). Author(s): Radzius A, Gallo JJ, Epstein DH, Gorelick DA, Cadet JL, Uhl GE, Moolchan ET. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2003 April; 5(2): 255-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745499&dopt=Abstract
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A functional role for nicotine in Bcl2 phosphorylation and suppression of apoptosis. Author(s): Mai H, May WS, Gao F, Jin Z, Deng X. Source: The Journal of Biological Chemistry. 2003 January 17; 278(3): 1886-91. Epub 2002 November 05. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12421819&dopt=Abstract
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A pharmacokinetic crossover study to compare the absorption characteristics of three transdermal nicotine patches. Author(s): Fant RV, Henningfield JE, Shiffman S, Strahs KR, Reitberg DP. Source: Pharmacology, Biochemistry, and Behavior. 2000 November; 67(3): 479-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11164075&dopt=Abstract
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A pilot controlled trial of transdermal nicotine in the treatment of attention deficit hyperactivity disorder. Author(s): Shytle RD, Silver AA, Wilkinson BJ, Sanberg PR. Source: World J Biol Psychiatry. 2002 July; 3(3): 150-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12478880&dopt=Abstract
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A randomized, double-blind, placebo-controlled clinical evaluation of a nicotine sublingual tablet in smoking cessation. Author(s): Wallstrom M, Nilsson F, Hirsch JM. Source: Addiction (Abingdon, England). 2000 August; 95(8): 1161-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11092064&dopt=Abstract
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A receptor-mediated mechanism of nicotine toxicity in oral keratinocytes. Author(s): Arredondo J, Nguyen VT, Chernyavsky AI, Jolkovsky DL, Pinkerton KE, Grando SA. Source: Laboratory Investigation; a Journal of Technical Methods and Pathology. 2001 December; 81(12): 1653-68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11742036&dopt=Abstract
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A study of a new TSM bio-mimetic sensor using a molecularly imprinted polymer coating and its application for the determination of nicotine in human serum and urine. Author(s): Tan Y, Yin J, Liang C, Peng H, Nie L, Yao S. Source: Bioelectrochemistry (Amsterdam, Netherlands). 2001 March; 53(2): 141-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11339299&dopt=Abstract
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A study of the psychometric and predictive properties of the Fagerstrom Test for Nicotine Dependence in a population of young smokers. Author(s): Haddock CK, Lando H, Klesges RC, Talcott GW, Renaud EA. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 1999 March; 1(1): 59-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11072389&dopt=Abstract
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A vaccine for nicotine dependence: targeting the drug rather than the brain. Author(s): Pentel P, Malin D. Source: Respiration; International Review of Thoracic Diseases. 2002; 69(3): 193-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12097758&dopt=Abstract
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Abstinence effects and reactivity to nicotine during 11 days of smoking deprivation. Author(s): Pomerleau OF, Pomerleau CS, Marks JL. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2000 May; 2(2): 149-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11072453&dopt=Abstract
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Abstinence from smoking eight years after participation in randomised controlled trial of nicotine patch. Author(s): Yudkin P, Hey K, Roberts S, Welch S, Murphy M, Walton R. Source: Bmj (Clinical Research Ed.). 2003 July 5; 327(7405): 28-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12842953&dopt=Abstract
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Accelerated metabolism of nicotine and cotinine in pregnant smokers. Author(s): Dempsey D, Jacob P 3rd, Benowitz NL. Source: The Journal of Pharmacology and Experimental Therapeutics. 2002 May; 301(2): 594-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11961061&dopt=Abstract
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Activation of phospholipases A2 and D of a human neuroblastoma cell line (LA-N-2) by N-dodecyl-L-lysine amide (compound 24), a putative G protein activator: characteristics of inhibition by (-)-nicotine. Author(s): Garnham BM, Fitzpatrick-Wong S, Schunack W, Nurnberg B, Sorrentino G, Parkinson FE, Kanfer JN, Sitar DS. Source: Neurochemical Research. 2002 December; 27(12): 1613-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12515313&dopt=Abstract
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Acute cardiac effects of nicotine in healthy young adults. Author(s): Jolma CD, Samson RA, Klewer SE, Donnerstein RL, Goldberg SJ. Source: Echocardiography (Mount Kisco, N.Y.). 2002 August; 19(6): 443-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12356338&dopt=Abstract
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Acute effects of nicotine and mecamylamine on tobacco withdrawal symptoms, cigarette reward and ad lib smoking. Author(s): Rose JE, Behm FM, Westman EC. Source: Pharmacology, Biochemistry, and Behavior. 2001 February; 68(2): 187-97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11267622&dopt=Abstract
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Acute effects of nicotine withdrawal syndrome in pilots during flight. Author(s): Giannakoulas G, Katramados A, Melas N, Diamantopoulos I, Chimonas E. Source: Aviation, Space, and Environmental Medicine. 2003 March; 74(3): 247-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12650272&dopt=Abstract
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Acute myocardial infarction soon after nicotine replacement therapy. Author(s): Mathew TP, Herity NA. Source: Qjm : Monthly Journal of the Association of Physicians. 2001 September; 94(9): 503-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11528015&dopt=Abstract
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Acute nicotine reinforcement, but not chronic tolerance, predicts withdrawal and relapse after quitting smoking. Author(s): Perkins KA, Broge M, Gerlach D, Sanders M, Grobe JE, Cherry C, Wilson AS. Source: Health Psychology : Official Journal of the Division of Health Psychology, American Psychological Association. 2002 July; 21(4): 332-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12090675&dopt=Abstract
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Addiction professionals' attitudes regarding treatment of nicotine dependence. Author(s): Gill BS, Bennett DL. Source: Journal of Substance Abuse Treatment. 2000 December; 19(4): 317-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11281125&dopt=Abstract
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Adolescent nicotine dependence and smoking cessation outcomes. Author(s): Horn K, Fernandes A, Dino G, Massey CJ, Kalsekar I. Source: Addictive Behaviors. 2003 June; 28(4): 769-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12726789&dopt=Abstract
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Adolescent nicotine use. Author(s): McGee R, Williams S, Reeder AI. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2003 March; 42(3): 265. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12595777&dopt=Abstract
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Advances in neuroscience and pharmacology of nicotine. 3rd SRNT Europe Conference, Paris, France, 19-22 September 2001. Author(s): Balfour D, Le Houezec J. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2002 May; 4(2): 229-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12028855&dopt=Abstract
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Adverse effects of arecoline and nicotine on human periodontal ligament fibroblasts in vitro. Author(s): Chang YC, Lii CK, Tai KW, Chou MY. Source: Journal of Clinical Periodontology. 2001 March; 28(3): 277-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11284543&dopt=Abstract
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Alteration of the behavioral effects of nicotine by chronic caffeine exposure. Author(s): Tanda G, Goldberg SR. Source: Pharmacology, Biochemistry, and Behavior. 2000 May; 66(1): 47-64. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10837843&dopt=Abstract
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An animal model of adolescent nicotine exposure: effects on gene expression and macromolecular constituents in rat brain regions. Author(s): Trauth JA, Seidler FJ, Slotkin TA. Source: Brain Research. 2000 June 9; 867(1-2): 29-39. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10837795&dopt=Abstract
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An association study of DRD5 with smoking initiation and progression to nicotine dependence. Author(s): Sullivan PF, Neale MC, Silverman MA, Harris-Kerr C, Myakishev MV, Wormley B, Webb BT, Ma Y, Kendler KS, Straub RE. Source: American Journal of Medical Genetics. 2001 April 8; 105(3): 259-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11353446&dopt=Abstract
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An immunotherapeutic program for the treatment of nicotine addiction: hapten design and synthesis. Author(s): Isomura S, Wirsching P, Janda KD. Source: The Journal of Organic Chemistry. 2001 June 15; 66(12): 4115-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11397142&dopt=Abstract
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An investigation into the effect and mechanisms of action of nicotine in inflammatory bowel disease. Author(s): Sykes AP, Brampton C, Klee S, Chander CL, Whelan C, Parsons ME. Source: Inflammation Research : Official Journal of the European Histamine Research Society . [et Al.]. 2000 July; 49(7): 311-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10959551&dopt=Abstract
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An investigation of predictors of nicotine abstinence in a smoking cessation treatment study of smokers with a past history of alcohol dependence. Author(s): Kalman D, Tirch D, Penk W, Denison H. Source: Psychology of Addictive Behaviors : Journal of the Society of Psychologists in Addictive Behaviors. 2002 December; 16(4): 346-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12503909&dopt=Abstract
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Anabasine and anatabine as biomarkers for tobacco use during nicotine replacement therapy. Author(s): Jacob P 3rd, Hatsukami D, Severson H, Hall S, Yu L, Benowitz NL. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 2002 December; 11(12): 1668-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12496059&dopt=Abstract
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Anxiety sensitivity, self-reported motives for alcohol and nicotine use, and level of consumption. Author(s): Novak A, Burgess ES, Clark M, Zvolensky MJ, Brown RA. Source: Journal of Anxiety Disorders. 2003; 17(2): 165-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12614660&dopt=Abstract
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Applying the risk/use equilibrium: use medicinal nicotine now for harm reduction. Author(s): Kozlowski LT, Strasser AA, Giovino GA, Erickson PA, Terza JV. Source: Tobacco Control. 2001 September; 10(3): 201-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11544374&dopt=Abstract
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Are higher doses of nicotine replacement more effective for smoking cessation? Author(s): Hughes JR, Lesmes GR, Hatsukami DK, Richmond RL, Lichtenstein E, Jorenby DE, Broughton JO, Fortmann SP, Leischow SJ, McKenna JP, Rennard SI, Wadland WC, Heatley SA. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 1999 June; 1(2): 169-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11072398&dopt=Abstract
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Assessing nicotine dependence. Author(s): Rustin TA. Source: American Family Physician. 2000 August 1; 62(3): 579-84, 591-2. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10950214&dopt=Abstract
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Assessing the impact of a nurse-led health education intervention for people with peripheral vascular disease who smoke: the use of physiological markers, nicotine dependence and withdrawal. Author(s): Galvin K, Webb C, Hillier V. Source: International Journal of Nursing Studies. 2001 February; 38(1): 91-105. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11137727&dopt=Abstract
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Assessment of chronic exposure to cigarette smoke and its change during pregnancy by segmental analysis of maternal hair nicotine. Author(s): Pichini S, Garcia-Algar O, Munoz L, Vall O, Pacifici R, Figueroa C, Pascual JA, Diaz D, Sunyer J. Source: Journal of Exposure Analysis and Environmental Epidemiology. 2003 March; 13(2): 144-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12679794&dopt=Abstract
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Assessment of nicotine dependence symptoms in adolescents: a comparison of five indicators. Author(s): O'Loughlin J, DiFranza J, Tarasuk J, Meshefedjian G, McMillan-Davey E, Paradis G, Tyndale RF, Clarke P, Hanley J. Source: Tobacco Control. 2002 December; 11(4): 354-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12432161&dopt=Abstract
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Assessment of prenatal smoke exposure by determining nicotine and its metabolites in maternal and neonatal urine. Author(s): Kohler E, Bretschneider D, Rabsilber A, Weise W, Jorch G. Source: Human & Experimental Toxicology. 2001 January; 20(1): 1-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11339618&dopt=Abstract
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Association of the tryptophan hydroxylase gene with smoking initiation but not progression to nicotine dependence. Author(s): Sullivan PF, Jiang Y, Neale MC, Kendler KS, Straub RE. Source: American Journal of Medical Genetics. 2001 July 8; 105(5): 479-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11449402&dopt=Abstract
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Asthma exacerbation after administration of nicotine nasal spray for smoking cessation. Author(s): Roth MT, Westman EC. Source: Pharmacotherapy. 2002 June; 22(6): 779-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12066970&dopt=Abstract
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Attitudes toward nicotine replacement therapy in smokers and ex-smokers in the general public. Author(s): Etter JF, Perneger TV. Source: Clinical Pharmacology and Therapeutics. 2001 March; 69(3): 175-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11240982&dopt=Abstract
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Baseline-dependency of nicotine effects: a review. Author(s): Perkins KA. Source: Behavioural Pharmacology. 1999 November; 10(6-7): 597-615. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10780501&dopt=Abstract
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Basic cardiovascular research and its implications for the medicinal use of nicotine. Author(s): Benowitz NL. Source: Journal of the American College of Cardiology. 2003 February 5; 41(3): 497-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12575982&dopt=Abstract
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Be wary of subsidising nicotine replacement therapy. Author(s): Miller C, Kriven S, Rowley D, Abram L. Source: Tobacco Control. 2002 December; 11(4): 380-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12432167&dopt=Abstract
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Behavior therapy and the transdermal nicotine patch: effects on cessation outcome, affect, and coping. Author(s): Cinciripini PM, Cinciripini LG, Wallfisch A, Haque W, Van Vunakis H. Source: Journal of Consulting and Clinical Psychology. 1996 April; 64(2): 314-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8871416&dopt=Abstract
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Behavioral and cognitive effects of smoking: relationship to nicotine addiction. Author(s): Heishman SJ. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 1999; 1 Suppl 2: S143-7; Discussion S165-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11768172&dopt=Abstract
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Behavioral and neural consequences of prenatal exposure to nicotine. Author(s): Ernst M, Moolchan ET, Robinson ML. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2001 June; 40(6): 630-41. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11392340&dopt=Abstract
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Beneficial effects of nicotine and cigarette smoking: the real, the possible and the spurious. Author(s): Baron JA. Source: British Medical Bulletin. 1996 January; 52(1): 58-73. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8746297&dopt=Abstract
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Binding thermodynamics at the human neuronal nicotine receptor. Author(s): Borea PA, Varani K, Gessi S, Gilli P, Gilli G. Source: Biochemical Pharmacology. 1998 April 15; 55(8): 1189-97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9719473&dopt=Abstract
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Blowing smoke: how cigarette manufacturers argued that nicotine is not addictive. Author(s): Sharfstein J. Source: Tobacco Control. 1999 Summer; 8(2): 210-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10478407&dopt=Abstract
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Brain imaging and the effects of caffeine and nicotine. Author(s): Dager SR, Friedman SD. Source: Annals of Medicine. 2000 December; 32(9): 592-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11209966&dopt=Abstract
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Brain reward system activity in major depression and comorbid nicotine dependence. Author(s): Cardenas L, Tremblay LK, Naranjo CA, Herrmann N, Zack M, Busto UE. Source: The Journal of Pharmacology and Experimental Therapeutics. 2002 September; 302(3): 1265-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12183688&dopt=Abstract
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Brainstem 3H-nicotine receptor binding in the sudden infant death syndrome. Author(s): Nachmanoff DB, Panigrahy A, Filiano JJ, Mandell F, Sleeper LA, ValdesDapena M, Krous HF, White WF, Kinney HC. Source: Journal of Neuropathology and Experimental Neurology. 1998 November; 57(11): 1018-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9825938&dopt=Abstract
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Breaking down boundaries in nicotine and tobacco research. Seventh Annual Meeting Society for Research on Nicotine and Tobacco, Seattle, WA, USA. 23-25 March 2001. Author(s): Wetter D. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2001 August; 3(3): 261-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11506770&dopt=Abstract
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Breastfeeding and the use of recreational drugs--alcohol, caffeine, nicotine and marijuana. Author(s): Liston J. Source: Breastfeed Rev. 1998 August; 6(2): 27-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9849117&dopt=Abstract
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Brief residential treatment for nicotine addiction: a five-year follow-up study. Author(s): Hoffman EH, Blackburn C, Cullari S. Source: Psychological Reports. 2001 August; 89(1): 99-105. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11729559&dopt=Abstract
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Brown adipose tissue. III. Effect of ethanol, nicotine and caffeine exposure. Author(s): Sidlo J, Zaviacic M, Trutzova H. Source: Soud Lek. 1996 May; 41(2): 20-2. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9560910&dopt=Abstract
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Bupropion for the treatment of nicotine dependence in spit tobacco users: a pilot study. Author(s): Dale LC, Ebbert JO, Schroeder DR, Croghan IT, Rasmussen DF, Trautman JA, Cox LS, Hurt RD. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2002 August; 4(3): 267-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12215235&dopt=Abstract
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Bupropion: a new treatment for smokers. Nicotine replacement treatment should also be available on the NHS. Author(s): Britton J, Jarvis MJ. Source: Bmj (Clinical Research Ed.). 2000 July 8; 321(7253): 65-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10884238&dopt=Abstract
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Cannabis: a Trojan horse for nicotine? Author(s): Burns CB, Ivers RG, Lindorff KJ, Clough AR. Source: Aust N Z J Public Health. 2000 December; 24(6): 637. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11215017&dopt=Abstract
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Cardiovascular effects of nasal and transdermal nicotine and cigarette smoking. Author(s): Benowitz NL, Hansson A, Jacob P 3rd. Source: Hypertension. 2002 June; 39(6): 1107-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12052850&dopt=Abstract
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Cardiovascular effects of transdermal nicotine in mildly hypertensive smokers. Author(s): Tanus-Santos JE, Toledo JC, Cittadino M, Sabha M, Rocha JC, Moreno H Jr. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 2001 July; 14(7 Pt 1): 610-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11465642&dopt=Abstract
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Catecholamine and neuropeptide Y secretion from human adrenal chromaffin cells: effect of nicotine and KCl. Author(s): Cavadas C, Ribeiro CA, Cotrim M, Mosimann F, Brunner HR, Grouzmann E. Source: Annals of the New York Academy of Sciences. 2002 October; 971: 332-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12438144&dopt=Abstract
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Cellular and synaptic mechanisms of nicotine addiction. Author(s): Mansvelder HD, McGehee DS. Source: Journal of Neurobiology. 2002 December; 53(4): 606-17. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12436424&dopt=Abstract
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Central role of fibroblast alpha3 nicotinic acetylcholine receptor in mediating cutaneous effects of nicotine. Author(s): Arredondo J, Hall LL, Ndoye A, Nguyen VT, Chernyavsky AI, Bercovich D, Orr-Urtreger A, Beaudet AL, Grando SA. Source: Laboratory Investigation; a Journal of Technical Methods and Pathology. 2003 February; 83(2): 207-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12594236&dopt=Abstract
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Changes in conformation and subcellular distribution of alpha4beta2 nicotinic acetylcholine receptors revealed by chronic nicotine treatment and expression of subunit chimeras. Author(s): Harkness PC, Millar NS. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2002 December 1; 22(23): 10172-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12451118&dopt=Abstract
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Changing places: illicit drugs, medicines, tobacco and nicotine in the nineteenth and twentieth centuries. Author(s): Berridge V. Source: Clio Medica (Amsterdam, Netherlands). 2002; 66: 11-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12028669&dopt=Abstract
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Characterization of nicotine and cotinine N-glucuronidations in human liver microsomes. Author(s): Nakajima M, Tanaka E, Kwon JT, Yokoi T. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2002 December; 30(12): 1484-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12433823&dopt=Abstract
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Chlorination of guanosine and other nucleosides by hypochlorous acid and myeloperoxidase of activated human neutrophils. Catalysis by nicotine and trimethylamine. Author(s): Masuda M, Suzuki T, Friesen MD, Ravanat JL, Cadet J, Pignatelli B, Nishino H, Ohshima H. Source: The Journal of Biological Chemistry. 2001 November 2; 276(44): 40486-96. Epub 2001 August 31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11533049&dopt=Abstract
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Chronic exposure to nicotine upregulates the human (alpha)4((beta)2 nicotinic acetylcholine receptor function. Author(s): Buisson B, Bertrand D. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2001 March 15; 21(6): 1819-29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11245666&dopt=Abstract
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Chronic nicotine treatment reduces beta-amyloidosis in the brain of a mouse model of Alzheimer's disease (APPsw). Author(s): Nordberg A, Hellstrom-Lindahl E, Lee M, Johnson M, Mousavi M, Hall R, Perry E, Bednar I, Court J. Source: Journal of Neurochemistry. 2002 May; 81(3): 655-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12065674&dopt=Abstract
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Chronic tolerance to nicotine in humans and its relationship to tobacco dependence. Author(s): Perkins KA. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2002 November; 4(4): 405-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12521400&dopt=Abstract
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Cigarette-derived nicotine is not a medicine. Author(s): Parrott AC. Source: World J Biol Psychiatry. 2003 April; 4(2): 49-55. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12692774&dopt=Abstract
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Clinical effects of locally delivered nicotine in obstructive sleep apnea syndrome. Author(s): Zevin S, Swed E, Cahan C. Source: American Journal of Therapeutics. 2003 May-June; 10(3): 170-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12756424&dopt=Abstract
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Clinical trial comparing nicotine replacement therapy (NRT) plus brief counselling, brief counselling alone, and minimal intervention on smoking cessation in hospital inpatients. Author(s): Molyneux A, Lewis S, Leivers U, Anderton A, Antoniak M, Brackenridge A, Nilsson F, McNeill A, West R, Moxham J, Britton J. Source: Thorax. 2003 June; 58(6): 484-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12775857&dopt=Abstract
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Cocaine-like subjective effects of nicotine are not blocked by the D1 selective antagonist ecopipam (SCH 39166). Author(s): Chausmer AL, Smith BJ, Kelly RY, Griffiths RR. Source: Behavioural Pharmacology. 2003 March; 14(2): 111-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12658071&dopt=Abstract
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Cognitive avoidance as a method of coping with a provocative smoking cue: the moderating effect of nicotine dependence. Author(s): Shadel WG, Niaura R, Goldstein MG, Abrams DB. Source: Journal of Behavioral Medicine. 2001 April; 24(2): 169-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11392918&dopt=Abstract
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Cognitive effects of nicotine in humans: an fMRI study. Author(s): Kumari V, Gray JA, ffytche DH, Mitterschiffthaler MT, Das M, Zachariah E, Vythelingum GN, Williams SC, Simmons A, Sharma T. Source: Neuroimage. 2003 July; 19(3): 1002-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12880828&dopt=Abstract
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Cognitive effects of nicotine. Author(s): Rezvani AH, Levin ED. Source: Biological Psychiatry. 2001 February 1; 49(3): 258-67. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11230877&dopt=Abstract
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Colonic motility in chronic ulcerative proctosigmoiditis and the effects of nicotine on colonic motility in patients and healthy subjects. Author(s): Coulie B, Camilleri M, Bharucha AE, Sandborn WJ, Burton D. Source: Alimentary Pharmacology & Therapeutics. 2001 May; 15(5): 653-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11328259&dopt=Abstract
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Combination nicotine replacement therapy for smoking cessation: rationale, efficacy and tolerability. Author(s): Sweeney CT, Fant RV, Fagerstrom KO, McGovern JF, Henningfield JE. Source: Cns Drugs. 2001; 15(6): 453-67. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11524024&dopt=Abstract
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Commentary on: "Effects of scopolamine and nicotine on human rapid information processing performance." Psychopharmacology (1984) 82:147-150. Nicotine improves information processing: saying the unthinkable. Author(s): Warburton DM. Source: Psychopharmacology. 2002 August; 162(4): 345-8. Epub 2002 June 27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12172687&dopt=Abstract
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Comparative effects of tobacco smoking and nasal nicotine. Author(s): Teter CJ, Asfaw B, Ni L, Lutz M, Domino EF, Guthrie SK. Source: European Journal of Clinical Pharmacology. 2002 August; 58(5): 309-14. Epub 2002 June 27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12185553&dopt=Abstract
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Comparative efficacy of 24-hour and 16-hour transdermal nicotine patches for relief of morning craving. Author(s): Shiffman S, Elash CA, Paton SM, Gwaltney CJ, Paty JA, Clark DB, Liu KS, Di Marino ME. Source: Addiction (Abingdon, England). 2000 August; 95(8): 1185-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11092066&dopt=Abstract
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Comparison of nicotine patch alone versus nicotine nasal spray alone versus a combination for treating smokers: a minimal intervention, randomized multicenter trial in a nonspecialized setting. Author(s): Croghan GA, Sloan JA, Croghan IT, Novotny P, Hurt RD, DeKrey WL, Mailliard JA, Ebbert LP, Swan DK, Walsh DJ, Wiesenfeld M, Levitt R, Stella P, Johnson PA, Tschetter LK, Loprinzi C. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2003 April; 5(2): 181-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745490&dopt=Abstract
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Comparison of plasma levels of cytokines and in vitro generation of reactive oxygen species after nicotine infusion in nicotine users with normal and impaired renal function. Author(s): Whiss PA, Bengtsson T, Larsson R. Source: Immunopharmacology and Immunotoxicology. 2003 May; 25(2): 131-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12784908&dopt=Abstract
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Comparison of the effects of combined nicotine replacement therapy vs. cigarette smoking in males. Author(s): Haustein KO, Krause J, Haustein H, Rasmussen T, Cort N. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2003 April; 5(2): 195-203. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745492&dopt=Abstract
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Comparison of the nicotine content of tobacco used in bidis and conventional cigarettes. Author(s): Malson JL, Sims K, Murty R, Pickworth WB. Source: Tobacco Control. 2001 June; 10(2): 181-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11387541&dopt=Abstract
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Conference summary Fifth Annual Meeting. Society for Research on Nicotine and Tobacco. San Diego, CA, USA. 5-7 March 1999. Author(s): Schmitz JM. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 1999 September; 1(3): 269-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11072424&dopt=Abstract
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Conflicting evidence for the dopamine release theory of nicotine/tobacco dependence. Author(s): Domino EF. Source: Nihon Shinkei Seishin Yakurigaku Zasshi. 2002 October; 22(5): 181-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12451690&dopt=Abstract
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Contingent monetary reinforcement of smoking reductions, with and without transdermal nicotine, in outpatients with schizophrenia. Author(s): Tidey JW, O'Neill SC, Higgins ST. Source: Experimental and Clinical Psychopharmacology. 2002 August; 10(3): 241-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12233984&dopt=Abstract
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Continued dependence on nicotine replacement therapy should be reported and discussed in smoking cessation trials. Author(s): Gylys J. Source: Archives of Internal Medicine. 2000 July 10; 160(13): 2062-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10888983&dopt=Abstract
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Contribution of nicotine to acute endothelial dysfunction in long-term smokers. Author(s): Neunteufl T, Heher S, Kostner K, Mitulovic G, Lehr S, Khoschsorur G, Schmid RW, Maurer G, Stefenelli T. Source: Journal of the American College of Cardiology. 2002 January 16; 39(2): 251-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11788216&dopt=Abstract
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Controlled trial of three weeks nicotine replacement treatment in hospital patients also given advice and support. Author(s): Hand S, Edwards S, Campbell IA, Cannings R. Source: Thorax. 2002 August; 57(8): 715-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12149533&dopt=Abstract
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Correlation between nicotine-induced inhibition of hematopoiesis and decreased CD44 expression on bone marrow stromal cells. Author(s): Khaldoyanidi S, Sikora L, Orlovskaya I, Matrosova V, Kozlov V, Sriramarao P. Source: Blood. 2001 July 15; 98(2): 303-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11435297&dopt=Abstract
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Could nicotine be beneficial for Behcet's disease? Author(s): Kaklamani VG, Markomichelakis N, Kaklamanis PG. Source: Clinical Rheumatology. 2002 August; 21(4): 341-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12296287&dopt=Abstract
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Cross-desensitization of capsaicin-evoked oral irritation by high but not low concentrations of nicotine in human subjects. Author(s): Dessirier JM, Chang HK, O'Mahony M, Carstens E. Source: Neuroscience Letters. 2000 August 25; 290(2): 133-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10936695&dopt=Abstract
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Current evidence for neuroprotective effects of nicotine and caffeine against Parkinson's disease. Author(s): Ross GW, Petrovitch H. Source: Drugs & Aging. 2001; 18(11): 797-806. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11772120&dopt=Abstract
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Cytisine derivatives as ligands for neuronal nicotine receptors and with various pharmacological activities. Author(s): Boido CC, Tasso B, Boido V, Sparatore F. Source: Farmaco (Societa Chimica Italiana : 1989). 2003 March; 58(3): 265-77. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12620422&dopt=Abstract
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Deficient cotinine formation from nicotine is attributed to the whole deletion of the CYP2A6 gene in humans. Author(s): Nakajima M, Yamagishi S, Yamamoto H, Yamamoto T, Kuroiwa Y, Yokoi T. Source: Clinical Pharmacology and Therapeutics. 2000 January; 67(1): 57-69. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10668854&dopt=Abstract
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Deficient C-oxidation of nicotine continued. Author(s): Benowitz NL, Griffin C, Tyndale R. Source: Clinical Pharmacology and Therapeutics. 2001 December; 70(6): 567. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11753274&dopt=Abstract
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Delirium from nicotine withdrawal in neuro-ICU patients. Author(s): Mayer SA, Chong JY, Ridgway E, Min KC, Commichau C, Bernardini GL. Source: Neurology. 2001 August 14; 57(3): 551-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11502936&dopt=Abstract
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Delivery devices and protecting the next generation from nicotine. Author(s): Barrett J. Source: Molecular Medicine Today. 1995 November; 1(8): 351. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9415179&dopt=Abstract
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Depression and self-medication with nicotine: the modifying influence of the dopamine D4 receptor gene. Author(s): Lerman C, Caporaso N, Main D, Audrain J, Boyd NR, Bowman ED, Shields PG. Source: Health Psychology : Official Journal of the Division of Health Psychology, American Psychological Association. 1998 January; 17(1): 56-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9459071&dopt=Abstract
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Depressive symptoms and smoking cessation among inner-city African Americans using the nicotine patch. Author(s): Catley D, Ahluwalia JS, Resnicow K, Nazir N. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2003 February; 5(1): 61-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745507&dopt=Abstract
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Deprivation state but not nicotine content of the cigarette affects responding by smokers on a progressive ratio task. Author(s): Rusted JM, Mackee A, Williams R, Willner P. Source: Psychopharmacology. 1998 December; 140(4): 411-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9888615&dopt=Abstract
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Determinants of plasma concentrations of nicotine and cotinine during cigarette smoking and transdermal nicotine treatment. Author(s): Gourlay SG, Benowitz NL, Forbes A, McNeil JJ. Source: European Journal of Clinical Pharmacology. 1997; 51(5): 407-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9049583&dopt=Abstract
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Determination of nicotine as an indicator of environmental tobacco smoke in restaurants. Author(s): Kuusimaki L, Pfaffli P, Froshaug M, Becher G, Dybing E, Peltonen K. Source: American Journal of Industrial Medicine. 1999 September; Suppl 1: 152-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10519819&dopt=Abstract
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Determination of nicotine in water by gradient ion chromatography. Author(s): Ayers GP, Selleck PW, Gillett RW, Keywood MD. Source: J Chromatogr A. 1998 October 23; 824(2): 241-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9818435&dopt=Abstract
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Determination of the nicotine content of various edible nightshades (Solanaceae) and their products and estimation of the associated dietary nicotine intake. Author(s): Siegmund B, Leitner E, Pfannhauser W. Source: Journal of Agricultural and Food Chemistry. 1999 August; 47(8): 3113-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10552617&dopt=Abstract
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Development and evaluation of a biphasic buccal adhesive tablet for nicotine replacement therapy. Author(s): Park CR, Munday DL. Source: International Journal of Pharmaceutics. 2002 April 26; 237(1-2): 215-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11955819&dopt=Abstract
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Development of a rectal nicotine delivery system for the treatment of ulcerative colitis. Author(s): Dash AK, Gong Z, Miller DW, Huai-Yan H, Laforet J. Source: International Journal of Pharmaceutics. 1999 November 10; 190(1): 21-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10528093&dopt=Abstract
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Development of a screening questionnaire for tobacco/nicotine dependence according to ICD-10, DSM-III-R, and DSM-IV. Author(s): Kawakami N, Takatsuka N, Inaba S, Shimizu H. Source: Addictive Behaviors. 1999 March-April; 24(2): 155-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10336098&dopt=Abstract
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Development of a versatile method for the detection of nicotine in air. Author(s): Pendergrass SM, Krake AM, Jaycox LB. Source: Aihaj : a Journal for the Science of Occupational and Environmental Health and Safety. 2000 July-August; 61(4): 469-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10976675&dopt=Abstract
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Developmental cholinotoxicants: nicotine and chlorpyrifos. Author(s): Slotkin TA. Source: Environmental Health Perspectives. 1999 February; 107 Suppl 1: 71-80. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10229709&dopt=Abstract
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Diagnosis and treatment of nicotine dependence with emphasis on nicotine replacement therapy. A status report. Author(s): Balfour D, Benowitz N, Fagerstrom K, Kunze M, Keil U. Source: European Heart Journal. 2000 March; 21(6): 438-45. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10681484&dopt=Abstract
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Differential effects of transdermal nicotine on microstructured analyses of tics in Tourette's syndrome: an open study. Author(s): Dursun SM, Reveley MA. Source: Psychological Medicine. 1997 March; 27(2): 483-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9089841&dopt=Abstract
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Direct and indirect effects of nicotine/smoking on cognition in humans. Author(s): Waters AJ, Sutton SR. Source: Addictive Behaviors. 2000 January-February; 25(1): 29-43. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10708317&dopt=Abstract
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Direct block of inward rectifier potassium channels by nicotine. Author(s): Wang H, Yang B, Zhang L, Xu D, Wang Z. Source: Toxicology and Applied Pharmacology. 2000 April 1; 164(1): 97-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10739749&dopt=Abstract
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Discriminative stimulus properties of nicotine at low doses: the effects of caffeine preload. Author(s): Duka T, Tasker R, Russell K, Stephens DN. Source: Behavioural Pharmacology. 1998 May; 9(3): 219-29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9832936&dopt=Abstract
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Dissociating nicotine and nonnicotine components of cigarette smoking. Author(s): Rose JE, Behm FM, Westman EC, Johnson M. Source: Pharmacology, Biochemistry, and Behavior. 2000 September; 67(1): 71-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11113486&dopt=Abstract
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Dissociation of nicotine tolerance from tobacco dependence in humans. Author(s): Perkins KA, Gerlach D, Broge M, Grobe JE, Sanders M, Fonte C, Vender J, Cherry C, Wilson A. Source: The Journal of Pharmacology and Experimental Therapeutics. 2001 March; 296(3): 849-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11181916&dopt=Abstract
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Distal ulcerative colitis refractory to rectal mesalamine: role of transdermal nicotine versus oral mesalamine. Author(s): Guslandi M, Frego R, Viale E, Testoni PA. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2002 May; 16(5): 293-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12045777&dopt=Abstract
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Diversity of selective environmental substrates for human cytochrome P450 2A6: alkoxyethers, nicotine, coumarin, N-nitrosodiethylamine, and Nnitrosobenzylmethylamine. Author(s): Le Gal A, Dreano Y, Lucas D, Berthou F. Source: Toxicology Letters. 2003 September 15; 144(1): 77-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12919726&dopt=Abstract
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Do adolescent smokers experience withdrawal effects when deprived of nicotine? Author(s): Killen JD, Ammerman S, Rojas N, Varady J, Haydel F, Robinson TN. Source: Experimental and Clinical Psychopharmacology. 2001 May; 9(2): 176-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11518093&dopt=Abstract
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Do former smokers respond to nicotine differently from never smokers? A pilot study. Author(s): Hughes JR, Rose GL, Callas PW. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2000 August; 2(3): 255-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11082826&dopt=Abstract
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Do heavy smokers benefit from higher dose nicotine patch therapy? Author(s): Killen JD, Fortmann SP, Davis L, Strausberg L, Varady A. Source: Experimental and Clinical Psychopharmacology. 1999 August; 7(3): 226-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10472510&dopt=Abstract
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Do the origins of behavior matter? Commentary on Perkins' Baseline-dependency of nicotine effects: a review. Author(s): Branch MN. Source: Behavioural Pharmacology. 1999 November; 10(6-7): 617-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10780502&dopt=Abstract
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Doctors told to treat nicotine addiction as a disease. Author(s): Kmietowicz Z. Source: Bmj (Clinical Research Ed.). 2000 February 12; 320(7232): 397. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10669428&dopt=Abstract
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Does a reduced sensitivity to bitter taste increase the risk of becoming nicotine addicted? Author(s): Enoch MA, Harris CR, Goldman D. Source: Addictive Behaviors. 2001 May-June; 26(3): 399-404. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11436931&dopt=Abstract
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Does abstinence from smoking or a transdermal nicotine system influence atracurium-induced neuromuscular block? Author(s): Puura AI, Rorarius MG, Laippala P, Baer GA. Source: Anesthesia and Analgesia. 1998 August; 87(2): 430-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9706945&dopt=Abstract
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Does noise stress modulate effects of smoking/nicotine? Mood, vigilance, and EEG responses. Author(s): Gilbert DG, Estes SL, Welser R. Source: Psychopharmacology. 1997 February; 129(4): 382-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9085408&dopt=Abstract
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Dopamine agonist and antagonist responders as related to types of nicotine craving and facets of extraversion. Author(s): Reuter M, Netter P, Toll C, Hennig J. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2002 June; 26(5): 845-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12369256&dopt=Abstract
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Dose-dependent stereoselective activation of the trigeminal sensory system by nicotine in man. Author(s): Thuerauf N, Kaegler M, Dietz R, Barocka A, Kobal G. Source: Psychopharmacology. 1999 March; 142(3): 236-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10208315&dopt=Abstract
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Dose-related cardiovascular and endocrine effects of transdermal nicotine. Author(s): Zevin S, Jacob P 3rd, Benowitz NL. Source: Clinical Pharmacology and Therapeutics. 1998 July; 64(1): 87-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9695723&dopt=Abstract
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Doses of nicotine and lung carcinogens delivered to cigarette smokers. Author(s): Djordjevic MV, Stellman SD, Zang E. Source: Journal of the National Cancer Institute. 2000 January 19; 92(2): 106-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10639511&dopt=Abstract
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Double-blind placebo controlled trial of dextrose tablets and nicotine patch in smoking cessation. Author(s): West R, Willis N. Source: Psychopharmacology. 1998 March; 136(2): 201-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9551778&dopt=Abstract
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Drug may suppress the craving for nicotine. Author(s): Wickelgren I. Source: Science. 1998 December 4; 282(5395): 1797,1799. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9874627&dopt=Abstract
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Dynamic behavior of semivolatile organic compounds in indoor air. 2. Nicotine and phenanthrene with carpet and wallboard. Author(s): Van Loy MD, Riley WJ, Daisey JM, Nazaroff WW. Source: Environmental Science & Technology. 2001 February 1; 35(3): 560-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11351729&dopt=Abstract
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Early emotional disturbances during nicotine patch therapy in subjects with and without a history of depression. Author(s): Carton S, Le Houezec J, Lagrue G, Jouvent R. Source: Journal of Affective Disorders. 2002 November; 72(2): 195-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12200210&dopt=Abstract
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Effect of chewing gum containing nicotine and caffeine on energy expenditure and substrate utilization in men. Author(s): Jessen AB, Toubro S, Astrup A. Source: The American Journal of Clinical Nutrition. 2003 June; 77(6): 1442-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12791621&dopt=Abstract
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Effect of nicotine and nicotinic receptors on anxiety and depression. Author(s): Picciotto MR, Brunzell DH, Caldarone BJ. Source: Neuroreport. 2002 July 2; 13(9): 1097-106. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12151749&dopt=Abstract
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Effect of nicotine on inflammatory bowel disease. Author(s): Naser SA, Ghobrial G, Miles H. Source: The American Journal of Gastroenterology. 2001 December; 96(12): 3455-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11774981&dopt=Abstract
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Effect of nicotine on vasoconstrictor and vasodilator responses in human skin vasculature. Author(s): Black CE, Huang N, Neligan PC, Levine RH, Lipa JE, Lintlop S, Forrest CR, Pang CY. Source: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 2001 October; 281(4): R1097-104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11557615&dopt=Abstract
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Effect of nicotine replacement and quitting smoking on circulating adhesion molecule profiles (sICAM-1, sCD44v5, sCD44v6). Author(s): Palmer RM, Stapleton JA, Sutherland G, Coward PY, Wilson RF, Scott DA. Source: European Journal of Clinical Investigation. 2002 November; 32(11): 852-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12423327&dopt=Abstract
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Effect of nicotine-treated epithelial cells on the proliferation and collagen production of gingival fibroblasts. Author(s): Giannopoulou C, Roehrich N, Mombelli A. Source: Journal of Clinical Periodontology. 2001 August; 28(8): 769-75. English, French, German. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11442737&dopt=Abstract
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Effect of smoking and transdermal nicotine on colonic nicotinic acetylcholine receptors in ulcerative colitis. Author(s): Richardson CE, Morgan JM, Jasani B, Green JT, Rhodes J, Williams GT, Lindstrom J, Wonnacott S, Peel S, Thomas GA. Source: Qjm : Monthly Journal of the Association of Physicians. 2003 January; 96(1): 5765. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12509650&dopt=Abstract
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Effectiveness of over-the-counter nicotine replacement therapy. Author(s): Franzon M, Gustavsson G, Korberly BH. Source: Jama : the Journal of the American Medical Association. 2002 December 25; 288(24): 3108; Author Reply 3110. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12495386&dopt=Abstract
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Effectiveness of over-the-counter nicotine replacement therapy. Author(s): Antonuccio DO. Source: Jama : the Journal of the American Medical Association. 2002 December 25; 288(24): 3108; Author Reply 3110. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12495385&dopt=Abstract
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Effectiveness of over-the-counter nicotine replacement therapy. Author(s): Stead LF, Davis RM, Fiore MC, Hatsukami DK, Raw M, West R. Source: Jama : the Journal of the American Medical Association. 2002 December 25; 288(24): 3109-10; Author Reply 3110. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12495384&dopt=Abstract
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Effectiveness of over-the-counter nicotine replacement therapy. Author(s): Cadore JM. Source: Jama : the Journal of the American Medical Association. 2002 December 25; 288(24): 3108-9; Author Reply 3110. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12495383&dopt=Abstract
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Effects of a low dose of transdermal nicotine on information processing. Author(s): Davranche K, Audiffren M. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2002 August; 4(3): 275-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12215236&dopt=Abstract
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Effects of a single transdermal nicotine dose on cognitive performance in adults with Down syndrome. Author(s): Bernert G, Sustrova M, Sovcikova E, Seidl R, Lubec G. Source: Journal of Neural Transmission. Supplementum. 2001; (61): 237-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11771747&dopt=Abstract
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Effects of acute nicotine administration on cognitive event-related potentials in tacrine-treated and non-treated patients with Alzheimer's disease. Author(s): Knott V, Mohr E, Mahoney C, Engeland C, Ilivitsky V. Source: Neuropsychobiology. 2002; 45(3): 156-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11979067&dopt=Abstract
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Effects of alkaline phosphatase and its inhibitor levamisole on the modulation of androgen metabolism by nicotine and minocycline in human gingival and oral periosteal fibroblasts. Author(s): Soory M, Suchak A. Source: Archives of Oral Biology. 2003 January; 48(1): 69-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12615144&dopt=Abstract
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Effects of chronic nicotine and methylphenidate in adults with attention deficit/hyperactivity disorder. Author(s): Levin ED, Conners CK, Silva D, Canu W, March J. Source: Experimental and Clinical Psychopharmacology. 2001 February; 9(1): 83-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11519638&dopt=Abstract
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Effects of cigarette smoking and nicotine nasal spray on psychiatric symptoms and cognition in schizophrenia. Author(s): Smith RC, Singh A, Infante M, Khandat A, Kloos A. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2002 September; 27(3): 479-97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12225705&dopt=Abstract
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Effects of cigarette smoking or nicotine replacement on cardiovascular risk factors and parameters of haemorheology. Author(s): Haustein KO, Krause J, Haustein H, Rasmussen T, Cort N. Source: Journal of Internal Medicine. 2002 August; 252(2): 130-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12190888&dopt=Abstract
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Effects of nicotine chewing gum on UPDRS score and P300 in early-onset parkinsonism. Author(s): Mitsuoka T, Kaseda Y, Yamashita H, Kohriyama T, Kawakami H, Nakamura S, Yamamura Y. Source: Hiroshima J Med Sci. 2002 March; 51(1): 33-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11999458&dopt=Abstract
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Effects of nicotine deprivation and irritability on physical aggression in male smokers. Author(s): Parrott DJ, Zeichner A. Source: Psychology of Addictive Behaviors : Journal of the Society of Psychologists in Addictive Behaviors. 2001 June; 15(2): 133-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11419229&dopt=Abstract
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Effects of nicotine deprivation on craving response covariation in smokers. Author(s): Sayette MA, Martin CS, Hull JG, Wertz JM, Perrott MA. Source: Journal of Abnormal Psychology. 2003 February; 112(1): 110-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12653419&dopt=Abstract
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Effects of nicotine deprivation on urges to drink and smoke in alcoholic smokers. Author(s): Cooney JL, Cooney NL, Pilkey DT, Kranzler HR, Oncken CA. Source: Addiction (Abingdon, England). 2003 July; 98(7): 913-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12814497&dopt=Abstract
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Effects of nicotine on alcohol consumption. Author(s): Le AD. Source: Alcoholism, Clinical and Experimental Research. 2002 December; 26(12): 1915-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12500118&dopt=Abstract
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Effects of sex hormones, forskolin, and nicotine on choline acetyltransferase activity in human isolated placenta. Author(s): Wessler I, Schwarze S, Brockerhoff P, Bittinger F, Kirkpatrick CJ, Kilbinger H. Source: Neurochemical Research. 2003 April; 28(3-4): 489-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12675136&dopt=Abstract
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Effects of smoking/nicotine on performance and event-related potentials during a short-term memory scanning task. Author(s): Houlihan ME, Pritchard WS, Robinson JH. Source: Psychopharmacology. 2001 August; 156(4): 388-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11498715&dopt=Abstract
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Effects of the nicotine patch on performance during the first week of smoking cessation. Author(s): Cook MR, Gerkovich MM, Graham C, Hoffman SJ, Peterson RC. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2003 April; 5(2): 169-80. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745489&dopt=Abstract
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Effects of transdermal nicotine on learning, memory, verbal fluency, concentration, and general health in a healthy sample at risk for dementia. Author(s): Howe MN, Price IR. Source: Int Psychogeriatr. 2001 December; 13(4): 465-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12003253&dopt=Abstract
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Effects of whole deletion of CYP2A6 on nicotine metabolism in humans. Author(s): Zhang X, Ameno K, Ameno S, Kinoshita H, Kubota T, Kumihashi M, Mostofa J, Iwahashi K, Ijiri I. Source: Drug and Chemical Toxicology. 2002 May; 25(2): 203-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12024803&dopt=Abstract
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Efficacy of a nicotine lozenge for smoking cessation. Author(s): Shiffman S, Dresler CM, Hajek P, Gilburt SJ, Targett DA, Strahs KR. Source: Archives of Internal Medicine. 2002 June 10; 162(11): 1267-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12038945&dopt=Abstract
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Efficacy of acute administration of nicotine gum in relief of cue-provoked cigarette craving. Author(s): Shiffman S, Shadel WG, Niaura R, Khayrallah MA, Jorenby DE, Ryan CF, Ferguson CL. Source: Psychopharmacology. 2003 April; 166(4): 343-50. Epub 2003 February 25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12601502&dopt=Abstract
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Efficacy of nicotine patch in smokers with a history of alcoholism. Author(s): Hughes JR, Novy P, Hatsukami DK, Jensen J, Callas PW. Source: Alcoholism, Clinical and Experimental Research. 2003 June; 27(6): 946-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12824815&dopt=Abstract
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Efficacy of oral transmucosal nicotine lozenge for suppression of withdrawal symptoms in smoking abstinence. Author(s): Muramoto ML, Ranger-Moore J, Leischow SJ. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2003 April; 5(2): 223-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745495&dopt=Abstract
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Efficacy of over-the-counter nicotine patch. Author(s): Shiffman S, Gorsline J, Gorodetzky CW. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2002 November; 4(4): 477-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12521407&dopt=Abstract
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Elucidating the role of genetic factors in smoking behavior and nicotine dependence. Author(s): Lerman C, Berrettini W. Source: American Journal of Medical Genetics. 2003 April 1; 118B(1): 48-54. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12627466&dopt=Abstract
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Enhanced Escherichia coli invasion of human brain microvascular endothelial cells is associated with alternations in cytoskeleton induced by nicotine. Author(s): Chen YH, Chen SH, Jong A, Zhou ZY, Li W, Suzuki K, Huang SH. Source: Cellular Microbiology. 2002 August; 4(8): 503-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12174085&dopt=Abstract
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Ethanol and nicotine: a pharmacologic balancing act? Author(s): Prendergast MA, Rogers DT, Barron S, Bardo MT, Littleton JM. Source: Alcoholism, Clinical and Experimental Research. 2002 December; 26(12): 1917-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12500119&dopt=Abstract
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Evaluation of subclinical respiratory tract inflammation in heavy smokers who switch to a cigarette-like nicotine delivery device that primarily heats tobacco. Author(s): Rennard SI, Umino T, Millatmal T, Daughton DM, Manouilova LS, Ullrich FA, Patil KD, Romberger DJ, Floreani AA, Anderson JR. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2002 November; 4(4): 467-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12521406&dopt=Abstract
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Evidence for the immunosuppressive role of nicotine on human dendritic cell functions. Author(s): Nouri-Shirazi M, Guinet E. Source: Immunology. 2003 July; 109(3): 365-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12807482&dopt=Abstract
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Evidence that transient nicotine lowers the body weight set point. Author(s): Cabanac M, Frankham P. Source: Physiology & Behavior. 2002 August; 76(4-5): 539-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12126990&dopt=Abstract
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Failure to reduce nicotine addiction in young adults with diabetes. Author(s): Ismail AA, Wallymahmed ME, Gill GV, MacFarlane IA. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 2000 April; 17(4): 330-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10821303&dopt=Abstract
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FDA and EPA setbacks, fetal nicotine, ASH Thailand and UK, tennis shame, Australian documents, Corporate Activity Project, and 2100 quotes. Author(s): Cannon J. Source: Tobacco Control. 1998 Autumn; 7(3): 320-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9825427&dopt=Abstract
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Fetal growth and length of gestation in relation to prenatal exposure to environmental tobacco smoke assessed by hair nicotine concentration. Author(s): Jaakkola JJ, Jaakkola N, Zahlsen K. Source: Environmental Health Perspectives. 2001 June; 109(6): 557-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11445507&dopt=Abstract
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Fetal nicotine or cocaine exposure: which one is worse? Author(s): Slotkin TA. Source: The Journal of Pharmacology and Experimental Therapeutics. 1998 June; 285(3): 931-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9618392&dopt=Abstract
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Filter ventilation and nicotine content of tobacco in cigarettes from Canada, the United Kingdom, and the United States. Author(s): Kozlowski LT, Mehta NY, Sweeney CT, Schwartz SS, Vogler GP, Jarvis MJ, West RJ. Source: Tobacco Control. 1998 Winter; 7(4): 369-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10093170&dopt=Abstract
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First and second transmembrane segments of alpha3, alpha4, beta2, and beta4 nicotinic acetylcholine receptor subunits influence the efficacy and potency of nicotine. Author(s): Rush R, Kuryatov A, Nelson ME, Lindstrom J. Source: Molecular Pharmacology. 2002 June; 61(6): 1416-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12021403&dopt=Abstract
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First experiences of prescribing nicotine replacement therapy as part of a smoking cessation service on an SSBN patrol. Author(s): Martin N. Source: J R Nav Med Serv. 2002; 88(2): 57-60. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12500484&dopt=Abstract
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Flavor improvement does not increase abuse liability of nicotine chewing gum. Author(s): Houtsmuller EJ, Fant RV, Eissenberg TE, Henningfield JE, Stitzer ML. Source: Pharmacology, Biochemistry, and Behavior. 2002 June; 72(3): 559-68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12175452&dopt=Abstract
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Flow injection Fourier transform infrared determination of nicotine in tobacco. Author(s): Garrigues JM, Perez-Ponce A, Garrigues S, de la Guardia M. Source: The Analyst. 1999 May; 124(5): 783-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10616740&dopt=Abstract
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Focus groups with pregnant smokers: barriers to cessation, attitudes to nicotine patch use and perceptions of cessation counselling by care providers. Author(s): Hotham ED, Atkinson ER, Gilbert AL. Source: Drug and Alcohol Review. 2002 June; 21(2): 163-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12188995&dopt=Abstract
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Formation and retention of cotinine during placental transfer of nicotine in human placental cotyledon. Author(s): Sastry BV, Chance MB, Hemontolor ME, Goddijn-Wessel TA. Source: Pharmacology. 1998 August; 57(2): 104-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9691230&dopt=Abstract
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Formation of the quaternary ammonium-linked glucuronide of nicotine in human liver microsomes: identification and stereoselectivity in the kinetics. Author(s): Ghosheh O, Vashishtha SC, Hawes EM. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2001 December; 29(12): 1525-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11717169&dopt=Abstract
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Forum. Which aspects of nicotine addiction should concern mental health professionials? Author(s): Glassman AH, Hercher LS. Source: The Harvard Mental Health Letter / from Harvard Medical School. 1999 August; 16(2): 8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10402317&dopt=Abstract
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Four-week nicotine skin patch treatment effects on cognitive performance in Alzheimer's disease. Author(s): White HK, Levin ED. Source: Psychopharmacology. 1999 April; 143(2): 158-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10326778&dopt=Abstract
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Framing the nicotine debate: a cultural approach to risk. Author(s): Murphy P. Source: Health Communication. 2001; 13(2): 119-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11451101&dopt=Abstract
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Free nicotine patches plus proactive telephone peer support to help low-income women stop smoking. Author(s): Solomon LJ, Scharoun GM, Flynn BS, Secker-Walker RH, Sepinwall D. Source: Preventive Medicine. 2000 July; 31(1): 68-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10896845&dopt=Abstract
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Functional and developmental studies of the peripheral arterial chemoreceptors in rat: effects of nicotine and possible relation to sudden infant death syndrome. Author(s): Holgert H, Hokfelt T, Hertzberg T, Lagercrantz H. Source: Proceedings of the National Academy of Sciences of the United States of America. 1995 August 1; 92(16): 7575-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7638233&dopt=Abstract
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Functional deactivation of the major neuronal nicotinic receptor caused by nicotine and a protein kinase C-dependent mechanism. Author(s): Eilers H, Schaeffer E, Bickler PE, Forsayeth JR. Source: Molecular Pharmacology. 1997 December; 52(6): 1105-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9415721&dopt=Abstract
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Gabapentin for misuse of homemade nicotine nasal spray. Author(s): Myrick H, Malcolm R, Henderson S, McCormick K. Source: The American Journal of Psychiatry. 2001 March; 158(3): 498. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11230002&dopt=Abstract
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Gender differences in predictors for long-term smoking cessation following physician advice and nicotine replacement therapy. Author(s): D'Angelo ME, Reid RD, Brown KS, Pipe AL. Source: Canadian Journal of Public Health. Revue Canadienne De Sante Publique. 2001 November-December; 92(6): 418-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11799544&dopt=Abstract
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Gender differences in quit rates following smoking cessation with combination nicotine therapy: influence of baseline smoking behavior. Author(s): Bohadana A, Nilsson F, Rasmussen T, Martinet Y. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2003 February; 5(1): 111-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745512&dopt=Abstract
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Gender differences in response to nicotine replacement therapy: objective and subjective indexes of tobacco withdrawal. Author(s): Wetter DW, Fiore MC, Young TB, McClure JB, de Moor CA, Baker TB. Source: Experimental and Clinical Psychopharmacology. 1999 May; 7(2): 135-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10340153&dopt=Abstract
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Gender differences in tobacco smoking: higher relative exposure to smoke than nicotine in women. Author(s): Zeman MV, Hiraki L, Sellers EM. Source: Journal of Women's Health & Gender-Based Medicine. 2002 March; 11(2): 14753. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11975862&dopt=Abstract
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Genetic influences on smoking behavior and nicotine dependence: a review. Author(s): Yoshimasu K, Kiyohara C. Source: J Epidemiol. 2003 July; 13(4): 183-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12934961&dopt=Abstract
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Genetic polymorphisms in human CYP2A6 gene causing impaired nicotine metabolism. Author(s): Yoshida R, Nakajima M, Watanabe Y, Kwon JT, Yokoi T. Source: British Journal of Clinical Pharmacology. 2002 November; 54(5): 511-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12445030&dopt=Abstract
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Genetic polymorphisms in the cytochrome P450 2A6 (CYP2A6) gene: implications for interindividual differences in nicotine metabolism. Author(s): Oscarson M. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2001 February; 29(2): 91-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11159795&dopt=Abstract
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Genetic variation in CYP2A6-mediated nicotine metabolism alters smoking behavior. Author(s): Tyndale RF, Sellers EM. Source: Therapeutic Drug Monitoring. 2002 February; 24(1): 163-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11805739&dopt=Abstract
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Genetic, environmental, and situational factors mediating the effects of nicotine--an introduction. Author(s): Overstreet DH, Karan L, Rosecrans JA. Source: Behavior Genetics. 1995 March; 25(2): 93-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7733861&dopt=Abstract
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Genotyping of human cytochrome P450 2A6 (CYP2A6), a nicotine C-oxidase. Author(s): Oscarson M, Gullsten H, Rautio A, Bernal ML, Sinues B, Dahl ML, Stengard JH, Pelkonen O, Raunio H, Ingelman-Sundberg M. Source: Febs Letters. 1998 November 6; 438(3): 201-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9827545&dopt=Abstract
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Glycation of the amyloid beta-protein by a nicotine metabolite: a fortuitous chemical dynamic between smoking and Alzheimer's disease. Author(s): Dickerson TJ, Janda KD. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 July 8; 100(14): 8182-7. Epub 2003 June 18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12815102&dopt=Abstract
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Greater sensitivity to subjective effects of nicotine in nonsmokers high in sensation seeking. Author(s): Perkins KA, Gerlach D, Broge M, Grobe JE, Wilson A. Source: Experimental and Clinical Psychopharmacology. 2000 November; 8(4): 462-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11127418&dopt=Abstract
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Green tobacco sickness: occupational nicotine poisoning in tobacco workers. Author(s): Ballard T, Ehlers J, Freund E, Auslander M, Brandt V, Halperin W. Source: Archives of Environmental Health. 1995 September-October; 50(5): 384-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7574894&dopt=Abstract
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Growth factor-mediated mechanisms of nicotine-dependent carcinogenesis. Author(s): Rakowicz-Szulczynska EM, McIntosh DG, Smith M. Source: Carcinogenesis. 1994 September; 15(9): 1839-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7923576&dopt=Abstract
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Guide to nicotine replacement therapies. Breath of fresh air. Author(s): Bryan J. Source: Health Serv J. 2001 May 10; 111(5754): Suppl 34-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11383346&dopt=Abstract
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Hair analysis for nicotine and cotinine: evaluation of extraction procedures, hair treatments, and development of reference material. Author(s): Pichini S, Altieri I, Pellegrini M, Pacifici R, Zuccaro P. Source: Forensic Science International. 1997 January 17; 84(1-3): 243-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9042730&dopt=Abstract
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Hair nicotine concentrations in mothers and children in relation to parental smoking. Author(s): Nafstad P, Jaakkola JJ, Hagen JA, Zahlsen K, Magnus P. Source: Journal of Exposure Analysis and Environmental Epidemiology. 1997 AprilJune; 7(2): 235-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9185014&dopt=Abstract
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Haloperidol reduces smoking of both nicotine-containing and denicotinized cigarettes. Author(s): Brauer LH, Cramblett MJ, Paxton DA, Rose JE. Source: Psychopharmacology. 2001 December; 159(1): 31-7. Epub 2001 September 04. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11797066&dopt=Abstract
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Haplotypes of four novel single nucleotide polymorphisms in the nicotinic acetylcholine receptor beta2-subunit (CHRNB2) gene show no association with smoking initiation or nicotine dependence. Author(s): Silverman MA, Neale MC, Sullivan PF, Harris-Kerr C, Wormley B, Sadek H, Ma Y, Kendler KS, Straub RE. Source: American Journal of Medical Genetics. 2000 October 9; 96(5): 646-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11054772&dopt=Abstract
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Heart attacks, smoking, and the nicotine patch. Author(s): Kafka HP. Source: Annals of Internal Medicine. 1994 September 1; 121(5): 389. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8042844&dopt=Abstract
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Helping older adults become nicotine free. Author(s): Miller CA. Source: Geriatric Nursing (New York, N.Y.). 1996 March-April; 17(2): 96-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8707160&dopt=Abstract
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Hiccups following nicotine gum use. Author(s): Einarson TR, Einarson A. Source: The Annals of Pharmacotherapy. 1997 October; 31(10): 1263-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9337460&dopt=Abstract
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High dose transdermal nicotine therapy for heavy smokers: safety, tolerability and measurement of nicotine and cotinine levels. Author(s): Fredrickson PA, Hurt RD, Lee GM, Wingender L, Croghan IT, Lauger G, Gomez-Dahl L, Offord KP. Source: Psychopharmacology. 1995 December; 122(3): 215-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8748390&dopt=Abstract
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High levels of transdermal nicotine exposure produce green tobacco sickness in Latino farmworkers. Author(s): Arcury TA, Quandt SA, Preisser JS, Bernert JT, Norton D, Wang J. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2003 June; 5(3): 315-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12791526&dopt=Abstract
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High-dose nicotine patch therapy. Percentage of replacement and smoking cessation. Author(s): Dale LC, Hurt RD, Offord KP, Lawson GM, Croghan IT, Schroeder DR. Source: Jama : the Journal of the American Medical Association. 1995 November 1; 274(17): 1353-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7563559&dopt=Abstract
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Higher dosage nicotine patches increase one-year smoking cessation rates: results from the European CEASE trial. Collaborative European Anti-Smoking Evaluation. European Respiratory Society. Author(s): Tonnesen P, Paoletti P, Gustavsson G, Russell MA, Saracci R, Gulsvik A, Rijcken B, Sawe U. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 1999 February; 13(2): 238-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10065662&dopt=Abstract
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High-performance liquid chromatographic assay for N-glucuronidation of nicotine and cotinine in human liver microsomes. Author(s): Nakajima M, Kwon JT, Tanaka E, Yokoi T. Source: Analytical Biochemistry. 2002 March 1; 302(1): 131-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11846386&dopt=Abstract
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Histories of harm reduction: illicit drugs, tobacco, and nicotine. Author(s): Berridge V. Source: Substance Use & Misuse. 1999 January; 34(1): 35-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10052389&dopt=Abstract
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Hits and misses in nicotine psychopharmacology: a personal view of research over a period of 30 years. Author(s): Stolerman I. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2002 November; 4(4): 389-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12528675&dopt=Abstract
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Hospitals vs merchants of nicotine. Author(s): Soffer A. Source: Chest. 2002 August; 122(2): 391-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12171802&dopt=Abstract
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How much does relapse after one year erode effectiveness of smoking cessation treatments? Long-term follow up of randomised trial of nicotine nasal spray. Author(s): Stapleton JA, Sutherland G, Russell MA. Source: Bmj (Clinical Research Ed.). 1998 March 14; 316(7134): 830-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9565457&dopt=Abstract
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Hubble-bubble (water pipe) smoking: levels of nicotine and cotinine in plasma, saliva and urine. Author(s): Shafagoj YA, Mohammed FI, Hadidi KA. Source: Int J Clin Pharmacol Ther. 2002 June; 40(6): 249-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12078938&dopt=Abstract
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Identification and characterisation of novel polymorphisms in the CYP2A locus: implications for nicotine metabolism. Author(s): Oscarson M, McLellan RA, Gullsten H, Agundez JA, Benitez J, Rautio A, Raunio H, Pelkonen O, Ingelman-Sundberg M. Source: Febs Letters. 1999 October 29; 460(2): 321-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10544257&dopt=Abstract
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Imaging the neurochemistry of nicotine actions: studies with positron emission tomography. Author(s): Volkow ND, Fowler JS, Ding YS, Wang GJ, Gatley SJ. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 1999; 1 Suppl 2: S127-32; Discussion S139-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11768169&dopt=Abstract
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Impact of intravenous nicotine on BOLD signal response to photic stimulation. Author(s): Jacobsen LK, Gore JC, Skudlarski P, Lacadie CM, Jatlow P, Krystal JH. Source: Magnetic Resonance Imaging. 2002 February; 20(2): 141-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12034334&dopt=Abstract
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Impact of messages on concomitant use of nicotine replacement therapy and cigarettes: a randomized trial on the Internet. Author(s): Etter JF, le Houezec J, Landfeldt B. Source: Addiction (Abingdon, England). 2003 July; 98(7): 941-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12814500&dopt=Abstract
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Impact of prior nicotine replacement therapy on smoking cessation efficacy. Author(s): Durcan MJ, White J, Jorenby DE, Fiore MC, Rennard SI, Leischow SJ, Nides MA, Ascher JA, Johnston JA. Source: American Journal of Health Behavior. 2002 May-June; 26(3): 213-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12018757&dopt=Abstract
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Implications for tobacco regulation and public health. Commentary on Stolerman's Inter-species consistency in the behavioural pharmacology of nicotine dependence. Author(s): Henningfield JE. Source: Behavioural Pharmacology. 1999 November; 10(6-7): 581-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10780498&dopt=Abstract
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Implications of nicotine dependence: need for revision of tobacco product regulations. Author(s): Ramstrom LM. Source: Wiener Klinische Wochenschrift. 2003 June 24; 115(11): 401-2; Author Reply 402. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12879739&dopt=Abstract
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Implications of the autonomy theory of nicotine dependence. Author(s): DiFranza JR. Source: Medgenmed [electronic Resource] : Medscape General Medicine. 2002 August 28; 4(3): 8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12466751&dopt=Abstract
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Importance of nonpharmacological factors in nicotine self-administration. Author(s): Caggiula AR, Donny EC, Chaudhri N, Perkins KA, Evans-Martin FF, Sved AF. Source: Physiology & Behavior. 2002 December; 77(4-5): 683-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12527019&dopt=Abstract
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Improved highly sensitive method for determination of nicotine and cotinine in human plasma by high-performance liquid chromatography. Author(s): Nakajima M, Yamamoto T, Kuroiwa Y, Yokoi T. Source: J Chromatogr B Biomed Sci Appl. 2000 May 26; 742(1): 211-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10892601&dopt=Abstract
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In vitro comparative studies of two marketed transdermal nicotine delivery systems: Nicopatch and Nicorette. Author(s): Olivier JC, Rabouan S, Couet W. Source: International Journal of Pharmaceutics. 2003 February 18; 252(1-2): 133-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12550788&dopt=Abstract
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Inactivation gating determines nicotine blockade of human HERG channels. Author(s): Wang HZ, Shi H, Liao SJ, Wang Z. Source: The American Journal of Physiology. 1999 September; 277(3 Pt 2): H1081-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10484431&dopt=Abstract
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Increasing diagnosis of nicotine dependence in adolescent mental health patients. Author(s): Sellman JD, Wootton AR, Stoner DB, Deering DE, Craig BJ. Source: The Australian and New Zealand Journal of Psychiatry. 1999 December; 33(6): 869-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10619214&dopt=Abstract
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Individual differences in nicotine intake per cigarette. Author(s): Patterson F, Benowitz N, Shields P, Kaufmann V, Jepson C, Wileyto P, Kucharski S, Lerman C. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 2003 May; 12(5): 468-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12750245&dopt=Abstract
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Individual differences in smoking: gender and nicotine addiction. Author(s): Shiffman S, Paton SM. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 1999; 1 Suppl 2: S153-7; Discussion S165-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11768174&dopt=Abstract
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Induction of c-fos expression by nicotine in human periodontal ligament fibroblasts is related to cellular thiol levels. Author(s): Chang YC, Hsieh YS, Lii CK, Huang FM, Tai KW, Chou MY. Source: Journal of Periodontal Research. 2003 February; 38(1): 44-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12558936&dopt=Abstract
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Influence of arterial vs. venous sampling site on nicotine tolerance model selection and parameter estimation. Author(s): Schaedeli F, Pitsiu M, Benowitz NL, Gourlay SG, Verotta D. Source: Journal of Pharmacokinetics and Pharmacodynamics. 2002 February; 29(1): 4966. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12194535&dopt=Abstract
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Influence of nicotine on simulator flight performance in non-smokers. Author(s): Mumenthaler MS, Taylor JL, O'Hara R, Yesavage JA. Source: Psychopharmacology. 1998 November; 140(1): 38-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9862400&dopt=Abstract
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Influence of nicotine, cotinine, anabasine and cigarette smoke extract on human granulosa cell progesterone and estradiol synthesis. Author(s): Gocze PM, Szabo I, Freeman DA. Source: Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology. 1999 August; 13(4): 266-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10533162&dopt=Abstract
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Inhibitory effect of Sejin-Eum I/II on nicotine- and cigarette extract-induced cytotoxicity in human lung fibroblast. Author(s): Jin JS, Kim MS, Yi JM, Lee JH, Lee JH, Moon SJ, Jung KP, Lee JK, An NH, Kim HM. Source: Journal of Ethnopharmacology. 2003 May; 86(1): 15-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12686436&dopt=Abstract
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Initial exposure to nicotine in college-age women smokers and never-smokers: a replication and extension. Author(s): Pomerleau CS, Pomerleau OF, Namenek RJ, Marks JL. Source: Journal of Addictive Diseases : the Official Journal of the Asam, American Society of Addiction Medicine. 1999; 18(3): 13-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10507578&dopt=Abstract
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Initial symptoms of nicotine dependence in adolescents. Author(s): DiFranza JR, Rigotti NA, McNeill AD, Ockene JK, Savageau JA, St Cyr D, Coleman M. Source: Tobacco Control. 2000 September; 9(3): 313-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10982576&dopt=Abstract
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Initiation of daily smoking and nicotine dependence in schizophrenia and mood disorders. Author(s): de Leon J, Diaz FJ, Rogers T, Browne D, Dinsmore L. Source: Schizophrenia Research. 2002 July 1; 56(1-2): 47-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12084419&dopt=Abstract
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Intensive smoking cessation counseling versus minimal counseling among hospitalized smokers treated with transdermal nicotine replacement: a randomized trial. Author(s): Simon JA, Carmody TP, Hudes ES, Snyder E, Murray J. Source: The American Journal of Medicine. 2003 May; 114(7): 555-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12753879&dopt=Abstract
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Interacting effects of the serotonin transporter gene and neuroticism in smoking practices and nicotine dependence. Author(s): Lerman C, Caporaso NE, Audrain J, Main D, Boyd NR, Shields PG. Source: Molecular Psychiatry. 2000 March; 5(2): 189-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10822347&dopt=Abstract
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Interactions between alcohol and nicotine dependence: a summary of potential mechanisms and implications for treatment. Author(s): Littleton J, Little H. Source: Alcoholism, Clinical and Experimental Research. 2002 December; 26(12): 1922-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12500121&dopt=Abstract
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Interindividual differences in nicotine metabolism and genetic polymorphisms of human CYP2A6. Author(s): Nakajima M, Kuroiwa Y, Yokoi T. Source: Drug Metabolism Reviews. 2002 November; 34(4): 865-77. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12487152&dopt=Abstract
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Interleukin-8 secretion by cultured oral epidermoid carcinoma cells induced with nicotine and/or arecoline treatments. Author(s): Cheng YA, Shiue LF, Yu HS, Hsieh TY, Tsai CC. Source: Kaohsiung J Med Sci. 2000 March; 16(3): 126-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10846348&dopt=Abstract
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Inter-species consistency in the behavioural pharmacology of nicotine dependence. Author(s): Stolerman IP. Source: Behavioural Pharmacology. 1999 November; 10(6-7): 559-80. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10780497&dopt=Abstract
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Intra-luminal nicotine reduces smooth muscle tone and contractile activity in the distal large bowel. Author(s): Green JT, McKirdy HC, Rhodes J, Thomas GA, Evans BK. Source: European Journal of Gastroenterology & Hepatology. 1999 November; 11(11): 1299-304. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10563544&dopt=Abstract
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Intravenous nicotine and caffeine: subjective and physiological effects in cocaine abusers. Author(s): Garrett BE, Griffiths RR. Source: The Journal of Pharmacology and Experimental Therapeutics. 2001 February; 296(2): 486-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11160635&dopt=Abstract
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Intravenous nicotine reduces cerebral glucose metabolism: a preliminary study. Author(s): Stapleton JM, Gilson SF, Wong DF, Villemagne VL, Dannals RF, Grayson RF, Henningfield JE, London ED. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2003 April; 28(4): 765-72. Epub 2002 November 01. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12655323&dopt=Abstract
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Introduction to tobacco, nicotine, and youth: the tobacco etiology research network. Author(s): Clayton RR, Ries Merikangas K, Abrams DB. Source: Drug and Alcohol Dependence. 2000 May 1; 59 Suppl 1: S1-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10773433&dopt=Abstract
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Investigation of nicotine binding to THP-1 cells: evidence for a non-cholinergic binding site. Author(s): Morgan D, Parsons ME, Whelan CJ. Source: Biochemical Pharmacology. 2001 March 15; 61(6): 733-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11266659&dopt=Abstract
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Involvement of human heat shock protein 90 alpha in nicotine-induced apoptosis. Author(s): Wu YP, Kita K, Suzuki N. Source: International Journal of Cancer. Journal International Du Cancer. 2002 July 1; 100(1): 37-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12115584&dopt=Abstract
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Is dependence on one drug associated with dependence on other drugs? The cases of alcohol, caffeine and nicotine. Author(s): Hughes JR, Oliveto AH, MacLaughlin M. Source: The American Journal on Addictions / American Academy of Psychiatrists in Alcoholism and Addictions. 2000 Summer; 9(3): 196-201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11000915&dopt=Abstract
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Is it the nicotine or the tobacco? Author(s): Sweanor D. Source: Bulletin of the World Health Organization. 2000; 78(7): 943. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10994270&dopt=Abstract
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Is leptin involved in the acute anorectic effect of nicotine? Author(s): Miyata G, Meguid MM. Source: Nutrition (Burbank, Los Angeles County, Calif.). 2000 February; 16(2): 141-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10696640&dopt=Abstract
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Is nicotine dependence related to smokers' support for restrictions on smoking? Author(s): Lacchetti C, Cohen J, Ashley MJ, Ferrence R, Bull S, de Groh M, Pederson L. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2001 August; 3(3): 257-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11506769&dopt=Abstract
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Is telephone counselling a useful addition to physician advice and nicotine replacement therapy in helping patients to stop smoking? A randomized controlled trial. Author(s): Reid RD, Pipe A, Dafoe WA. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 1999 June 1; 160(11): 1577-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10373999&dopt=Abstract
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Kicking the habit. Near-sighted on nicotine? Author(s): Huff C. Source: Hospitals & Health Networks / Aha. 1998 October 5; 72(19): 48. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9823283&dopt=Abstract
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Kinetic analysis of regional (S)(-)11C-nicotine binding in normal and Alzheimer brains--in vivo assessment using positron emission tomography. Author(s): Nordberg A, Lundqvist H, Hartvig P, Lilja A, Langstrom B. Source: Alzheimer Disease and Associated Disorders. 1995 Spring; 9(1): 21-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7605618&dopt=Abstract
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Knowledge of health consequences of nicotinism among secondary school pupils. Young people's attitudes towards passive smoking and their opinions about antinicotine act's regulations. Author(s): Zolnierczuk-Kieliszek D. Source: Ann Univ Mariae Curie Sklodowska [med]. 1999; 54: 217-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11205767&dopt=Abstract
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Lack of effect of nicotine or ethanol on the activity of 11beta-hydroxysteroid dehydrogenase type 2. Author(s): Benediktsson R, Magnusdottir EM, Seckl JR. Source: The Journal of Steroid Biochemistry and Molecular Biology. 1997 NovemberDecember; 63(4-6): 303-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9459196&dopt=Abstract
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Lack of effect of transdermal nicotine on 3 cases of primary sclerosing cholangitis. Author(s): Jorgensen G, Waldum HL. Source: Digestive Diseases and Sciences. 1999 December; 44(12): 2484. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10630501&dopt=Abstract
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Lack of efficacy of transdermal nicotine in smoking cessation. Author(s): Joseph AM, Antonnucio DO. Source: The New England Journal of Medicine. 1999 October 7; 341(15): 1157-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10515763&dopt=Abstract
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Late-term smoking cessation despite initial failure: an evaluation of bupropion sustained release, nicotine patch, combination therapy, and placebo. Author(s): Jamerson BD, Nides M, Jorenby DE, Donahue R, Garrett P, Johnston JA, Fiore MC, Rennard SI, Leischow SJ. Source: Clinical Therapeutics. 2001 May; 23(5): 744-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11394732&dopt=Abstract
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Leptin levels in smokers and long-term users of nicotine gum. Author(s): Eliasson B, Smith U. Source: European Journal of Clinical Investigation. 1999 February; 29(2): 145-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10093001&dopt=Abstract
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Let's not overlook nicotine. Author(s): Roll JM, Higgins ST. Source: Journal of Analytical Toxicology. 1996 March-April; 20(2): 143. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8868410&dopt=Abstract
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Levelling the playing field for regulation of nicotine. Author(s): Kawachi I. Source: Bmj (Clinical Research Ed.). 2003 January 18; 326(7381): 115-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12531820&dopt=Abstract
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Levels of cotinine associated with long-term ad-libitum nicotine polacrilex use in a clinical trial. Author(s): Murray RP, Nides MA, Istvan JA, Daniels K. Source: Addictive Behaviors. 1998 July-August; 23(4): 529-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9698981&dopt=Abstract
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Life-time prevalence and risk factors of tobacco/nicotine dependence in male eversmokers in Japan. Author(s): Kawakami N, Takatsuka N, Shimizu H, Takai A. Source: Addiction (Abingdon, England). 1998 July; 93(7): 1023-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9744133&dopt=Abstract
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Longlasting improvement of Tourette's syndrome with transdermal nicotine. Author(s): Dursun SM, Reveley MA, Bird R, Stirton F. Source: Lancet. 1994 December 3; 344(8936): 1577. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7983976&dopt=Abstract
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Long-term effects of a single course of nicotine treatment in acute ulcerative colitis: remission maintenance in a 12-month follow-up study. Author(s): Guslandi M. Source: International Journal of Colorectal Disease. 1999 November; 14(4-5): 261-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10647637&dopt=Abstract
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Long-term effects of nicotine gum on weight gain after smoking cessation. Author(s): Nordstrom BL, Kinnunen T, Utman CH, Garvey AJ. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 1999 September; 1(3): 259-68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11072423&dopt=Abstract
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Long-term effects of the Eclipse cigarette substitute and the nicotine inhaler in smokers not interested in quitting. Author(s): Fagerstrom KO, Hughes JR, Callas PW. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2002; 4 Suppl 2: S141-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12573175&dopt=Abstract
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Long-term use of nicotine chewing gum and mercury exposure from dental amalgam fillings. Author(s): Sallsten G, Thoren J, Barregard L, Schutz A, Skarping G. Source: Journal of Dental Research. 1996 January; 75(1): 594-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8655765&dopt=Abstract
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Long-term use of nicotine gum is associated with hyperinsulinemia and insulin resistance. Author(s): Eliasson B, Taskinen MR, Smith U. Source: Circulation. 1996 September 1; 94(5): 878-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8790020&dopt=Abstract
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Loss of neonatal hypoxia tolerance after prenatal nicotine exposure: implications for sudden infant death syndrome. Author(s): Slotkin TA, Lappi SE, McCook EC, Lorber BA, Seidler FJ. Source: Brain Research Bulletin. 1995; 38(1): 69-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7552377&dopt=Abstract
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L-tyrosine and nicotine induce synthesis of L-Dopa and norepinephrine in human lymphocytes. Author(s): Musso NR, Brenci S, Indiveri F, Lotti G. Source: Journal of Neuroimmunology. 1997 April; 74(1-2): 117-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9119963&dopt=Abstract
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Lung tissue concentrations of nicotine in sudden infant death syndrome (SIDS). Author(s): McMartin KI, Platt MS, Hackman R, Klein J, Smialek JE, Vigorito R, Koren G. Source: The Journal of Pediatrics. 2002 February; 140(2): 205-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11865272&dopt=Abstract
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Malignant potential of palatoglossal, nicotine stomatitis. A study amongst smokers. Author(s): Kurian K, Dayal PK. Source: Indian J Dent Res. 1996 April-June; 7(2): 55-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9495100&dopt=Abstract
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Managing nicotine addiction. Author(s): Kotlyar M, Hatsukami DK. Source: J Dent Educ. 2002 September; 66(9): 1061-73. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12374267&dopt=Abstract
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Managing nicotine dependence. Author(s): Kottke TE. Source: Journal of the American College of Cardiology. 1997 July; 30(1): 131-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9207633&dopt=Abstract
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Maternal nicotine exposure upregulates collagen gene expression in fetal monkey lung. Association with alpha7 nicotinic acetylcholine receptors. Author(s): Sekhon HS, Keller JA, Proskocil BJ, Martin EL, Spindel ER. Source: American Journal of Respiratory Cell and Molecular Biology. 2002 January; 26(1): 31-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11751201&dopt=Abstract
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Maternal smoking during pregnancy and nicotine and cotinine concentrations in maternal and neonatal hair. Author(s): Jacqz-Aigrain E, Zhang D, Maillard G, Luton D, Andre J, Oury JF. Source: Bjog : an International Journal of Obstetrics and Gynaecology. 2002 August; 109(8): 909-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12197371&dopt=Abstract
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Maternal transmission of nicotine dependence: psychiatric, neurocognitive and prenatal factors. Author(s): Niaura R, Bock B, Lloyd EE, Brown R, Lipsitt LP, Buka S. Source: The American Journal on Addictions / American Academy of Psychiatrists in Alcoholism and Addictions. 2001 Winter; 10(1): 16-29. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11268825&dopt=Abstract
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Measurement and analysis of nicotine and other VOCs in indoor air as an indicator of passive smoking. Author(s): Rothberg M, Heloma A, Svinhufvud J, Kahkonen E, Reijula K. Source: The Annals of Occupational Hygiene. 1998 February; 42(2): 129-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9559573&dopt=Abstract
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Measurement of nicotine in hair by reversed-phase high-performance liquid chromatography with electrochemical detection. Author(s): Mahoney GN, Al-Delaimy W. Source: J Chromatogr B Biomed Sci Appl. 2001 April 5; 753(2): 179-87. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11334330&dopt=Abstract
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Measurement of nicotine intake in pregnant women--associations to changes in blood cell count. Author(s): Cope GF, Nayyar P, Holder R. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2001 May; 3(2): 119-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11403725&dopt=Abstract
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Measuring nicotine dependence among high-risk adolescent smokers. Author(s): Prokhorov AV, Pallonen UE, Fava JL, Ding L, Niaura R. Source: Addictive Behaviors. 1996 January-February; 21(1): 117-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8729713&dopt=Abstract
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Measuring nicotine dependence among youth: a review of available approaches and instruments. Author(s): Colby SM, Tiffany ST, Shiffman S, Niaura RS. Source: Drug and Alcohol Dependence. 2000 May 1; 59 Suppl 1: S23-39. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10773436&dopt=Abstract
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Measuring nicotine intake in population surveys: comparability of saliva cotinine and plasma cotinine estimates. Author(s): Jarvis MJ, Primatesta P, Erens B, Feyerabend C, Bryant A. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2003 June; 5(3): 349-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12791530&dopt=Abstract
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Measuring the loss of autonomy over nicotine use in adolescents: the DANDY (Development and Assessment of Nicotine Dependence in Youths) study. Author(s): DiFranza JR, Savageau JA, Fletcher K, Ockene JK, Rigotti NA, McNeill AD, Coleman M, Wood C. Source: Archives of Pediatrics & Adolescent Medicine. 2002 April; 156(4): 397-403. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11929376&dopt=Abstract
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Mecamylamine (a nicotine antagonist) for smoking cessation. Author(s): Cochrane Database Syst Rev. 2001;(2):CD001749 Source: Cochrane Database Syst Rev. 2000; (2): Cd001009. Review. /entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11406005
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Mecamylamine blockade of both positive and negative effects of IV nicotine in human volunteers. Author(s): Lundahl LH, Henningfield JE, Lukas SE. Source: Pharmacology, Biochemistry, and Behavior. 2000 July; 66(3): 637-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10899382&dopt=Abstract
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Mecamylamine combined with nicotine skin patch facilitates smoking cessation beyond nicotine patch treatment alone. Author(s): Rose JE, Behm FM, Westman EC, Levin ED, Stein RM, Ripka GV. Source: Clinical Pharmacology and Therapeutics. 1994 July; 56(1): 86-99. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8033499&dopt=Abstract
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Mecamylamine inhibits nicotine but not capsaicin irritation on the tongue: psychophysical evidence that nicotine and capsaicin activate separate molecular receptors. Author(s): Dessirier JM, O'Mahony M, Sieffermann JM, Carstens E. Source: Neuroscience Letters. 1998 January 9; 240(2): 65-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9486473&dopt=Abstract
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Mechanism of nicotine-evoked release of 3H-noradrenaline in human cerebral cortex slices. Author(s): Woo RS, Park EY, Shin MS, Jeong MS, Zhao RJ, Shin BS, Kim CJ, Park JW, Kim KW. Source: British Journal of Pharmacology. 2002 December; 137(7): 1063-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12429579&dopt=Abstract
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Mechanisms of alcohol-nicotine interactions: alcoholics versus smokers. Author(s): Narahashi T, Soderpalm B, Ericson M, Olausson P, Engel JA, Zhang X, Nordberg A, Marszalec W, Aistrup GL, Schmidt LG, Kalouti U, Smolka And M, Hedlund L. Source: Alcoholism, Clinical and Experimental Research. 2001 May; 25(5 Suppl Isbra): 152S-156S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11391065&dopt=Abstract
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Mechanisms of cytotoxicity of nicotine in human periodontal ligament fibroblast cultures in vitro. Author(s): Chang YC, Huang FM, Tai KW, Yang LC, Chou MY. Source: Journal of Periodontal Research. 2002 August; 37(4): 279-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12200972&dopt=Abstract
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Mechanisms of mitogen-activated protein kinase activation by nicotine in small-cell lung carcinoma cells. Author(s): Cattaneo MG, D'atri F, Vicentini LM. Source: The Biochemical Journal. 1997 December 1; 328 ( Pt 2): 499-503. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9371707&dopt=Abstract
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Melatonin treatment attenuates symptoms of acute nicotine withdrawal in humans. Author(s): Zhdanova IV, Piotrovskaya VR. Source: Pharmacology, Biochemistry, and Behavior. 2000 September; 67(1): 131-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11113492&dopt=Abstract
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Metabolism of nicotine to cotinine studied by a dual stable isotope method. Author(s): Benowitz NL, Jacob P 3rd. Source: Clinical Pharmacology and Therapeutics. 1994 November; 56(5): 483-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7955812&dopt=Abstract
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Methodological considerations in nicotine research: the use of "denicotinised" cigarettes as the control condition in smoking studies. Author(s): Rusted JM, Graupner L, Greenwood K. Source: Psychopharmacology. 1996 May; 125(2): 176-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8783392&dopt=Abstract
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Microarray analysis of nicotine-induced changes in gene expression in endothelial cells. Author(s): Zhang S, Day IN, Ye S. Source: Physiological Genomics. 2001 April 27; 5(4): 187-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11328964&dopt=Abstract
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Microarray technology and its application on nicotine research. Author(s): Li MD, Konu O, Kane JK, Becker KG. Source: Molecular Neurobiology. 2002 June; 25(3): 265-85. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12109875&dopt=Abstract
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Microdialysis in cutaneous pharmacology: kinetic analysis of transdermally delivered nicotine. Author(s): Hegemann L, Forstinger C, Partsch B, Lagler I, Krotz S, Wolff K. Source: The Journal of Investigative Dermatology. 1995 May; 104(5): 839-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7738365&dopt=Abstract
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Microsomal N-glucuronidation of nicotine and cotinine: human hepatic interindividual, human intertissue, and interspecies hepatic variation. Author(s): Ghosheh O, Hawes EM. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2002 December; 30(12): 1478-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12433822&dopt=Abstract
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Minnesota settlement, documents in mind-boggling numbers, smoke-free Birmingham, fire-safe cigarettes, Surgeon General's report, nicotine yields, cigars, Tasmania, and a Marlboro Gear spoof. Author(s): Cannon J. Source: Tobacco Control. 1998 Summer; 7(2): 189-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9789939&dopt=Abstract
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Modeling nicotine arterial-venous differences to predict arterial concentrations and input based on venous measurements: application to smokeless tobacco and nicotine gum. Author(s): Pitsiu M, Gries JM, Benowitz N, Gourlay SG, Verotta D. Source: Journal of Pharmacokinetics and Pharmacodynamics. 2002 August; 29(4): 383402. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12518710&dopt=Abstract
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Molecular and cellular aspects of nicotine abuse. Author(s): Dani JA, Heinemann S. Source: Neuron. 1996 May; 16(5): 905-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8630247&dopt=Abstract
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Molecular mechanisms of the positive reinforcing effect of nicotine. Author(s): Merlo Pich E, Chiamulera C, Carboni L. Source: Behavioural Pharmacology. 1999 November; 10(6-7): 587-96. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10780500&dopt=Abstract
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Molecular orbital calculations and nicotine metabolism: a rationale for experimentally observed metabolite ratios. Author(s): Lewis DF, Gorrod JW. Source: Drug Metabol Drug Interact. 2002; 19(1): 29-39. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12222752&dopt=Abstract
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Mood and physiological effects of subcutaneous nicotine in smokers and neversmokers. Author(s): Foulds J, Stapleton JA, Bell N, Swettenham J, Jarvis MJ, Russell MA. Source: Drug and Alcohol Dependence. 1997 March 14; 44(2-3): 105-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9088782&dopt=Abstract
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Mood management and nicotine gum in smoking treatment: a therapeutic contact and placebo-controlled study. Author(s): Hall SM, Munoz RF, Reus VI, Sees KL, Duncan C, Humfleet GL, Hartz DT. Source: Journal of Consulting and Clinical Psychology. 1996 October; 64(5): 1003-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8916629&dopt=Abstract
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Moving out of the laboratory: does nicotine improve everyday attention? Author(s): Rusted JM, Caulfield D, King L, Goode A. Source: Behavioural Pharmacology. 2000 November; 11(7-8): 621-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11198133&dopt=Abstract
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Multimodal assessment of the effect of chewing gum on nicotine withdrawal. Author(s): Cohen LM, Britt DM, Collins FL, Al'Absi M, McChargue DE. Source: Addictive Behaviors. 2001 March-April; 26(2): 289-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11316385&dopt=Abstract
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Multiple risk factors for the initiation of smoking: the public health imperative for multidisciplinary genetic epidemiological investigations of nicotine addiction. Author(s): Swan GE. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 1999; 1 Suppl 2: S71-3; Discussion S69-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11768190&dopt=Abstract
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Multiple substance dependence: implications for treatment of nicotine dependence. Author(s): West R. Source: Addiction (Abingdon, England). 2001 May; 96(5): 775-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11370642&dopt=Abstract
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Naturalistic, self-assignment comparative trial of bupropion SR, a nicotine patch, or both for smoking cessation treatment in primary care. Author(s): Gold PB, Rubey RN, Harvey RT. Source: The American Journal on Addictions / American Academy of Psychiatrists in Alcoholism and Addictions. 2002 Fall; 11(4): 315-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12584874&dopt=Abstract
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N-glucuronidation of nicotine and cotinine in human: formation of cotinine glucuronide in liver microsomes and lack of catalysis by 10 examined UDPglucuronosyltransferases. Author(s): Ghosheh O, Hawes EM. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2002 September; 30(9): 991-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12167564&dopt=Abstract
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Nicotine addiction, young adults, and smoke-free bars. Author(s): Ling PM, Glantz SA. Source: Drug and Alcohol Review. 2002 June; 21(2): 101-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12188987&dopt=Abstract
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Nicotine and behavioral markers of risk for schizophrenia: a double-blind, placebocontrolled, cross-over study. Author(s): Depatie L, O'Driscoll GA, Holahan AL, Atkinson V, Thavundayil JX, Kin NN, Lal S. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2002 December; 27(6): 1056-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12464463&dopt=Abstract
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Nicotine and familial vulnerability to schizophrenia: a discordant twin study. Author(s): Lyons MJ, Bar JL, Kremen WS, Toomey R, Eisen SA, Goldberg J, Faraone SV, Tsuang M. Source: Journal of Abnormal Psychology. 2002 November; 111(4): 687-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12428784&dopt=Abstract
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Nicotine and neurodegeneration in ageing. Author(s): Zanardi A, Leo G, Biagini G, Zoli M. Source: Toxicology Letters. 2002 February 28; 127(1-3): 207-15. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12052660&dopt=Abstract
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Nicotine and nicotinic receptors; relevance to Parkinson's disease. Author(s): Quik M, Kulak JM. Source: Neurotoxicology. 2002 October; 23(4-5): 581-94. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12428730&dopt=Abstract
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Nicotine as a modulator of behavior: beyond the inverted U. Author(s): Picciotto MR. Source: Trends in Pharmacological Sciences. 2003 September; 24(9): 493-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12967775&dopt=Abstract
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Nicotine concentrations in deciduous teeth and cumulative exposure to tobacco smoke during childhood. Author(s): Garcia-Algar O, Vall O, Segura J, Pascual JA, Diaz D, Mutnoz L, Zuccaro P, Pacifici R, Pichini S. Source: Jama : the Journal of the American Medical Association. 2003 July 9; 290(2): 1967. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12851273&dopt=Abstract
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Nicotine concentrations with concurrent use of cigarettes and nicotine replacement: a review. Author(s): Fagerstrom KO, Hughes JR. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2002; 4 Suppl 2: S73-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12573169&dopt=Abstract
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Nicotine consumption before and during pregnancy affects not only newborn size but also birth modus. Author(s): Kirchengast S, Hartmann B. Source: Journal of Biosocial Science. 2003 April; 35(2): 175-88. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12664956&dopt=Abstract
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Nicotine delivery from smoking bidis and an additive-free cigarette. Author(s): Malson JL, Lee EM, Moolchan ET, Pickworth WB. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2002 November; 4(4): 485-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12521408&dopt=Abstract
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Nicotine dependence and treatment outcome among African American cocainedependent patients. Author(s): Patkar AA, Vergare MJ, Thornton CC, Weinstein SP, Murray HW, Leone FT. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2003 June; 5(3): 411-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12791537&dopt=Abstract
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Nicotine dependence treatment for patients with cancer. Author(s): Cox LS, Africano NL, Tercyak KP, Taylor KL. Source: Cancer. 2003 August 1; 98(3): 632-44. Review. Erratum In: Cancer. 2003 September 1; 98(5): 1104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12879483&dopt=Abstract
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Nicotine dependence: development, mechanisms, individual differences and links to possible neurophysiological correlates. Author(s): Groman E, Fagerstrom K. Source: Wiener Klinische Wochenschrift. 2003 March 31; 115(5-6): 155-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12741073&dopt=Abstract
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Nicotine dependence: the role for antidepressants and anxiolytics. Author(s): Sullivan MA, Covey LS. Source: Curr Opin Investig Drugs. 2002 February; 3(2): 262-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12020058&dopt=Abstract
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Nicotine deprivation effects on the dissociated components of simple reaction time. Author(s): Marzilli TS, Hutcherson AB. Source: Percept Mot Skills. 2002 June; 94(3 Pt 1): 985-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12081303&dopt=Abstract
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Nicotine effects on alertness and spatial attention in non-smokers. Author(s): Griesar WS, Zajdel DP, Oken BS. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2002 May; 4(2): 185-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12028851&dopt=Abstract
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Nicotine exposure and bronchial epithelial cell nicotinic acetylcholine receptor expression in the pathogenesis of lung cancer. Author(s): Minna JD. Source: The Journal of Clinical Investigation. 2003 January; 111(1): 31-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12511585&dopt=Abstract
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Nicotine gum-induced atrial fibrillation. Author(s): Choragudi NL, Aronow WS, DeLuca AJ. Source: Heart Disease. 2003 March-April; 5(2): 100-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12713677&dopt=Abstract
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Nicotine has suppressive effects on dendritic cell function. Author(s): Hogg N. Source: Immunology. 2003 July; 109(3): 329-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12807476&dopt=Abstract
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Nicotine increases oxidative stress, activates NF-kappaB and GRP78, induces apoptosis and sensitizes cells to genotoxic/xenobiotic stresses by a multiple stress inducer, deoxycholate: relevance to colon carcinogenesis. Author(s): Crowley-Weber CL, Dvorakova K, Crowley C, Bernstein H, Bernstein C, Garewal H, Payne CM. Source: Chemico-Biological Interactions. 2003 March 6; 145(1): 53-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12606154&dopt=Abstract
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Nicotine intervention during detoxification and treatment for other substance use. Author(s): Gariti P, Alterman A, Mulvaney F, Mechanic K, Dhopesh V, Yu E, Chychula N, Sacks D. Source: The American Journal of Drug and Alcohol Abuse. 2002 November; 28(4): 671-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12492263&dopt=Abstract
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Nicotine lozenge trial: a "Real-World" perspective. Author(s): Walsh RA. Source: Archives of Internal Medicine. 2002 December 9-23; 162(22): 2632-3; Author Reply 2633. Erratum In: Arch Intern Med. 2003 March 10; 163(5): 571. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12456245&dopt=Abstract
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Nicotine metabolism, human drug metabolism polymorphisms, and smoking behaviour. Author(s): Tricker AR. Source: Toxicology. 2003 February 1; 183(1-3): 151-73. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12504349&dopt=Abstract
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Nicotine modulates the expression of a diverse set of genes in the neuronal SH-SY5Y cell line. Author(s): Dunckley T, Lukas RJ. Source: The Journal of Biological Chemistry. 2003 May 2; 278(18): 15633-40. Epub 2003 February 14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12588870&dopt=Abstract
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Nicotine modulation of in vitro human gingival fibroblast beta1 integrin expression. Author(s): Snyder HB, Caughman G, Lewis J, Billman MA, Schuster G. Source: J Periodontol. 2002 May; 73(5): 505-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12027252&dopt=Abstract
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Nicotine patch therapy based on smoking rate followed by bupropion for prevention of relapse to smoking. Author(s): Hurt RD, Krook JE, Croghan IT, Loprinzi CL, Sloan JA, Novotny PJ, Kardinal CG, Knost JA, Tirona MT, Addo F, Morton RF, Michalak JC, Schaefer PL, Porter PA, Stella PJ. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 March 1; 21(5): 914-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12610193&dopt=Abstract
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Nicotine patches and the subjective effects of cigarette smoking: a pilot study. Author(s): Cardenas L, Busto UE, MacDonald A, Corrigall WA. Source: Can J Clin Pharmacol. 2002 Winter; 9(4): 175-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12584575&dopt=Abstract
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Nicotine permeability across the buccal TR146 cell culture model and porcine buccal mucosa in vitro: effect of pH and concentration. Author(s): Nielsen HM, Rassing MR. Source: European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences. 2002 August; 16(3): 151-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12128169&dopt=Abstract
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Nicotine promotes arteriogenesis. Author(s): Heeschen C, Weis M, Cooke JP. Source: Journal of the American College of Cardiology. 2003 February 5; 41(3): 489-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12575981&dopt=Abstract
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Nicotine reduces the secretion of Alzheimer's beta-amyloid precursor protein containing beta-amyloid peptide in the rat without altering synaptic proteins. Author(s): Lahiri DK, Utsuki T, Chen D, Farlow MR, Shoaib M, Ingram DK, Greig NH. Source: Annals of the New York Academy of Sciences. 2002 June; 965: 364-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12105112&dopt=Abstract
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Nicotine replacement therapy for smoking cessation. Author(s): Silagy C, Lancaster T, Stead L, Mant D, Fowler G. Source: Cochrane Database Syst Rev. 2002; (4): Cd000146. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12519537&dopt=Abstract
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Nicotine replacement therapy in smoking cessation. Author(s): Campbell I. Source: Thorax. 2003 June; 58(6): 464-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12775853&dopt=Abstract
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Nicotine replacement to reduce cigarette consumption in smokers who are unwilling to quit: a randomized trial. Author(s): Etter JF, Laszlo E, Zellweger JP, Perrot C, Perneger TV. Source: Journal of Clinical Psychopharmacology. 2002 October; 22(5): 487-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12352272&dopt=Abstract
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Nicotine strongly activates dendritic cell-mediated adaptive immunity: potential role for progression of atherosclerotic lesions. Author(s): Aicher A, Heeschen C, Mohaupt M, Cooke JP, Zeiher AM, Dimmeler S. Source: Circulation. 2003 February 4; 107(4): 604-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12566374&dopt=Abstract
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Nicotine withdrawal and depressive symptomatology during short-term smoking abstinence: a comparison of postmenopausal women using and not using hormone replacement therapy. Author(s): Allen SS, Hatsukami DK, Christianson D. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2003 February; 5(1): 49-59. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745506&dopt=Abstract
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Nicotine, body weight and potential implications in the treatment of obesity. Author(s): Li MD, Kane JK, Konu O. Source: Current Topics in Medicinal Chemistry. 2003; 3(8): 899-919. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12678839&dopt=Abstract
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Nicotine, serotonin, and sudden infant death syndrome. Author(s): Nattie E, Kinney H. Source: American Journal of Respiratory and Critical Care Medicine. 2002 December 15; 166(12 Pt 1): 1530-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12471066&dopt=Abstract
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Nicotine-induced Ca2+ signaling and down-regulation of nicotinic acetylcholine receptor subunit expression in the CEM human leukemic T-cell line. Author(s): Kimura R, Ushiyama N, Fujii T, Kawashima K. Source: Life Sciences. 2003 March 28; 72(18-19): 2155-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12628473&dopt=Abstract
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Objective measurements of nicotine exposure in victims of sudden infant death syndrome and in other unexpected child deaths. Author(s): Milerad J, Vege A, Opdal SH, Rognum TO. Source: The Journal of Pediatrics. 1998 August; 133(2): 232-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9709711&dopt=Abstract
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Olfactory thresholds for nicotine and menthol in smokers (abstinent and nonabstinent) and nonsmokers. Author(s): Rosenblatt MR, Olmstead RE, Iwamoto-Schaap PN, Jarvik ME. Source: Physiology & Behavior. 1998 December 1; 65(3): 575-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9877426&dopt=Abstract
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Onset of major depression during treatment for nicotine dependence. Author(s): Killen JD, Fortmann SP, Schatzberg A, Hayward C, Varady A. Source: Addictive Behaviors. 2003 April; 28(3): 461-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12628619&dopt=Abstract
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Open randomised trial of intermittent very low energy diet together with nicotine gum for stopping smoking in women who gained weight in previous attempts to quit. Author(s): Danielsson T, Rossner S, Westin A. Source: Bmj (Clinical Research Ed.). 1999 August 21; 319(7208): 490-3; Discussion 494. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10454403&dopt=Abstract
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Opioids induce while nicotine suppresses apoptosis in human lung cancer cells. Author(s): Maneckjee R, Minna JD. Source: Cell Growth & Differentiation : the Molecular Biology Journal of the American Association for Cancer Research. 1994 October; 5(10): 1033-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7848904&dopt=Abstract
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Opioids suppress basal and nicotine-induced catecholamine secretion via a stabilizing effect on actin filaments. Author(s): Dermitzaki E, Gravanis A, Venihaki M, Stournaras C, Margioris AN. Source: Endocrinology. 2001 May; 142(5): 2022-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11316769&dopt=Abstract
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Oral caffeine maintenance potentiates the reinforcing and stimulant subjective effects of intravenous nicotine in cigarette smokers. Author(s): Jones HE, Griffiths RR. Source: Psychopharmacology. 2003 January; 165(3): 280-90. Epub 2002 November 14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12434259&dopt=Abstract
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Oral irritant effects of nicotine. Psychophysical evidence for decreased sensation following repeated application of and lack of cross-desensitization to capsaicin. Author(s): Dessirier JM, O'Mahony M, Carstens E. Source: Annals of the New York Academy of Sciences. 1998 November 30; 855: 828-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9929695&dopt=Abstract
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Oral irritant effects of nicotine: psychophysical evidence for decreased sensation following repeated application and lack of cross-desensitization to capsaicin. Author(s): Dessirier JM, O'Mahony M, Carstens E. Source: Chemical Senses. 1997 October; 22(5): 483-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9363348&dopt=Abstract
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Oral irritant properties of menthol: sensitizing and desensitizing effects of repeated application and cross-desensitization to nicotine. Author(s): Dessirier JM, O'Mahony M, Carstens E. Source: Physiology & Behavior. 2001 May; 73(1-2): 25-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11399291&dopt=Abstract
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Oral irritant properties of piperine and nicotine: psychophysical evidence for asymmetrical desensitization effects. Author(s): Dessirier JM, Nguyen N, Sieffermann JM, Carstens E, O'Mahony M. Source: Chemical Senses. 1999 August; 24(4): 405-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10480676&dopt=Abstract
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Oral nicotine in treatment of primary sclerosing cholangitis: a pilot study. Author(s): Angulo P, Bharucha AE, Jorgensen RA, DeSotel CK, Sandborn WJ, Larusso NF, Lindor KD. Source: Digestive Diseases and Sciences. 1999 March; 44(3): 602-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10080157&dopt=Abstract
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Oral nicotine solution for smoking cessation: a pilot tolerability study. Author(s): Westman EC, Tomlin KF, Perkins CE, Rose JE. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2001 November; 3(4): 391-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11694207&dopt=Abstract
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OTC nicotine gum. Author(s): McKenna JP. Source: The Journal of Family Practice. 1995 January; 40(1): 16; Author Reply 16-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7807029&dopt=Abstract
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OTC nicotine gum. Author(s): Glover ED. Source: The Journal of Family Practice. 1995 January; 40(1): 15-6; Author Reply 16-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7807028&dopt=Abstract
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Outcome of ulcerative colitis after treatment with transdermal nicotine. Author(s): Guslandi M, Tittobello A. Source: European Journal of Gastroenterology & Hepatology. 1998 June; 10(6): 513-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9855069&dopt=Abstract
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Overcoming barriers to nicotine dependence treatment. Author(s): Ferry LH. Source: Primary Care. 1999 September; 26(3): 707-46. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10436295&dopt=Abstract
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Over-the-counter nicotine patch therapy for smoking cessation: results from randomized, double-blind, placebo-controlled, and open label trials. Author(s): Hays JT, Croghan IT, Schroeder DR, Offord KP, Hurt RD, Wolter TD, Nides MA, Davidson M. Source: American Journal of Public Health. 1999 November; 89(11): 1701-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10553392&dopt=Abstract
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Passive exposure to tobacco smoke: hair nicotine levels in preschool children. Author(s): Kalinic N, Skender Lj, Karacic V, Brcic I, Vadjic V. Source: Bulletin of Environmental Contamination and Toxicology. 2003 July; 71(1): 1-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12945833&dopt=Abstract
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Passive smoking in children: effect of avoidance strategies, at home as measured by hair nicotine levels. Author(s): Al-Delaimy WK, Crane J, Woodward A. Source: Archives of Environmental Health. 2001 March-April; 56(2): 117-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11339674&dopt=Abstract
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Pathophysiological effects of nicotine on the pancreas: an update. Author(s): Chowdhury P, MacLeod S, Udupa KB, Rayford PL. Source: Experimental Biology and Medicine (Maywood, N.J.). 2002 July; 227(7): 445-54. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12094008&dopt=Abstract
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Peculiar vulnerability to nicotine oral self-administration in mice during early adolescence. Author(s): Adriani W, Macri S, Pacifici R, Laviola G. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2002 August; 27(2): 212-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12093595&dopt=Abstract
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Permeation studies comparing cobra skin with human skin using nicotine transdermal patches. Author(s): Pongjanyakul T, Prakongpan S, Priprem A. Source: Drug Development and Industrial Pharmacy. 2000 June; 26(6): 635-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10826111&dopt=Abstract
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Persistence of cigarette smoking: familial liability and the role of nicotine dependence. Author(s): Johnson EO, Chase GA, Breslau N. Source: Addiction (Abingdon, England). 2002 August; 97(8): 1063-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12144609&dopt=Abstract
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Persistent and delayed behavioral changes after nicotine treatment in adolescent rats. Author(s): Trauth JA, Seidler FJ, Slotkin TA. Source: Brain Research. 2000 October 13; 880(1-2): 167-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11033001&dopt=Abstract
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Personal exposure to environmental tobacco smoke: salivary cotinine, airborne nicotine, and nonsmoker misclassification. Author(s): Jenkins RA, Counts RW. Source: Journal of Exposure Analysis and Environmental Epidemiology. 1999 JulyAugust; 9(4): 352-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10489160&dopt=Abstract
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PET studies of the influences of nicotine on neural systems in cigarette smokers. Author(s): Rose JE, Behm FM, Westman EC, Mathew RJ, London ED, Hawk TC, Turkington TG, Coleman RE. Source: The American Journal of Psychiatry. 2003 February; 160(2): 323-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12562580&dopt=Abstract
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Pharmacokinetic investigation of a nicotine sublingual tablet. Author(s): Molander L, Lunell E. Source: European Journal of Clinical Pharmacology. 2001 January-February; 56(11): 8139. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11294371&dopt=Abstract
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Pharmacokinetics and pharmacodynamic effects of nicotine nasal spray devices on cardiovascular and pulmonary function. Author(s): Fishbein L, O'Brien P, Hutson A, Theriaque D, Stacpoole PW, Flotte T. Source: Journal of Investigative Medicine : the Official Publication of the American Federation for Clinical Research. 2000 November; 48(6): 435-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11094866&dopt=Abstract
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Pharmacokinetics of nicotine in healthy elderly people. Author(s): Molander L, Hansson A, Lunell E. Source: Clinical Pharmacology and Therapeutics. 2001 January; 69(1): 57-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11180039&dopt=Abstract
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Pharmacokinetics of nicotine in kidney failure. Author(s): Molander L, Hansson A, Lunell E, Alainentalo L, Hoffmann M, Larsson R. Source: Clinical Pharmacology and Therapeutics. 2000 September; 68(3): 250-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11014406&dopt=Abstract
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Pharmacologic therapy for nicotine addiction. Author(s): DeGraff AC Jr. Source: Chest. 2002 August; 122(2): 392-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12171803&dopt=Abstract
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Pharmacologic treatments for the nicotine dependent smoker. Author(s): Glover ED, Glover PN. Source: American Journal of Health Behavior. 2001 May-June; 25(3): 179-82. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11322615&dopt=Abstract
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Pharmacology of neuronal nicotinic acetylcholine recceptors: effects of acute and chronic nicotine. Author(s): Kellar KJ, Davila-Garcia MI, Xiao Y. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 1999; 1 Suppl 2: S117-20; Discussion S139-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11768167&dopt=Abstract
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Pharmacotherapy of nicotine dependence. Author(s): Haustein KO. Source: Int J Clin Pharmacol Ther. 2000 June; 38(6): 273-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10890576&dopt=Abstract
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Plasma leptin concentrations and lipid profiles during nicotine abstinence. Author(s): Oeser A, Goffaux J, Snead W, Carlson MG. Source: The American Journal of the Medical Sciences. 1999 September; 318(3): 152-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10487405&dopt=Abstract
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Posttraumatic stress disorder and the incidence of nicotine, alcohol, and other drug disorders in persons who have experienced trauma. Author(s): Breslau N, Davis GC, Schultz LR. Source: Archives of General Psychiatry. 2003 March; 60(3): 289-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12622662&dopt=Abstract
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Potentiation of nicotine reward by alcohol. Author(s): Rose JE, Brauer LH, Behm FM, Cramblett M, Calkins K, Lawhon D. Source: Alcoholism, Clinical and Experimental Research. 2002 December; 26(12): 1930-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12500124&dopt=Abstract
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Predicting smoking cessation and major depression in nicotine-dependent smokers. Author(s): Breslau N, Johnson EO. Source: American Journal of Public Health. 2000 July; 90(7): 1122-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10897192&dopt=Abstract
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Predictors and timing of adverse experiences during trandsdermal nicotine therapy. Author(s): Gourlay SG, Forbes A, Marriner T, McNeil JJ. Source: Drug Safety : an International Journal of Medical Toxicology and Drug Experience. 1999 June; 20(6): 545-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10392670&dopt=Abstract
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Prenatal effects of maternal smoking on daughters' smoking: nicotine or testosterone exposure? Author(s): Kandel DB, Udry JR. Source: American Journal of Public Health. 1999 September; 89(9): 1377-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10474556&dopt=Abstract
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Prenatal exposure to nicotine impairs protective responses of rat pups to hypoxia in an age-dependent manner. Author(s): Fewell JE, Smith FG, Ng VK. Source: Respiration Physiology. 2001 August; 127(1): 61-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11445201&dopt=Abstract
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Prenatal nicotine alters vigilance states and AchR gene expression in the neonatal rat: implications for SIDS. Author(s): Frank MG, Srere H, Ledezma C, O'Hara B, Heller HC. Source: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 2001 April; 280(4): R1134-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11247836&dopt=Abstract
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Prenatal nicotine exposure and abnormal lung function. Author(s): Pierce RA, Nguyen NM. Source: American Journal of Respiratory Cell and Molecular Biology. 2002 January; 26(1): 10-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11751198&dopt=Abstract
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Prescription of transdermal nicotine patches for smoking cessation in general practice: evaluation of cost-effectiveness. Author(s): Stapleton JA, Lowin A, Russell MA. Source: Lancet. 1999 July 17; 354(9174): 210-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10421303&dopt=Abstract
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Prevalence of nicotine consumption in drug deaths. Author(s): Hafezi M, Bohnert M, Weinmann W, Pollak S. Source: Forensic Science International. 2001 July 15; 119(3): 284-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11390141&dopt=Abstract
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Prevalence of smokers and nicotine-addicted patients in a suburban emergency department. Author(s): Richman PB, Dinowitz S, Nashed A, Eskin B, Cody R. Source: Academic Emergency Medicine : Official Journal of the Society for Academic Emergency Medicine. 1999 August; 6(8): 807-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10463552&dopt=Abstract
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Prevention of lung cancer by long-term use of alternative nicotine delivery systems? Author(s): Kunze U, Schmeiser-Rieder A, Schoberberger R. Source: European Journal of Cancer (Oxford, England : 1990). 1999 February; 35(2): 1956. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10448258&dopt=Abstract
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Prevention of nicotine addiction: neuropsychopharmacological issues. Author(s): Henningfield JE, Jude NR. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 1999; (1 Suppl 1): S41-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11072403&dopt=Abstract
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Probabilities of alcohol high-risk drinking, abuse or dependence estimated on grounds of tobacco smoking and nicotine dependence. Author(s): John U, Meyer C, Rumpf HJ, Hapke U. Source: Addiction (Abingdon, England). 2003 June; 98(6): 805-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12780369&dopt=Abstract
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Production of endothelin by cultured human endothelial cells following exposure to nicotine or caffeine. Author(s): Lee WO, Wright SM. Source: Metabolism: Clinical and Experimental. 1999 July; 48(7): 845-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10421223&dopt=Abstract
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Progress in nicotine and tobacco research. Author(s): Eissenberg T. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2002 August; 4(3): 355-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12215245&dopt=Abstract
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Prolonged nicotine patch use in quitters with past abstinence-induced depressed mood. Author(s): Pomerleau OF, Pomerleau CS, Marks JL, Snedecor SM, Mehringer AM, Namenek Brouwer RJ, Saules KK. Source: Journal of Substance Abuse Treatment. 2003 January; 24(1): 13-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12646326&dopt=Abstract
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Protease activity induced by nicotine in human cells. Author(s): Wang XL, Kita K, Takahashi S, Hasegawa R, Chi XJ, Yamamori H, Nakajima N, Yokoe H, Tanzawa H, Suzuki N. Source: International Journal of Molecular Medicine. 1999 November; 4(5): 537-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10534577&dopt=Abstract
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Psychoactive drugs and pilot performance: a comparison of nicotine, donepezil, and alcohol effects. Author(s): Mumenthaler MS, Yesavage JA, Taylor JL, O'Hara R, Friedman L, Lee H, Kraemer HC. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2003 July; 28(7): 1366-73. Epub 2003 May 14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12784106&dopt=Abstract
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Psychophysiological effects of nicotine abstinence and behavioral challenges in habitual smokers. Author(s): al'Absi M, Amunrud T, Wittmers LE. Source: Pharmacology, Biochemistry, and Behavior. 2002 June; 72(3): 707-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12175468&dopt=Abstract
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Psychosocial correlates of nicotine dependence among men and women in the U.S. naval services. Author(s): Hourani LL, Yuan H, Bray RM, Vincus AA. Source: Addictive Behaviors. 1999 July-August; 24(4): 521-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10466847&dopt=Abstract
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Psychosocial versus nicotine-only self-report measures for predicting follow-up smoking status. Author(s): McCarthy WJ, Zhou Y, Hser YI. Source: Journal of Behavioral Medicine. 2001 February; 24(1): 75-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11296471&dopt=Abstract
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Quantitation of 4-oxo-4-(3-pyridyl)butanoic acid and enantiomers of 4-hydroxy-4-(3pyridyl)butanoic acid in human urine: A substantial pathway of nicotine metabolism. Author(s): Hecht SS, Hatsukami DK, Bonilla LE, Hochalter JB. Source: Chemical Research in Toxicology. 1999 February; 12(2): 172-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10027795&dopt=Abstract
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Quantitative EEG effects of nicotine replacement by cigarette smoking. Author(s): Newton TF, Cook IA, Holschneider DP, Rosenblatt MR, Lindholm JE, Jarvik MM. Source: Neuropsychobiology. 1998; 37(2): 112-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9566277&dopt=Abstract
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Quitting chew: results from a randomized trial using nicotine patches. Author(s): Howard-Pitney B, Killen JD, Fortmann SP. Source: Experimental and Clinical Psychopharmacology. 1999 November; 7(4): 362-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10609971&dopt=Abstract
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Quitting cigarette smoking produces minimal loss of chronic tolerance to nicotine. Author(s): Perkins KA, Gerlach D, Broge M, Sanders M, Grobe J, Fonte C, Cherry C, Wilson A, Jacob R. Source: Psychopharmacology. 2001 October; 158(1): 7-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11685379&dopt=Abstract
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Randomised trial investigating effect of a novel nicotine delivery device (Eclipse) and a nicotine oral inhaler on smoking behaviour, nicotine and carbon monoxide exposure, and motivation to quit. Author(s): Fagerstrom KO, Hughes JR, Rasmussen T, Callas PW. Source: Tobacco Control. 2000 September; 9(3): 327-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10982578&dopt=Abstract
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Randomized comparative trial of nicotine polacrilex, a transdermal patch, nasal spray, and an inhaler. Author(s): Hajek P, West R, Foulds J, Nilsson F, Burrows S, Meadow A. Source: Archives of Internal Medicine. 1999 September 27; 159(17): 2033-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10510989&dopt=Abstract
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Randomized trial of acupuncture for nicotine withdrawal symptoms. Author(s): White AR, Resch KL, Ernst E. Source: Archives of Internal Medicine. 1998 November 9; 158(20): 2251-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9818805&dopt=Abstract
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Randomized, double-blind, placebo-controlled study of transdermal nicotine patch for smoking cessation. Author(s): Perng RP, Hsieh WC, Chen YM, Lu CC, Chiang SJ. Source: J Formos Med Assoc. 1998 August; 97(8): 547-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9747065&dopt=Abstract
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Rapid Akt activation by nicotine and a tobacco carcinogen modulates the phenotype of normal human airway epithelial cells. Author(s): West KA, Brognard J, Clark AS, Linnoila IR, Yang X, Swain SM, Harris C, Belinsky S, Dennis PA. Source: The Journal of Clinical Investigation. 2003 January; 111(1): 81-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12511591&dopt=Abstract
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Rapid and sensitive high-performance liquid chromatographic determination of nicotine and cotinine in nonsmoker human and rat urines. Author(s): Oddoze C, Pauli AM, Pastor J. Source: J Chromatogr B Biomed Sci Appl. 1998 April 24; 708(1-2): 95-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9653951&dopt=Abstract
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Rapid method for the simultaneous measurement of nicotine and cotinine in urine and serum by gas chromatography-mass spectrometry. Author(s): James H, Tizabi Y, Taylor R. Source: J Chromatogr B Biomed Sci Appl. 1998 April 24; 708(1-2): 87-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9653950&dopt=Abstract
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Rationale for cigarette smoking and for mentholation preference in cocaine- and nicotine-dependent outpatients. Author(s): Wiseman EJ, McMillan DE. Source: Comprehensive Psychiatry. 1998 November-December; 39(6): 358-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9829143&dopt=Abstract
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Rationale for treating pregnant smokers with nicotine patches. Author(s): Scalera A, Koren G. Source: Can Fam Physician. 1998 August; 44: 1601-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9721411&dopt=Abstract
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Re: Cost-effectiveness of the nicotine transdermal patch. Author(s): Stapleton J. Source: Preventive Medicine. 1998 March-April; 27(2): 304-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9579011&dopt=Abstract
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Real-world efficacy of prescription and over-the-counter nicotine replacement therapy. Author(s): Shiffman S, Rolf CN, Hellebusch SJ, Gorsline J, Gorodetzky CW, Chiang YK, Schleusener DS, Di Marino ME. Source: Addiction (Abingdon, England). 2002 May; 97(5): 505-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12033652&dopt=Abstract
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Receptor-mediated action of nicotine in human skin. Author(s): Grando SA. Source: International Journal of Dermatology. 2001 November; 40(11): 691-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11737434&dopt=Abstract
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Receptor-mediated inhibition of keratinocyte migration by nicotine involves modulations of calcium influx and intracellular concentration. Author(s): Zia S, Ndoye A, Lee TX, Webber RJ, Grando SA. Source: The Journal of Pharmacology and Experimental Therapeutics. 2000 June; 293(3): 973-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10869400&dopt=Abstract
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Recommendations for the treatment of nicotine dependency. Author(s): Montalto NJ. Source: J Am Osteopath Assoc. 2002 June; 102(6): 342-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12090652&dopt=Abstract
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Reducing toxicity exposure for the nicotine-dependent. Author(s): Sweanor D. Source: Addiction (Abingdon, England). 2003 September; 98(9): 1197-8; Discussion 12047. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12930203&dopt=Abstract
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Reduction of tobacco withdrawal symptoms with a sublingual nicotine tablet: a placebo controlled study. Author(s): Molander L, Lunell E, Fagerstrom KO. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2000 May; 2(2): 187-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11072457&dopt=Abstract
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Reference interval and subject variation in excretion of urinary metabolites of nicotine from non-smoking healthy subjects in Denmark. Author(s): Hansen AM, Garde AH, Christensen JM, Eller N, Knudsen LE, HeinrichRamm R. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 2001 February; 304(1-2): 125-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11165207&dopt=Abstract
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Regional and cellular induction of nicotine-metabolizing CYP2B1 in rat brain by chronic nicotine treatment. Author(s): Miksys S, Hoffmann E, Tyndale RF. Source: Biochemical Pharmacology. 2000 June 15; 59(12): 1501-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10799646&dopt=Abstract
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Regional cerebral blood flow effects of nicotine in overnight abstinent smokers. Author(s): Zubieta J, Lombardi U, Minoshima S, Guthrie S, Ni L, Ohl LE, Koeppe RA, Domino EF. Source: Biological Psychiatry. 2001 June 1; 49(11): 906-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11377408&dopt=Abstract
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Regulation of cytokine production in human gingival fibroblasts following treatment with nicotine and lipopolysaccharide. Author(s): Wendell KJ, Stein SH. Source: J Periodontol. 2001 August; 72(8): 1038-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11525435&dopt=Abstract
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Regulation of feeding-associated peptides and receptors by nicotine. Author(s): Li MD, Parker SL, Kane JK. Source: Molecular Neurobiology. 2000 August-December; 22(1-3): 143-65. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11414277&dopt=Abstract
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Regulation of nicotine replacement therapies (NRT): a critique of current practice. Author(s): McNeill A, Foulds J, Bates C. Source: Addiction (Abingdon, England). 2001 December; 96(12): 1757-68. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11784468&dopt=Abstract
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Regulation of nicotinic acetylcholine receptor numbers and function by chronic nicotine exposure. Author(s): Gentry CL, Lukas RJ. Source: Current Drug Targets. Cns and Neurological Disorders. 2002 August; 1(4): 35985. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12769610&dopt=Abstract
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Regulatory imbalance between medicinal and non-medicinal nicotine. Author(s): Sweanor D. Source: Addiction (Abingdon, England). 2000 January; 95 Suppl 1: S25-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10723819&dopt=Abstract
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Reinforcing effects of nicotine as a function of smoking status. Author(s): Perkins KA, Gerlach D, Broge M, Fonte C, Wilson A. Source: Experimental and Clinical Psychopharmacology. 2001 August; 9(3): 243-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11534534&dopt=Abstract
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Relationship between interindividual differences in nicotine metabolism and CYP2A6 genetic polymorphism in humans. Author(s): Nakajima M, Kwon JT, Tanaka N, Zenta T, Yamamoto Y, Yamamoto H, Yamazaki H, Yamamoto T, Kuroiwa Y, Yokoi T. Source: Clinical Pharmacology and Therapeutics. 2001 January; 69(1): 72-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11180041&dopt=Abstract
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Relationship between mood improvement and sleep changes with acute nicotine administration in non-smoking major depressed patients. Author(s): Salin-Pascual RJ. Source: Revista De Investigacion Clinica; Organo Del Hospital De Enfermedades De La Nutricion. 2002 January-February; 54(1): 36-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11995405&dopt=Abstract
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Relationship of ADHD, depression, and non-tobacco substance use disorders to nicotine dependence in substance-dependent delinquents. Author(s): Riggs PD, Mikulich SK, Whitmore EA, Crowley TJ. Source: Drug and Alcohol Dependence. 1999 May 3; 54(3): 195-205. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10372793&dopt=Abstract
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Relationships between sensation seeking and emotional symptomatology during smoking cessation with nicotine patch therapy. Author(s): Carton S, Le Houezec J, Lagrue G, Jouvent R. Source: Addictive Behaviors. 2000 September-October; 25(5): 653-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11023009&dopt=Abstract
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Reliability of selected measures of nicotine dependence among adolescents. Author(s): O'Loughlin J, Tarasuk J, Difranza J, Paradis G. Source: Annals of Epidemiology. 2002 July; 12(5): 353-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12062924&dopt=Abstract
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Religious faith and nicotine cessation. Author(s): Neumann JK, Peeples B. Source: Military Medicine. 2001 May; 166(5): V. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11370215&dopt=Abstract
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Research into smoking or nicotine and human cognitive performance: does the source of funding make a difference? Author(s): Turner C, Spilich GJ. Source: Addiction (Abingdon, England). 1997 November; 92(11): 1423-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9519485&dopt=Abstract
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Respiratory suppression induced by nicotine withdrawal in the neonatal rat brainstem: implications in the SIDS risk factor. Author(s): Okada Y, Kuwana S, Iwanami M. Source: Advances in Experimental Medicine and Biology. 2001; 499: 187-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11729876&dopt=Abstract
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Response to nicotine dependence treatment in smokers with current and past alcohol problems. Author(s): Hays JT, Schroeder DR, Offord KP, Croghan IT, Patten CA, Hurt RD, Jorenby DE, Fiore MC. Source: Annals of Behavioral Medicine : a Publication of the Society of Behavioral Medicine. 1999 Summer; 21(3): 244-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10626032&dopt=Abstract
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Review of the evidence that pH is a determinant of nicotine dosage from oral use of smokeless tobacco. Author(s): Tomar SL, Henningfield JE. Source: Tobacco Control. 1997 Autumn; 6(3): 219-25. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9396107&dopt=Abstract
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Risk of acute first myocardial infarction and use of nicotine patches in a general population. Author(s): Kimmel SE, Berlin JA, Miles C, Jaskowiak J, Carson JL, Strom BL. Source: Journal of the American College of Cardiology. 2001 April; 37(5): 1297-302. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11300438&dopt=Abstract
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Risks and benefits of nicotine to aid smoking cessation in pregnancy. Author(s): Dempsey DA, Benowitz NL. Source: Drug Safety : an International Journal of Medical Toxicology and Drug Experience. 2001; 24(4): 277-322. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11330657&dopt=Abstract
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Role of alpha7 nicotinic receptors in nicotine dependence and implications for psychiatric illness. Author(s): Nomikos GG, Schilstrom B, Hildebrand BE, Panagis G, Grenhoff J, Svensson TH. Source: Behavioural Brain Research. 2000 August; 113(1-2): 97-103. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10942036&dopt=Abstract
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Role of dopamine in the behavioural actions of nicotine related to addiction. Author(s): Di Chiara G. Source: European Journal of Pharmacology. 2000 March 30; 393(1-3): 295-314. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10771025&dopt=Abstract
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Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Author(s): Yamazaki H, Inoue K, Hashimoto M, Shimada T. Source: Archives of Toxicology. 1999 March; 73(2): 65-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10350185&dopt=Abstract
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Safety of nicotine in smokers with hypertension. Author(s): Benowitz NL. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 2001 July; 14(7 Pt 1): 731-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11465662&dopt=Abstract
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Self-reported smoking habits, biochemical markers, and nicotine dependence in a sample of the Danish population. Author(s): Seersholm N, Nielsen NH, Tonnesen P. Source: J R Soc Health. 1999 June; 119(2): 92-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11043002&dopt=Abstract
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Sensation seeking, puberty, and nicotine, alcohol, and marijuana use in adolescence. Author(s): Martin CA, Kelly TH, Rayens MK, Brogli BR, Brenzel A, Smith WJ, Omar HA. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2002 December; 41(12): 1495-502. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12447037&dopt=Abstract
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Sensitive and simple method for the determination of nicotine and cotinine in human urine, plasma and saliva by gas chromatography-mass spectrometry. Author(s): Shin HS, Kim JG, Shin YJ, Jee SH. Source: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences. 2002 March 25; 769(1): 177-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11936690&dopt=Abstract
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Sensitivity of nicotine-containing and de-nicotinized cigarette consumption to alternative non-drug reinforcement: a behavioral economic analysis. Author(s): Shahan TA, Bickel WK, Badger GJ, Giordano LA. Source: Behavioural Pharmacology. 2001 July; 12(4): 277-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11548113&dopt=Abstract
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Sex differences in nicotine effects and self-administration: review of human and animal evidence. Author(s): Perkins KA, Donny E, Caggiula AR. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 1999 December; 1(4): 301-15. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11072427&dopt=Abstract
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Sex differences in the subjective and reinforcing effects of cigarette nicotine dose. Author(s): Perkins KA, Jacobs L, Sanders M, Caggiula AR. Source: Psychopharmacology. 2002 September; 163(2): 194-201. Epub 2002 July 13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12202966&dopt=Abstract
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Should the FDA regulate nicotine-containing cigarettes? Has the Agency established a legal basis and, if not, should congress grant it? Author(s): Carchman SH. Source: Food Drug Law J. 1996; 51(1): 85-138. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11794355&dopt=Abstract
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Should we recommend nicotine replacement therapy? Author(s): David SP. Source: American Family Physician. 2001 June 1; 63(11): 2245-7. Erratum In: Am Fam Physician 2002 February 15; 65(4): 560. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11417777&dopt=Abstract
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Simultaneous analysis of nicotine, nicotine metabolites, and tobacco alkaloids in serum or urine by tandem mass spectrometry, with clinically relevant metabolic profiles. Author(s): Moyer TP, Charlson JR, Enger RJ, Dale LC, Ebbert JO, Schroeder DR, Hurt RD. Source: Clinical Chemistry. 2002 September; 48(9): 1460-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12194923&dopt=Abstract
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Simultaneous determination of mecamylamine, nicotine, and cotinine in plasma by gas chromatography-mass spectrometry. Author(s): Jacob P 3rd, Wu S, Yu L, Benowitz NL. Source: Journal of Pharmaceutical and Biomedical Analysis. 2000 September; 23(4): 65361. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10975241&dopt=Abstract
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Simultaneous determination of the tobacco smoke uptake parameters nicotine, cotinine and thiocyanate in urine, saliva and hair, using gas chromatography-mass spectrometry for characterisation of smoking status of recently exposed subjects. Author(s): Torano JS, van Kan HJ. Source: The Analyst. 2003 July; 128(7): 838-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12894819&dopt=Abstract
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Slower metabolism and reduced intake of nicotine from cigarette smoking in Chinese-Americans. Author(s): Benowitz NL, Perez-Stable EJ, Herrera B, Jacob P 3rd. Source: Journal of the National Cancer Institute. 2002 January 16; 94(2): 108-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11792749&dopt=Abstract
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Smoke free hospitals: withdrawal from cigarettes should not be confused with withdrawal from nicotine. Author(s): McKee M, Gilmore A, Novotny T. Source: Bmj (Clinical Research Ed.). 2003 October 4; 327(7418): 811. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14525898&dopt=Abstract
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Smokeless tobacco: harm reduction or nicotine overload? Author(s): Vainio H, Weiderpass E. Source: European Journal of Cancer Prevention : the Official Journal of the European Cancer Prevention Organisation (Ecp). 2003 April; 12(2): 89-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12671531&dopt=Abstract
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Smoking after nicotine deprivation enhances cognitive performance and decreases tobacco craving in drug abusers. Author(s): Bell SL, Taylor RC, Singleton EG, Henningfield JE, Heishman SJ. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 1999 March; 1(1): 45-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11072387&dopt=Abstract
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Smoking and balance: correlation of nicotine-induced nystagmus and postural body sway. Author(s): Pereira CB, Strupp M, Holzleitner T, Brandt T. Source: Neuroreport. 2001 May 8; 12(6): 1223-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11338195&dopt=Abstract
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Smoking and quitting with the aid of nicotine replacement therapies in the English adult population. Results from the Health Education Monitoring Survey 1995. Author(s): Buck D, Morgan A. Source: European Journal of Public Health. 2001 June; 11(2): 211-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11420814&dopt=Abstract
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Smoking cessation in adolescents: the role of nicotine dependence, stress, and coping methods. Author(s): Siqueira LM, Rolnitzky LM, Rickert VI. Source: Archives of Pediatrics & Adolescent Medicine. 2001 April; 155(4): 489-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11296077&dopt=Abstract
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Smoking cessation in the workplace: results of an intervention programme using nicotine patches. Author(s): Cruse SM, Forster NJ, Thurgood G, Sys L. Source: Occupational Medicine (Oxford, England). 2001 December; 51(8): 501-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11741082&dopt=Abstract
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Smoking cessation with four nicotine replacement regimes in a lung clinic. Author(s): Tonnesen P, Mikkelsen KL. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2000 October; 16(4): 717-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11106218&dopt=Abstract
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Smoking cessation with nicotine replacement therapy among health care workers: randomized double-blind study. Author(s): Glavas D, Rumboldt M, Rumboldt Z. Source: Croatian Medical Journal. 2003 April; 44(2): 219-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12698515&dopt=Abstract
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Smoking cessation, smoking reduction, and delayed quitting among smokers given nicotine patches and a self-help pamphlet. Author(s): Jolicoeur DG, Richter KP, Ahluwalia JS, Mosier MC, Resnicow K. Source: Substance Abuse : Official Publication of the Association for Medical Education and Research in Substance Abuse. 2003 June; 24(2): 101-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12766377&dopt=Abstract
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Smoking for nicotine. Author(s): Johnson EW. Source: American Journal of Physical Medicine & Rehabilitation / Association of Academic Physiatrists. 2001 August; 80(8): 559. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11475473&dopt=Abstract
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Smoking history and nicotine effects on cognitive performance. Author(s): Ernst M, Heishman SJ, Spurgeon L, London ED. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2001 September; 25(3): 313-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11522460&dopt=Abstract
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Smoking reduction in smokers compliant to a smoking cessation trial with nicotine patch. Author(s): Fornai E, Desideri M, Pistelli F, Carrozzi L, Puntoni R, Avino S, Gustavsson G, Sawe U, Viegi G, Giuntini C. Source: Monaldi Arch Chest Dis. 2001 February; 56(1): 5-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11407211&dopt=Abstract
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Smoking reduction with oral nicotine inhalers: double blind, randomised clinical trial of efficacy and safety. Author(s): Bolliger CT, Zellweger JP, Danielsson T, van Biljon X, Robidou A, Westin A, Perruchoud AP, Sawe U. Source: Bmj (Clinical Research Ed.). 2000 August 5; 321(7257): 329-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10926587&dopt=Abstract
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Smoking, anxiety, and attention: support for the role of nicotine in attentionally mediated anxiolysis. Author(s): Kassel JD, Unrod M. Source: Journal of Abnormal Psychology. 2000 February; 109(1): 161-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10740949&dopt=Abstract
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Smoking, nicotine and tar and risk of small for gestational age babies. Author(s): Mitchell EA, Thompson JM, Robinson E, Wild CJ, Becroft DM, Clark PM, Glavish N, Pattison NS, Pryor JE. Source: Acta Paediatrica (Oslo, Norway : 1992). 2002; 91(3): 323-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12022307&dopt=Abstract
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Smoking, nicotine and thrombotic risk--a role for platelet dependent thrombin generation? Author(s): Hjemdahl P. Source: European Heart Journal. 2001 January; 22(1): 16-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11133205&dopt=Abstract
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Specific sensory detection, discrimination, and hedonic estimation of nicotine enantiomers in smokers and nonsmokers: are there limitations in replacing the sensory components of nicotine? Author(s): Thuerauf N, Kaegler M, Renner B, Barocka A, Kobal G. Source: Journal of Clinical Psychopharmacology. 2000 August; 20(4): 472-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10917409&dopt=Abstract
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Subjective effects of the nicotine lozenge: assessment of abuse liability. Author(s): Houtsmuller EJ, Henningfield JE, Stitzer ML. Source: Psychopharmacology. 2003 April; 167(1): 20-7. Epub 2003 March 04. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12616334&dopt=Abstract
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Subjective responses to nicotine in smokers may be associated with responses to caffeine and to alcohol. Author(s): Perkins KA, Fonte C, Ashcom J, Broge M, Wilson A. Source: Experimental and Clinical Psychopharmacology. 2001 February; 9(1): 91-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11519639&dopt=Abstract
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Symposium overview: mechanism of action of nicotine on neuronal acetylcholine receptors, from molecule to behavior. Author(s): Narahashi T, Fenster CP, Quick MW, Lester RA, Marszalec W, Aistrup GL, Sattelle DB, Martin BR, Levin ED. Source: Toxicological Sciences : an Official Journal of the Society of Toxicology. 2000 October; 57(2): 193-202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11006350&dopt=Abstract
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Symptoms of nicotine dependence and other predictors of student smoking at school: implications for school smoking policy. Author(s): Soteriades ES, DiFranza JR, Savageau JA, Nicolaou M. Source: The Journal of School Health. 2003 April; 73(4): 154-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12728614&dopt=Abstract
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Synaptic plasticity and nicotine addiction. Author(s): Dani JA, Ji D, Zhou FM. Source: Neuron. 2001 August 16; 31(3): 349-52. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11516393&dopt=Abstract
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Synergistic effects of nicotine on arecoline-induced cytotoxicity in human buccal mucosal fibroblasts. Author(s): Chang YC, Hu CC, Tseng TH, Tai KW, Lii CK, Chou MY. Source: Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 2001 September; 30(8): 458-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11545236&dopt=Abstract
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Systemic and renal effect of nicotine in non-smokers: influence of vitamin C. Author(s): Halimi JM, Mimran A. Source: Journal of Hypertension. 2000 November; 18(11): 1665-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11081781&dopt=Abstract
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Systemic nicotine exposure in tobacco harvesters. Author(s): D'Alessandro A, Benowitz NL, Muzi G, Eisner MD, Filiberto S, Fantozzi P, Montanari L, Abbritti G. Source: Archives of Environmental Health. 2001 May-June; 56(3): 257-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11480503&dopt=Abstract
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Systemic nicotine stimulates human adipose tissue lipolysis through local cholinergic and catecholaminergic receptors. Author(s): Andersson K, Arner P. Source: International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity. 2001 August; 25(8): 1225-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11477508&dopt=Abstract
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Tetrodotoxin-sensitive enhancement of inhibition in CA1 pyramidal neurones by nicotine. Author(s): Hulo S, Muller D. Source: Neuroreport. 2001 May 25; 12(7): 1351-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11388409&dopt=Abstract
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The association between degree of nicotine dependence and other health behaviours. Findings from a German general population study. Author(s): Schumann A, Hapke U, Rumpf HJ, Meyer C, John U. Source: European Journal of Public Health. 2001 December; 11(4): 450-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11766489&dopt=Abstract
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The association between high nicotine dependence and severe mental illness may be consistent across countries. Author(s): de Leon J, Becona E, Gurpegui M, Gonzalez-Pinto A, Diaz FJ. Source: The Journal of Clinical Psychiatry. 2002 September; 63(9): 812-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12363123&dopt=Abstract
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The association of testosterone with nicotine use in young adult females. Author(s): Martin CA, Logan TK, Portis C, Leukefeld CG, Lynam D, Staton M, Brogli B, Flory K, Clayton RR. Source: Addictive Behaviors. 2001 March-April; 26(2): 279-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11316383&dopt=Abstract
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The biology of nicotine dependence: from the 1988 Surgeon General's Report to the present and into the future. Author(s): Benowitz NL. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 1999; 1 Suppl 2: S159-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11768175&dopt=Abstract
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The clinical effectiveness and cost-effectiveness of bupropion and nicotine replacement therapy for smoking cessation: a systematic review and economic evaluation. Author(s): Woolacott NF, Jones L, Forbes CA, Mather LC, Sowden AJ, Song FJ, Raftery JP, Aveyard PN, Hyde CJ, Barton PM. Source: Health Technology Assessment (Winchester, England). 2002; 6(16): 1-245. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12269277&dopt=Abstract
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The demand for nicotine replacement therapies. Author(s): Tauras JA, Chaloupka FJ. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2003 April; 5(2): 237-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745497&dopt=Abstract
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The discriminative stimulus and reinforcing effects of nicotine in humans following nicotine pretreatment. Author(s): Perkins KA, Fonte C, Meeker J, White W, Wilson A. Source: Behavioural Pharmacology. 2001 February; 12(1): 35-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11270510&dopt=Abstract
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The effects of extrinsic context on nicotine discrimination. Author(s): Duka T, Seiss E, Tasker R. Source: Behavioural Pharmacology. 2002 February; 13(1): 39-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11990718&dopt=Abstract
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The effects of transdermal nicotine therapy for smoking cessation on depressive symptoms in patients with major depression. Author(s): Thorsteinsson HS, Gillin JC, Patten CA, Golshan S, Sutton LD, Drummond S, Clark CP, Kelsoe J, Rapaport M. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2001 April; 24(4): 350-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11182530&dopt=Abstract
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The efficacy of computer-tailored smoking cessation material as a supplement to nicotine patch therapy. Author(s): Shiffman S, Paty JA, Rohay JM, Di Marino ME, Gitchell JG. Source: Drug and Alcohol Dependence. 2001 September 1; 64(1): 35-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11470339&dopt=Abstract
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The hardest thing is the habit: a qualitative investigation of adolescent smokers' experience of nicotine dependence. Author(s): O'Loughlin J, Kishchuk N, DiFranza J, Tremblay M, Paradis G. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2002 May; 4(2): 201-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12028853&dopt=Abstract
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The heritability of failed smoking cessation and nicotine withdrawal in twins who smoked and attempted to quit. Author(s): Xian H, Scherrer JF, Madden PA, Lyons MJ, Tsuang M, True WR, Eisen SA. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2003 April; 5(2): 245-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745498&dopt=Abstract
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The influence of personality on nicotine craving: a hierarchical multivariate statistical prediction model. Author(s): Reuter M, Netter P. Source: Neuropsychobiology. 2001; 44(1): 47-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11408793&dopt=Abstract
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The influence of pH and nicotine concentration in oral moist snuff on mucosal changes and salivary pH in Swedish snuff users. Author(s): Andersson G, Warfvinge G. Source: Swed Dent J. 2003; 27(2): 67-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12856395&dopt=Abstract
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The need for dissemination of evidence-based results from research on nicotine and tobacco. Author(s): Swan GE. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2003 February; 5(1): 7-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745501&dopt=Abstract
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The origin of a nicotine detection method. Author(s): Ogden MW. Source: Aihaj : a Journal for the Science of Occupational and Environmental Health and Safety. 2001 November-December; 62(6): 665-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11767927&dopt=Abstract
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The potential role of cotinine in the cognitive and neuroprotective actions of nicotine. Author(s): Buccafusco JJ, Terry AV Jr. Source: Life Sciences. 2003 May 16; 72(26): 2931-42. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12706481&dopt=Abstract
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The relative buffering capacities of saliva and moist snuff: implications for nicotine absorption. Author(s): Ciolino LA, McCauley HA, Fraser DB, Wolnik KA. Source: Journal of Analytical Toxicology. 2001 January-February; 25(1): 15-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11215994&dopt=Abstract
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The role of nitric oxide in cigarette smoking and nicotine addiction. Author(s): Vleeming W, Rambali B, Opperhuizen A. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2002 August; 4(3): 341-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12215243&dopt=Abstract
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The Society for Research in Nicotine and Tobacco--an amazing success story. Author(s): West R. Source: Addiction (Abingdon, England). 2001 December; 96(12): 1867. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11791540&dopt=Abstract
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The use of nicotine in dermatology revisited. Author(s): Burkhart CG, Burkhart CN. Source: International Journal of Dermatology. 2001 November; 40(11): 731-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11737446&dopt=Abstract
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The use of nicotine replacement therapy during hospitalization. Author(s): Emmons KM, Goldstein MG, Roberts M, Cargill B, Sherman CB, Millman R, Brown R, Abrams DB. Source: Annals of Behavioral Medicine : a Publication of the Society of Behavioral Medicine. 2000 Fall; 22(4): 325-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11253444&dopt=Abstract
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The vagus nerve, macrophages, and nicotine. Author(s): Floto RA, Smith KG. Source: Lancet. 2003 March 29; 361(9363): 1069-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12672307&dopt=Abstract
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The war against nicotine and tobacco: new tools? Author(s): Cerny T. Source: Onkologie. 2002 October; 25(5): 404. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12472104&dopt=Abstract
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Threshold doses for nicotine discrimination in smokers and non-smokers. Author(s): Perkins KA, Fonte C, Sanders M, Meeker J, Wilson A. Source: Psychopharmacology. 2001 May; 155(2): 163-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11401005&dopt=Abstract
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Tobacco smoking, nicotine, and nicotine and non-nicotine replacement therapies. Author(s): Frishman WH, Ky T, Ismail A. Source: Heart Disease. 2001 November-December; 3(6): 365-77. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11975821&dopt=Abstract
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Tobacco use outcomes among patients with lung cancer treated for nicotine dependence. Author(s): Sanderson Cox L, Patten CA, Ebbert JO, Drews AA, Croghan GA, Clark MM, Wolter TD, Decker PA, Hurt RD. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 August 15; 20(16): 3461-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12177107&dopt=Abstract
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Tobacco use outcomes of adolescents treated clinically for nicotine dependence. Author(s): Patten CA, Ames SC, Ebbert JO, Wolter TD, Hurt RD, Gauvin TR. Source: Archives of Pediatrics & Adolescent Medicine. 2001 July; 155(7): 831-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11434853&dopt=Abstract
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Toenail nicotine levels as a biomarker of tobacco smoke exposure. Author(s): Al-Delaimy WK, Mahoney GN, Speizer FE, Willett WC. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 2002 November; 11(11): 1400-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12433718&dopt=Abstract
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Tolerability of concurrent use of nicotine gum and smoking in healthy volunteers. Author(s): Stahl MM, Wohlfart B, Pahlm O. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2001 May; 3(2): 157-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11403730&dopt=Abstract
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Tolerance to repeated nicotine administration on performance, subjective, and physiological responses in nonsmokers. Author(s): Heishman SJ, Henningfield JE. Source: Psychopharmacology. 2000 October; 152(3): 321-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11105943&dopt=Abstract
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Transdermal nicotine for agitation in dementia. Author(s): Rosin RA, Levine MD, Peskind E. Source: The American Journal of Geriatric Psychiatry : Official Journal of the American Association for Geriatric Psychiatry. 2001 Fall; 9(4): 443-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11739072&dopt=Abstract
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Transdermal nicotine in PD: a randomized, double-blind, placebo-controlled study. Author(s): Allam MF. Source: Neurology. 2002 April 9; 58(7): 1133; Author Reply 1133. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11940713&dopt=Abstract
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Transdermal nicotine patches do not cause clinically significant gastroesophageal reflux or esophageal motor disorders. Author(s): Wright RA, Goldsmith LJ, Ameen V, D'Angelo A, Kirby SL, Prakash S. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 1999 December; 1(4): 371-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11072435&dopt=Abstract
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Transport mechanisms of nicotine across the human intestinal epithelial cell line Caco-2. Author(s): Fukada A, Saito H, Inui K. Source: The Journal of Pharmacology and Experimental Therapeutics. 2002 August; 302(2): 532-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12130712&dopt=Abstract
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Treating nicotine addiction: not a medical problem? Author(s): Britton J, Jarvis M, McNeill A, Bates C, Cuthbertson L, Godfrey C. Source: American Journal of Respiratory and Critical Care Medicine. 2001 July 1; 164(1): 13-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11435233&dopt=Abstract
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Treating nicotine dependence during pregnancy and postpartum: understanding clinician knowledge and performance. Author(s): Bonollo DP, Zapka JG, Stoddard AM, Ma Y, Pbert L, Ockene JK. Source: Patient Education and Counseling. 2002 December; 48(3): 265-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12477611&dopt=Abstract
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Treating nicotine dependence. Author(s): Glover ED, Glover PN. Source: W V Med J. 2001 January-February; 97(1): 39-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11257836&dopt=Abstract
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Treatment of nicotine dependence. Author(s): Dale LC, Ebbert JO, Hays JT, Hurt RD. Source: Mayo Clinic Proceedings. 2000 December; 75(12): 1311-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11126841&dopt=Abstract
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Ulcerative colitis responsive to smoking and to nicotine chewing gum in a patient with alpha 1 anti-trypsin deficiency. Author(s): Watson JP, Lewis RA. Source: Respiratory Medicine. 1995 October; 89(9): 635-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7494920&dopt=Abstract
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Up-regulation of epidermal growth factor-receptors (EGF-R) by nicotine in cervical cancer cell lines: this effect may be mediated by EGF. Author(s): Mathur RS, Mathur SP, Young RC. Source: American Journal of Reproductive Immunology (New York, N.Y. : 1989). 2000 August; 44(2): 114-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10994639&dopt=Abstract
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Uptake of nicotine in hair during controlled environmental air exposure to nicotine vapour: evidence for a major contribution of environmental nicotine to the overall nicotine found in hair from smokers and non-smokers. Author(s): Nilsen T, Zahlsen K, Nilsen OG. Source: Pharmacology & Toxicology. 1994 September-October; 75(3-4): 136-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7800653&dopt=Abstract
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Urinary nicotine metabolite excretion and lung cancer risk in a female cohort. Author(s): Ellard GA, de Waard F, Kemmeren JM. Source: British Journal of Cancer. 1995 September; 72(3): 788-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7669596&dopt=Abstract
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Urticarial reaction following the inhalation of nicotine in tobacco smoke. Author(s): Lee IW, Ahn SK, Choi EH, Lee SH. Source: The British Journal of Dermatology. 1998 March; 138(3): 486-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9580805&dopt=Abstract
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Usage patterns of transdermal nicotine when purchased as a non-prescription medicine from pharmacies. Author(s): Shaw JP, Ferry DG, Pethica D, Brenner D, Tucker IG. Source: Tobacco Control. 1998 Summer; 7(2): 161-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9789935&dopt=Abstract
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Use and effectiveness of transdermal nicotine in primary care settings. Author(s): White DR. Source: Archives of Family Medicine. 1995 April; 4(4): 304. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7711911&dopt=Abstract
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Use and effectiveness of transdermal nicotine in primary care settings. Author(s): Cummings KM, Biernbaum RM, Zevon MA, Deloughry T, Jaen CR. Source: Archives of Family Medicine. 1994 August; 3(8): 682-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7952254&dopt=Abstract
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Use of carbon-11 nicotine in PET studies. Author(s): Lundqvist H, Langstrom B, Nordberg A. Source: European Journal of Nuclear Medicine. 1997 July; 24(7): 825-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9289404&dopt=Abstract
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Use of nicotine replacement therapy in adolescent smokers and nonsmokers. Author(s): Klesges LM, Johnson KC, Somes G, Zbikowski S, Robinson L. Source: Archives of Pediatrics & Adolescent Medicine. 2003 June; 157(6): 517-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12796230&dopt=Abstract
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Use of over-the-counter nicotine patch for smoking cessation: prudent or premature? Author(s): McNagny SE, Ahluwalia JS. Source: Jama : the Journal of the American Medical Association. 1996 August 7; 276(5): 371-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8683812&dopt=Abstract
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Use of the fagerstrom tolerance questionnaire for measuring nicotine dependence among adolescent smokers in China: a pilot test. Author(s): Chen X, Zheng H, Steve S, Gong J, Stacy A, Xia J, Gallaher P, Dent C, Azen S, Shan J, Unger JB, Johnson CA. Source: Psychology of Addictive Behaviors : Journal of the Society of Psychologists in Addictive Behaviors. 2002 September; 16(3): 260-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12236462&dopt=Abstract
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Use of the nicotine patch by pregnant women. Author(s): Hackman R, Kapur B, Koren G. Source: The New England Journal of Medicine. 1999 November 25; 341(22): 1700. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10610440&dopt=Abstract
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Use of the nicotine skin patch by smokers in 20 communities in the United States, 1992-1993. Author(s): Cummings KM, Hyland A, Ockene JK, Hymowitz N, Manley M. Source: Tobacco Control. 1997; 6 Suppl 2: S63-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9583655&dopt=Abstract
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Use of transdermal nicotine systems in a possible suicide attempt. Author(s): Montalto N, Brackett CC, Sobol T. Source: The Journal of the American Board of Family Practice / American Board of Family Practice. 1994 September-October; 7(5): 417-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7810357&dopt=Abstract
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Using nicotine measurements and parental reports to assess indoor air: the PIAMA birth cohort study. Prevention and Incidence of Asthma and Mite Allergy. Author(s): Brunekreef B, Leaderer BP, van Strien R, Oldenwening M, Smit HA, Koopman L, Kerkhof M. Source: Epidemiology (Cambridge, Mass.). 2000 May; 11(3): 350-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10784258&dopt=Abstract
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Using nicotine replacement therapy in treating nicotine addiction in adolescents. Author(s): Maharaj K, Ternullo S. Source: J Sch Nurs. 2001 October; 17(5): 278-82. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11885345&dopt=Abstract
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Using qualitative research to inform survey development on nicotine dependence among adolescents. Author(s): Nichter M, Nichter M, Thompson PJ, Shiffman S, Moscicki AB. Source: Drug and Alcohol Dependence. 2002 November; 68 Suppl 1: S41-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12324174&dopt=Abstract
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Using the nicotine patch to stop smoking. Author(s): Richardson GS. Source: Jama : the Journal of the American Medical Association. 1995 January 18; 273(3): 181; Author Reply 182. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7880259&dopt=Abstract
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Using the nicotine patch to stop smoking. Author(s): Haxby D, Toffler WL. Source: Jama : the Journal of the American Medical Association. 1995 January 18; 273(3): 181-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7807644&dopt=Abstract
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Using the nicotine patch to stop smoking. Author(s): Swartz SH. Source: Jama : the Journal of the American Medical Association. 1995 January 18; 273(3): 181; Author Reply 182. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7807643&dopt=Abstract
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Utilization of nicotine nasal spray in smoking cessation. Author(s): Montalto NJ, Garrett SD. Source: J Am Osteopath Assoc. 1998 March; 98(3): 160-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9558832&dopt=Abstract
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Vaccines against nicotine: how effective are they likely to be in preventing smoking? Author(s): Vocci FJ, Chiang CN. Source: Cns Drugs. 2001; 15(7): 505-14. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11510621&dopt=Abstract
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Validation of self-reported smoking by analysis of hair for nicotine and cotinine. Author(s): Eliopoulos C, Klein J, Koren G. Source: Therapeutic Drug Monitoring. 1996 October; 18(5): 532-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8885115&dopt=Abstract
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Validity of the Fagerstrom test for nicotine dependence and of the Heaviness of Smoking Index among relatively light smokers. Author(s): Etter JF, Duc TV, Perneger TV. Source: Addiction (Abingdon, England). 1999 February; 94(2): 269-81. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10396794&dopt=Abstract
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Variable CYP2A6-mediated nicotine metabolism alters smoking behavior and risk. Author(s): Tyndale RF, Sellers EM. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2001 April; 29(4 Pt 2): 548-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11259349&dopt=Abstract
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Variation within global cigarette brands in tar, nicotine, and certain nitrosamines: analytic study. Author(s): Gray N, Zaridze D, Robertson C, Krivosheeva L, Sigacheva N, Boyle P. Source: Tobacco Control. 2000 September; 9(3): 351. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11203247&dopt=Abstract
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Varying nicotine patch dose and type of smoking cessation counseling. Author(s): Jorenby DE, Smith SS, Fiore MC, Hurt RD, Offord KP, Croghan IT, Hays JT, Lewis SF, Baker TB. Source: Jama : the Journal of the American Medical Association. 1995 November 1; 274(17): 1347-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7563558&dopt=Abstract
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Vasculitis attributed to the nicotine patch (Nicotinell). Author(s): Van der Klauw MM, Van Hillo B, Van den Berg WH, Bolsius EP, Sutorius FF, Stricker BH. Source: The British Journal of Dermatology. 1996 February; 134(2): 361-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8746358&dopt=Abstract
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Vertical nystagmus in normal subjects: effects of head position, nicotine and scopolamine. Author(s): Kim JI, Somers JT, Stahl JS, Bhidayasiri R, Leigh RJ. Source: Journal of Vestibular Research : Equilibrium & Orientation. 2000; 10(6): 291-300. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11455110&dopt=Abstract
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Vice President Al Gore. Plenary address at Addicted To Nicotine: A National Research Forum July 27-28, 1998, Bethesda, MD. Author(s): Gore A. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 1999; 1 Suppl 2: S13-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11768170&dopt=Abstract
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Weight change after smoking cessation using variable doses of transdermal nicotine replacement. Author(s): Dale LC, Schroeder DR, Wolter TD, Croghan IT, Hurt RD, Offord KP. Source: Journal of General Internal Medicine : Official Journal of the Society for Research and Education in Primary Care Internal Medicine. 1998 January; 13(1): 9-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9462489&dopt=Abstract
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Weight gain and insulin resistance during nicotine replacement therapy. Author(s): Assali AR, Beigel Y, Schreibman R, Shafer Z, Fainaru M. Source: Clin Cardiol. 1999 May; 22(5): 357-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10326169&dopt=Abstract
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What aspects of human performance are truly enhanced by nicotine? Author(s): Heishman SJ. Source: Addiction (Abingdon, England). 1998 March; 93(3): 317-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10328040&dopt=Abstract
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What is the most effective nicotine replacement therapy? Author(s): Diefenbacher LJ, Smith PO, Nashelsky J. Source: The Journal of Family Practice. 2003 June; 52(6): 492-4; Discussion 494. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12791233&dopt=Abstract
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What's new in Nicotine & Tobacco Research? Author(s): Hebert R. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2001 February; 3(1): 3-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11260805&dopt=Abstract
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What's new in Nicotine & Tobacco Research? Author(s): Hebert R. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2000 August; 2(3): 213-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11082820&dopt=Abstract
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What's new in Nicotine & Tobacco Research? Author(s): Hebert R. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2000 November; 2(4): 313-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11197309&dopt=Abstract
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Which smokers are helped to give up smoking using transdermal nicotine patches? Results from a randomized, double-blind, placebo-controlled trial. Author(s): Yudkin PL, Jones L, Lancaster T, Fowler GH. Source: The British Journal of General Practice : the Journal of the Royal College of General Practitioners. 1996 March; 46(404): 145-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8731618&dopt=Abstract
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Who gets what symptom? Effects of psychiatric cofactors and nicotine dependence on patterns of smoking withdrawal symptomatology. Author(s): Pomerleau CS, Marks JL, Pomerleau OF. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2000 August; 2(3): 275-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11082828&dopt=Abstract
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Why Britain needs a nicotine regulation authority. To bring consistency and regulation to tobacco and alternative nicotine products. Author(s): Britton J, McNeill A. Source: Bmj (Clinical Research Ed.). 2001 May 5; 322(7294): 1077-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11337423&dopt=Abstract
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Women's Initiative for Nonsmoking (WINS V): under-use of nicotine replacement therapy. Author(s): Mahrer-Imhof R, Froelicher ES, Li WW, Parker KM, Benowitz N. Source: Heart & Lung : the Journal of Critical Care. 2002 September-October; 31(5): 36873. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12487015&dopt=Abstract
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Worsening of motor performance in patients with Parkinson's disease following transdermal nicotine administration. Author(s): Ebersbach G, Stock M, Muller J, Wenning G, Wissel J, Poewe W. Source: Movement Disorders : Official Journal of the Movement Disorder Society. 1999 November; 14(6): 1011-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10584678&dopt=Abstract
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Would-be quitters get help winning against nicotine. Author(s): Schultz S. Source: U.S. News & World Report. 2000 May 29; 128(21): 58-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10947311&dopt=Abstract
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A clinico-pathologic presentation. The diagnosis is nicotine stomatitis. Author(s): Cataldo E, Santis HR. Source: J Mass Dent Soc. 1996 Summer; 45(2): 44-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9520686&dopt=Abstract
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A common genetic defect in nicotine metabolism decreases risk for dependence and lowers cigarette consumption. Author(s): Tyndale RF, Pianezza ML, Sellers EM. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 1999; 1 Suppl 2: S63-7; Discussion S69-70. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11768189&dopt=Abstract
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A comparison of a nicotine sublingual tablet and placebo for smoking cessation. Author(s): Glover ED, Glover PN, Franzon M, Sullivan CR, Cerullo CC, Howell RM, Keyes GG, Nilsson F, Hobbs GR. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2002 November; 4(4): 441-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12521403&dopt=Abstract
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A consideration of the role of gas/particle partitioning in the deposition of nicotine and other tobacco smoke compounds in the respiratory tract. Author(s): Pankow JF. Source: Chemical Research in Toxicology. 2001 November; 14(11): 1465-81. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11712903&dopt=Abstract
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A factor analysis of the Fagerstrom Test for Nicotine Dependence (FTND). Author(s): Radzius A, Gallo JJ, Epstein DH, Gorelick DA, Cadet JL, Uhl GE, Moolchan ET. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2003 April; 5(2): 255-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745499&dopt=Abstract
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A functional role for nicotine in Bcl2 phosphorylation and suppression of apoptosis. Author(s): Mai H, May WS, Gao F, Jin Z, Deng X. Source: The Journal of Biological Chemistry. 2003 January 17; 278(3): 1886-91. Epub 2002 November 05. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12421819&dopt=Abstract
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A pilot controlled trial of transdermal nicotine in the treatment of attention deficit hyperactivity disorder. Author(s): Shytle RD, Silver AA, Wilkinson BJ, Sanberg PR. Source: World J Biol Psychiatry. 2002 July; 3(3): 150-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12478880&dopt=Abstract
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A receptor-mediated mechanism of nicotine toxicity in oral keratinocytes. Author(s): Arredondo J, Nguyen VT, Chernyavsky AI, Jolkovsky DL, Pinkerton KE, Grando SA. Source: Laboratory Investigation; a Journal of Technical Methods and Pathology. 2001 December; 81(12): 1653-68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11742036&dopt=Abstract
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A vaccine for nicotine dependence: targeting the drug rather than the brain. Author(s): Pentel P, Malin D. Source: Respiration; International Review of Thoracic Diseases. 2002; 69(3): 193-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12097758&dopt=Abstract
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Abstinence from smoking eight years after participation in randomised controlled trial of nicotine patch. Author(s): Yudkin P, Hey K, Roberts S, Welch S, Murphy M, Walton R. Source: Bmj (Clinical Research Ed.). 2003 July 5; 327(7405): 28-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12842953&dopt=Abstract
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Accelerated metabolism of nicotine and cotinine in pregnant smokers. Author(s): Dempsey D, Jacob P 3rd, Benowitz NL. Source: The Journal of Pharmacology and Experimental Therapeutics. 2002 May; 301(2): 594-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11961061&dopt=Abstract
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Acetylcholine receptor extracellular domain determines sensitivity to nicotineinduced inactivation. Author(s): Kuryatov A, Olale FA, Choi C, Lindstrom J. Source: European Journal of Pharmacology. 2000 March 30; 393(1-3): 11-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10770993&dopt=Abstract
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Activation of phospholipases A2 and D of a human neuroblastoma cell line (LA-N-2) by N-dodecyl-L-lysine amide (compound 24), a putative G protein activator: characteristics of inhibition by (-)-nicotine. Author(s): Garnham BM, Fitzpatrick-Wong S, Schunack W, Nurnberg B, Sorrentino G, Parkinson FE, Kanfer JN, Sitar DS. Source: Neurochemical Research. 2002 December; 27(12): 1613-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12515313&dopt=Abstract
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Acute cardiac effects of nicotine in healthy young adults. Author(s): Jolma CD, Samson RA, Klewer SE, Donnerstein RL, Goldberg SJ. Source: Echocardiography (Mount Kisco, N.Y.). 2002 August; 19(6): 443-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12356338&dopt=Abstract
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Acute effect of nicotine on non-smokers: I. OAEs and ABRs. Author(s): Harkrider AW, Champlin CA, McFadden D. Source: Hearing Research. 2001 October; 160(1-2): 73-88. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11591493&dopt=Abstract
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Acute effect of nicotine on non-smokers: II. MLRs and 40-Hz responses. Author(s): Harkrider AW, Champlin CA. Source: Hearing Research. 2001 October; 160(1-2): 89-98. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11591494&dopt=Abstract
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Acute effect of nicotine on non-smokers: III. LLRs and EEGs. Author(s): Harkrider AW, Champlin CA. Source: Hearing Research. 2001 October; 160(1-2): 99-110. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11591495&dopt=Abstract
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Acute effects of nicotine infusion on platelets in nicotine users with normal and impaired renal function. Author(s): Whiss PA, Lundahl TH, Bengtsson T, Lindahl TL, Lunell E, Larsson R. Source: Toxicology and Applied Pharmacology. 2000 March 1; 163(2): 95-104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10698667&dopt=Abstract
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Acute effects of nicotine withdrawal syndrome in pilots during flight. Author(s): Giannakoulas G, Katramados A, Melas N, Diamantopoulos I, Chimonas E. Source: Aviation, Space, and Environmental Medicine. 2003 March; 74(3): 247-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12650272&dopt=Abstract
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Acute nicotine effects on auditory sensory memory in tacrine-treated and nontreated patients with Alzheimer's disease: an event-related potential study. Author(s): Engeland C, Mahoney C, Mohr E, Ilivitsky V, Knott VJ. Source: Pharmacology, Biochemistry, and Behavior. 2002 May; 72(1-2): 457-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11900820&dopt=Abstract
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Acute nicotine poisoning associated with a traditional remedy for eczema. Author(s): Davies P, Levy S, Pahari A, Martinez D. Source: Archives of Disease in Childhood. 2001 December; 85(6): 500-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11719343&dopt=Abstract
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Acute nicotine reinforcement, but not chronic tolerance, predicts withdrawal and relapse after quitting smoking. Author(s): Perkins KA, Broge M, Gerlach D, Sanders M, Grobe JE, Cherry C, Wilson AS. Source: Health Psychology : Official Journal of the Division of Health Psychology, American Psychological Association. 2002 July; 21(4): 332-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12090675&dopt=Abstract
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Addressing regulatory barriers to licensing nicotine products for smoking reduction. Author(s): West R. Source: Addiction (Abingdon, England). 2000 January; 95 Suppl 1: S29-34. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10723820&dopt=Abstract
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Adolescent nicotine dependence and smoking cessation outcomes. Author(s): Horn K, Fernandes A, Dino G, Massey CJ, Kalsekar I. Source: Addictive Behaviors. 2003 June; 28(4): 769-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12726789&dopt=Abstract
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Adolescent nicotine use. Author(s): McGee R, Williams S, Reeder AI. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2003 March; 42(3): 265. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12595777&dopt=Abstract
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Advances in neuroscience and pharmacology of nicotine. 3rd SRNT Europe Conference, Paris, France, 19-22 September 2001. Author(s): Balfour D, Le Houezec J. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2002 May; 4(2): 229-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12028855&dopt=Abstract
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Advances in non-nicotine pharmacotherapy for smoking cessation. Author(s): Covey LS, Sullivan MA, Johnston JA, Glassman AH, Robinson MD, Adams DP. Source: Drugs. 2000 January; 59(1): 17-31. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10718098&dopt=Abstract
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Air nicotine and saliva cotinine as indicators of workplace passive smoking exposure and risk. Author(s): Repace JL, Jinot J, Bayard S, Emmons K, Hammond SK. Source: Risk Analysis : an Official Publication of the Society for Risk Analysis. 1998 February; 18(1): 71-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9523445&dopt=Abstract
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Airway sensory replacement combined with nicotine replacement for smoking cessation. A randomized, placebo-controlled trial using a citric acid inhaler. Author(s): Westman EC, Behm FM, Rose JE. Source: Chest. 1995 May; 107(5): 1358-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7750331&dopt=Abstract
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Alcohol, tobacco (nicotine) and pancreatic pathophysiology. Author(s): Rayford PL. Source: J Assoc Acad Minor Phys. 2001 March; 12(1-2): 91-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11851197&dopt=Abstract
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Alteration in alpha 2 integrin immunocytochemical expression on cultured human gingival fibroblasts following nicotine exposure. Author(s): Leonardi R, Lanteri E, Stivala F, Caltabiano M, Fenga C, Travali S. Source: Minerva Stomatol. 1999 November; 48(11): 495-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10768008&dopt=Abstract
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An acute dose of nicotine enhances cue-induced cocaine craving. Author(s): Reid MS, Mickalian JD, Delucchi KL, Hall SM, Berger SP. Source: Drug and Alcohol Dependence. 1998 January 1; 49(2): 95-104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9543646&dopt=Abstract
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An anthology of behavioural pharmacology. Commentary on Stolerman's Interspecies consistency in the behavioural pharmacology of nicotine dependence. Author(s): Cohen C. Source: Behavioural Pharmacology. 1999 November; 10(6-7): 585-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10780499&dopt=Abstract
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An investigation of predictors of nicotine abstinence in a smoking cessation treatment study of smokers with a past history of alcohol dependence. Author(s): Kalman D, Tirch D, Penk W, Denison H. Source: Psychology of Addictive Behaviors : Journal of the Society of Psychologists in Addictive Behaviors. 2002 December; 16(4): 346-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12503909&dopt=Abstract
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Anabasine and anatabine as biomarkers for tobacco use during nicotine replacement therapy. Author(s): Jacob P 3rd, Hatsukami D, Severson H, Hall S, Yu L, Benowitz NL. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 2002 December; 11(12): 1668-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12496059&dopt=Abstract
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Another mirror shattered? Tobacco industry involvement suspected in a book which claims that nicotine is not addictive. Author(s): Edwards G, Babor TF, Hall W, West R. Source: Addiction (Abingdon, England). 2002 January; 97(1): 1-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11895259&dopt=Abstract
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Anxiety sensitivity, self-reported motives for alcohol and nicotine use, and level of consumption. Author(s): Novak A, Burgess ES, Clark M, Zvolensky MJ, Brown RA. Source: Journal of Anxiety Disorders. 2003; 17(2): 165-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12614660&dopt=Abstract
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Application of liquid separation techniques to the determination of the main urinary nicotine metabolites. Author(s): Tyrpien K, Wielkoszynski T, Janoszka B, Dobosz C, Bodzek D, Steplewski Z. Source: J Chromatogr A. 2000 February 18; 870(1-2): 29-38. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10722059&dopt=Abstract
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Applying genetic approaches to the treatment of nicotine dependence. Author(s): Lerman C, Niaura R. Source: Oncogene. 2002 October 21; 21(48): 7412-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12379882&dopt=Abstract
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Applying the risk/use equilibrium: use medicinal nicotine now for harm reduction. Author(s): Kozlowski LT, Strasser AA, Giovino GA, Erickson PA, Terza JV. Source: Tobacco Control. 2001 September; 10(3): 201-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11544374&dopt=Abstract
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Are adolescent smokers dependent on nicotine? A review of the evidence. Author(s): Colby SM, Tiffany ST, Shiffman S, Niaura RS. Source: Drug and Alcohol Dependence. 2000 May 1; 59 Suppl 1: S83-95. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10773439&dopt=Abstract
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Are social fears and DSM-IV social anxiety disorder associated with smoking and nicotine dependence in adolescents and young adults? Author(s): Sonntag H, Wittchen HU, Hofler M, Kessler RC, Stein MB. Source: European Psychiatry : the Journal of the Association of European Psychiatrists. 2000 February; 15(1): 67-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10713804&dopt=Abstract
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Assessment of chronic exposure to cigarette smoke and its change during pregnancy by segmental analysis of maternal hair nicotine. Author(s): Pichini S, Garcia-Algar O, Munoz L, Vall O, Pacifici R, Figueroa C, Pascual JA, Diaz D, Sunyer J. Source: Journal of Exposure Analysis and Environmental Epidemiology. 2003 March; 13(2): 144-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12679794&dopt=Abstract
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Assessment of nicotine dependence symptoms in adolescents: a comparison of five indicators. Author(s): O'Loughlin J, DiFranza J, Tarasuk J, Meshefedjian G, McMillan-Davey E, Paradis G, Tyndale RF, Clarke P, Hanley J. Source: Tobacco Control. 2002 December; 11(4): 354-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12432161&dopt=Abstract
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Asthma exacerbation after administration of nicotine nasal spray for smoking cessation. Author(s): Roth MT, Westman EC. Source: Pharmacotherapy. 2002 June; 22(6): 779-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12066970&dopt=Abstract
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Baseline-dependency of nicotine effects: a review. Author(s): Perkins KA. Source: Behavioural Pharmacology. 1999 November; 10(6-7): 597-615. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10780501&dopt=Abstract
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Basic cardiovascular research and its implications for the medicinal use of nicotine. Author(s): Benowitz NL. Source: Journal of the American College of Cardiology. 2003 February 5; 41(3): 497-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12575982&dopt=Abstract
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Be wary of subsidising nicotine replacement therapy. Author(s): Miller C, Kriven S, Rowley D, Abram L. Source: Tobacco Control. 2002 December; 11(4): 380-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12432167&dopt=Abstract
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Behavior therapy and the transdermal nicotine patch: effects on cessation outcome, affect, and coping. Author(s): Cinciripini PM, Cinciripini LG, Wallfisch A, Haque W, Van Vunakis H. Source: Journal of Consulting and Clinical Psychology. 1996 April; 64(2): 314-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8871416&dopt=Abstract
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Behavioral and cognitive effects of smoking: relationship to nicotine addiction. Author(s): Heishman SJ. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 1999; 1 Suppl 2: S143-7; Discussion S165-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11768172&dopt=Abstract
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Behavioral and neural consequences of prenatal exposure to nicotine. Author(s): Ernst M, Moolchan ET, Robinson ML. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2001 June; 40(6): 630-41. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11392340&dopt=Abstract
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Beneficial effects of nicotine and cigarette smoking: the real, the possible and the spurious. Author(s): Baron JA. Source: British Medical Bulletin. 1996 January; 52(1): 58-73. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8746297&dopt=Abstract
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Binding thermodynamics at the human neuronal nicotine receptor. Author(s): Borea PA, Varani K, Gessi S, Gilli P, Gilli G. Source: Biochemical Pharmacology. 1998 April 15; 55(8): 1189-97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9719473&dopt=Abstract
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Blowing smoke: how cigarette manufacturers argued that nicotine is not addictive. Author(s): Sharfstein J. Source: Tobacco Control. 1999 Summer; 8(2): 210-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10478407&dopt=Abstract
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Brain imaging and the effects of caffeine and nicotine. Author(s): Dager SR, Friedman SD. Source: Annals of Medicine. 2000 December; 32(9): 592-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11209966&dopt=Abstract
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Brain reward system activity in major depression and comorbid nicotine dependence. Author(s): Cardenas L, Tremblay LK, Naranjo CA, Herrmann N, Zack M, Busto UE. Source: The Journal of Pharmacology and Experimental Therapeutics. 2002 September; 302(3): 1265-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12183688&dopt=Abstract
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Brainstem 3H-nicotine receptor binding in the sudden infant death syndrome. Author(s): Nachmanoff DB, Panigrahy A, Filiano JJ, Mandell F, Sleeper LA, ValdesDapena M, Krous HF, White WF, Kinney HC. Source: Journal of Neuropathology and Experimental Neurology. 1998 November; 57(11): 1018-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9825938&dopt=Abstract
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Breaking down boundaries in nicotine and tobacco research. Seventh Annual Meeting Society for Research on Nicotine and Tobacco, Seattle, WA, USA. 23-25 March 2001. Author(s): Wetter D. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2001 August; 3(3): 261-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11506770&dopt=Abstract
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Breastfeeding and the use of recreational drugs--alcohol, caffeine, nicotine and marijuana. Author(s): Liston J. Source: Breastfeed Rev. 1998 August; 6(2): 27-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9849117&dopt=Abstract
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Brief residential treatment for nicotine addiction: a five-year follow-up study. Author(s): Hoffman EH, Blackburn C, Cullari S. Source: Psychological Reports. 2001 August; 89(1): 99-105. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11729559&dopt=Abstract
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Brown adipose tissue. III. Effect of ethanol, nicotine and caffeine exposure. Author(s): Sidlo J, Zaviacic M, Trutzova H. Source: Soud Lek. 1996 May; 41(2): 20-2. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9560910&dopt=Abstract
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Bupropion for the treatment of nicotine dependence in spit tobacco users: a pilot study. Author(s): Dale LC, Ebbert JO, Schroeder DR, Croghan IT, Rasmussen DF, Trautman JA, Cox LS, Hurt RD. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2002 August; 4(3): 267-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12215235&dopt=Abstract
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Bupropion: a new treatment for smokers. Nicotine replacement treatment should also be available on the NHS. Author(s): Britton J, Jarvis MJ. Source: Bmj (Clinical Research Ed.). 2000 July 8; 321(7253): 65-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10884238&dopt=Abstract
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Caffeine and nicotine use in an addicted population. Author(s): Hays LR, Farabee D, Miller W. Source: Journal of Addictive Diseases : the Official Journal of the Asam, American Society of Addiction Medicine. 1998; 17(1): 47-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9549602&dopt=Abstract
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Cardiovascular effects of nasal and transdermal nicotine and cigarette smoking. Author(s): Benowitz NL, Hansson A, Jacob P 3rd. Source: Hypertension. 2002 June; 39(6): 1107-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12052850&dopt=Abstract
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Catecholamine and neuropeptide Y secretion from human adrenal chromaffin cells: effect of nicotine and KCl. Author(s): Cavadas C, Ribeiro CA, Cotrim M, Mosimann F, Brunner HR, Grouzmann E. Source: Annals of the New York Academy of Sciences. 2002 October; 971: 332-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12438144&dopt=Abstract
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Cellular and synaptic mechanisms of nicotine addiction. Author(s): Mansvelder HD, McGehee DS. Source: Journal of Neurobiology. 2002 December; 53(4): 606-17. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12436424&dopt=Abstract
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Cellular mechanisms of nicotine addiction. Author(s): Dani JA, De Biasi M. Source: Pharmacology, Biochemistry, and Behavior. 2001 December; 70(4): 439-46. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11796143&dopt=Abstract
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Central role of fibroblast alpha3 nicotinic acetylcholine receptor in mediating cutaneous effects of nicotine. Author(s): Arredondo J, Hall LL, Ndoye A, Nguyen VT, Chernyavsky AI, Bercovich D, Orr-Urtreger A, Beaudet AL, Grando SA. Source: Laboratory Investigation; a Journal of Technical Methods and Pathology. 2003 February; 83(2): 207-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12594236&dopt=Abstract
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Cerebral effects of nicotine during cognition in smokers and non-smokers. Author(s): Ghatan PH, Ingvar M, Eriksson L, Stone-Elander S, Serrander M, Ekberg K, Wahren J. Source: Psychopharmacology. 1998 March; 136(2): 179-89. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9551775&dopt=Abstract
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Changes in conformation and subcellular distribution of alpha4beta2 nicotinic acetylcholine receptors revealed by chronic nicotine treatment and expression of subunit chimeras. Author(s): Harkness PC, Millar NS. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2002 December 1; 22(23): 10172-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12451118&dopt=Abstract
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Changing places: illicit drugs, medicines, tobacco and nicotine in the nineteenth and twentieth centuries. Author(s): Berridge V. Source: Clio Medica (Amsterdam, Netherlands). 2002; 66: 11-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12028669&dopt=Abstract
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Characterization of nicotine and cotinine N-glucuronidations in human liver microsomes. Author(s): Nakajima M, Tanaka E, Kwon JT, Yokoi T. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2002 December; 30(12): 1484-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12433823&dopt=Abstract
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Chlorination of guanosine and other nucleosides by hypochlorous acid and myeloperoxidase of activated human neutrophils. Catalysis by nicotine and trimethylamine. Author(s): Masuda M, Suzuki T, Friesen MD, Ravanat JL, Cadet J, Pignatelli B, Nishino H, Ohshima H. Source: The Journal of Biological Chemistry. 2001 November 2; 276(44): 40486-96. Epub 2001 August 31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11533049&dopt=Abstract
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Chronic nicotine treatment reduces beta-amyloidosis in the brain of a mouse model of Alzheimer's disease (APPsw). Author(s): Nordberg A, Hellstrom-Lindahl E, Lee M, Johnson M, Mousavi M, Hall R, Perry E, Bednar I, Court J. Source: Journal of Neurochemistry. 2002 May; 81(3): 655-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12065674&dopt=Abstract
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Chronic tolerance to nicotine in humans and its relationship to tobacco dependence. Author(s): Perkins KA. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2002 November; 4(4): 405-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12521400&dopt=Abstract
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Chronic treatment with nicotine or potassium attenuates depolarisation-evoked noradrenaline release from the human neuroblastoma SH-SY5Y. Author(s): Agis-Torres A, Ball SG, Vaughan PF. Source: Neuroscience Letters. 2002 October 18; 331(3): 167-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12383923&dopt=Abstract
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Cigarette nicotine yields and nicotine intake among Japanese male workers. Author(s): Ueda K, Kawachi I, Nakamura M, Nogami H, Shirokawa N, Masui S, Okayama A, Oshima A. Source: Tobacco Control. 2002 March; 11(1): 55-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11891369&dopt=Abstract
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Cigarette-derived nicotine is not a medicine. Author(s): Parrott AC. Source: World J Biol Psychiatry. 2003 April; 4(2): 49-55. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12692774&dopt=Abstract
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Clinical effects of locally delivered nicotine in obstructive sleep apnea syndrome. Author(s): Zevin S, Swed E, Cahan C. Source: American Journal of Therapeutics. 2003 May-June; 10(3): 170-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12756424&dopt=Abstract
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Clinical trial comparing nicotine replacement therapy (NRT) plus brief counselling, brief counselling alone, and minimal intervention on smoking cessation in hospital inpatients. Author(s): Molyneux A, Lewis S, Leivers U, Anderton A, Antoniak M, Brackenridge A, Nilsson F, McNeill A, West R, Moxham J, Britton J. Source: Thorax. 2003 June; 58(6): 484-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12775857&dopt=Abstract
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Cocaine-like subjective effects of nicotine are not blocked by the D1 selective antagonist ecopipam (SCH 39166). Author(s): Chausmer AL, Smith BJ, Kelly RY, Griffiths RR. Source: Behavioural Pharmacology. 2003 March; 14(2): 111-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12658071&dopt=Abstract
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Cognitive effects of nicotine in humans: an fMRI study. Author(s): Kumari V, Gray JA, ffytche DH, Mitterschiffthaler MT, Das M, Zachariah E, Vythelingum GN, Williams SC, Simmons A, Sharma T. Source: Neuroimage. 2003 July; 19(3): 1002-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12880828&dopt=Abstract
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Cognitive mechanisms of nicotine on visual attention. Author(s): Lawrence NS, Ross TJ, Stein EA. Source: Neuron. 2002 October 24; 36(3): 539-48. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12408855&dopt=Abstract
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Combination nicotine replacement therapy for smoking cessation: rationale, efficacy and tolerability. Author(s): Sweeney CT, Fant RV, Fagerstrom KO, McGovern JF, Henningfield JE. Source: Cns Drugs. 2001; 15(6): 453-67. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11524024&dopt=Abstract
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Commentary on: "Effects of scopolamine and nicotine on human rapid information processing performance." Psychopharmacology (1984) 82:147-150. Nicotine improves information processing: saying the unthinkable. Author(s): Warburton DM. Source: Psychopharmacology. 2002 August; 162(4): 345-8. Epub 2002 June 27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12172687&dopt=Abstract
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Comparative effects of tobacco smoking and nasal nicotine. Author(s): Teter CJ, Asfaw B, Ni L, Lutz M, Domino EF, Guthrie SK. Source: European Journal of Clinical Pharmacology. 2002 August; 58(5): 309-14. Epub 2002 June 27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12185553&dopt=Abstract
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Comparison of nicotine patch alone versus nicotine nasal spray alone versus a combination for treating smokers: a minimal intervention, randomized multicenter trial in a nonspecialized setting. Author(s): Croghan GA, Sloan JA, Croghan IT, Novotny P, Hurt RD, DeKrey WL, Mailliard JA, Ebbert LP, Swan DK, Walsh DJ, Wiesenfeld M, Levitt R, Stella P, Johnson PA, Tschetter LK, Loprinzi C. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2003 April; 5(2): 181-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745490&dopt=Abstract
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Comparison of plasma levels of cytokines and in vitro generation of reactive oxygen species after nicotine infusion in nicotine users with normal and impaired renal function. Author(s): Whiss PA, Bengtsson T, Larsson R. Source: Immunopharmacology and Immunotoxicology. 2003 May; 25(2): 131-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12784908&dopt=Abstract
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Comparison of the effects of combined nicotine replacement therapy vs. cigarette smoking in males. Author(s): Haustein KO, Krause J, Haustein H, Rasmussen T, Cort N. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2003 April; 5(2): 195-203. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745492&dopt=Abstract
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Comparison of the pharmacokinetics of two nicotine transdermal systems: nicoderm and habitrol. Author(s): Gupta SK, Okerholm RA, Eller M, Wei G, Rolf CN, Gorsline J. Source: Journal of Clinical Pharmacology. 1995 May; 35(5): 493-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7657849&dopt=Abstract
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Conflict of interest and the credibility of nicotine and tobacco research. Author(s): Swan GE, Balfour DJ. Source: Addiction (Abingdon, England). 2002 January; 97(1): 100-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11898765&dopt=Abstract
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Conflicting evidence for the dopamine release theory of nicotine/tobacco dependence. Author(s): Domino EF. Source: Nihon Shinkei Seishin Yakurigaku Zasshi. 2002 October; 22(5): 181-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12451690&dopt=Abstract
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Contingent monetary reinforcement of smoking reductions, with and without transdermal nicotine, in outpatients with schizophrenia. Author(s): Tidey JW, O'Neill SC, Higgins ST. Source: Experimental and Clinical Psychopharmacology. 2002 August; 10(3): 241-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12233984&dopt=Abstract
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Contribution of nicotine to acute endothelial dysfunction in long-term smokers. Author(s): Neunteufl T, Heher S, Kostner K, Mitulovic G, Lehr S, Khoschsorur G, Schmid RW, Maurer G, Stefenelli T. Source: Journal of the American College of Cardiology. 2002 January 16; 39(2): 251-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11788216&dopt=Abstract
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Controlled trial of three weeks nicotine replacement treatment in hospital patients also given advice and support. Author(s): Hand S, Edwards S, Campbell IA, Cannings R. Source: Thorax. 2002 August; 57(8): 715-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12149533&dopt=Abstract
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Correlates of expired air carbon monoxide: effect of ethnicity and relationship with saliva cotinine and nicotine. Author(s): Berlin I, Radzius A, Henningfield JE, Moolchan ET. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2001 November; 3(4): 325-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11694199&dopt=Abstract
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Correlation and predictive performances of saliva and plasma nicotine concentration on tobacco withdrawal-induced craving. Author(s): Teneggi V, Squassante L, Iavarone L, Milleri S, Bye A, Gomeni R. Source: British Journal of Clinical Pharmacology. 2002 October; 54(4): 407-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12392589&dopt=Abstract
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Could nicotine be beneficial for Behcet's disease? Author(s): Kaklamani VG, Markomichelakis N, Kaklamanis PG. Source: Clinical Rheumatology. 2002 August; 21(4): 341-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12296287&dopt=Abstract
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Cue dependency of nicotine self-administration and smoking. Author(s): Caggiula AR, Donny EC, White AR, Chaudhri N, Booth S, Gharib MA, Hoffman A, Perkins KA, Sved AF. Source: Pharmacology, Biochemistry, and Behavior. 2001 December; 70(4): 515-30. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11796151&dopt=Abstract
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Current evidence for neuroprotective effects of nicotine and caffeine against Parkinson's disease. Author(s): Ross GW, Petrovitch H. Source: Drugs & Aging. 2001; 18(11): 797-806. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11772120&dopt=Abstract
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Current models of nicotine dependence: what is known and what is needed to advance understanding of tobacco etiology among youth. Author(s): Shadel WG, Shiffman S, Niaura R, Nichter M, Abrams DB. Source: Drug and Alcohol Dependence. 2000 May 1; 59 Suppl 1: S9-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10773435&dopt=Abstract
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Cytisine derivatives as ligands for neuronal nicotine receptors and with various pharmacological activities. Author(s): Boido CC, Tasso B, Boido V, Sparatore F. Source: Farmaco (Societa Chimica Italiana : 1989). 2003 March; 58(3): 265-77. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12620422&dopt=Abstract
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Deficient cotinine formation from nicotine is attributed to the whole deletion of the CYP2A6 gene in humans. Author(s): Nakajima M, Yamagishi S, Yamamoto H, Yamamoto T, Kuroiwa Y, Yokoi T. Source: Clinical Pharmacology and Therapeutics. 2000 January; 67(1): 57-69. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10668854&dopt=Abstract
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Deficient C-oxidation of nicotine continued. Author(s): Benowitz NL, Griffin C, Tyndale R. Source: Clinical Pharmacology and Therapeutics. 2001 December; 70(6): 567. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11753274&dopt=Abstract
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Deficient C-oxidation of nicotine. Author(s): Benowitz NL, Jacob P 3rd, Sachs DP. Source: Clinical Pharmacology and Therapeutics. 1995 May; 57(5): 590-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7768082&dopt=Abstract
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Delirium from nicotine withdrawal in neuro-ICU patients. Author(s): Mayer SA, Chong JY, Ridgway E, Min KC, Commichau C, Bernardini GL. Source: Neurology. 2001 August 14; 57(3): 551-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11502936&dopt=Abstract
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Delivery devices and protecting the next generation from nicotine. Author(s): Barrett J. Source: Molecular Medicine Today. 1995 November; 1(8): 351. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9415179&dopt=Abstract
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Depression and nicotine: preclinical and clinical evidence for common mechanisms. Author(s): Laje RP, Berman JA, Glassman AH. Source: Current Psychiatry Reports. 2001 December; 3(6): 470-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11707160&dopt=Abstract
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Depression and self-medication with nicotine: the modifying influence of the dopamine D4 receptor gene. Author(s): Lerman C, Caporaso N, Main D, Audrain J, Boyd NR, Bowman ED, Shields PG. Source: Health Psychology : Official Journal of the Division of Health Psychology, American Psychological Association. 1998 January; 17(1): 56-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9459071&dopt=Abstract
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Depressive symptoms and smoking cessation among inner-city African Americans using the nicotine patch. Author(s): Catley D, Ahluwalia JS, Resnicow K, Nazir N. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2003 February; 5(1): 61-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745507&dopt=Abstract
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Deprivation state but not nicotine content of the cigarette affects responding by smokers on a progressive ratio task. Author(s): Rusted JM, Mackee A, Williams R, Willner P. Source: Psychopharmacology. 1998 December; 140(4): 411-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9888615&dopt=Abstract
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Determination of nicotine as an indicator of environmental tobacco smoke in restaurants. Author(s): Kuusimaki L, Pfaffli P, Froshaug M, Becher G, Dybing E, Peltonen K. Source: American Journal of Industrial Medicine. 1999 September; Suppl 1: 152-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10519819&dopt=Abstract
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Determination of nicotine in water by gradient ion chromatography. Author(s): Ayers GP, Selleck PW, Gillett RW, Keywood MD. Source: J Chromatogr A. 1998 October 23; 824(2): 241-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9818435&dopt=Abstract
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Determination of nicotine N-1-glucuronide, a quaternary N-glucuronide conjugate, in human biological samples. Author(s): Byrd GD, Caldwell WS, Bhatti BS, Ravard A, Crooks PA. Source: Drug Metabol Drug Interact. 2000; 16(4): 281-97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11201307&dopt=Abstract
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Determination of the nicotine content of various edible nightshades (Solanaceae) and their products and estimation of the associated dietary nicotine intake. Author(s): Siegmund B, Leitner E, Pfannhauser W. Source: Journal of Agricultural and Food Chemistry. 1999 August; 47(8): 3113-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10552617&dopt=Abstract
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Development and evaluation of a biphasic buccal adhesive tablet for nicotine replacement therapy. Author(s): Park CR, Munday DL. Source: International Journal of Pharmaceutics. 2002 April 26; 237(1-2): 215-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11955819&dopt=Abstract
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Development of a rectal nicotine delivery system for the treatment of ulcerative colitis. Author(s): Dash AK, Gong Z, Miller DW, Huai-Yan H, Laforet J. Source: International Journal of Pharmaceutics. 1999 November 10; 190(1): 21-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10528093&dopt=Abstract
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Development of a screening questionnaire for tobacco/nicotine dependence according to ICD-10, DSM-III-R, and DSM-IV. Author(s): Kawakami N, Takatsuka N, Inaba S, Shimizu H. Source: Addictive Behaviors. 1999 March-April; 24(2): 155-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10336098&dopt=Abstract
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Development of a versatile method for the detection of nicotine in air. Author(s): Pendergrass SM, Krake AM, Jaycox LB. Source: Aihaj : a Journal for the Science of Occupational and Environmental Health and Safety. 2000 July-August; 61(4): 469-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10976675&dopt=Abstract
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Developmental cholinotoxicants: nicotine and chlorpyrifos. Author(s): Slotkin TA. Source: Environmental Health Perspectives. 1999 February; 107 Suppl 1: 71-80. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10229709&dopt=Abstract
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Diagnosis and treatment of nicotine dependence with emphasis on nicotine replacement therapy. A status report. Author(s): Balfour D, Benowitz N, Fagerstrom K, Kunze M, Keil U. Source: European Heart Journal. 2000 March; 21(6): 438-45. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10681484&dopt=Abstract
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Direct and indirect effects of nicotine/smoking on cognition in humans. Author(s): Waters AJ, Sutton SR. Source: Addictive Behaviors. 2000 January-February; 25(1): 29-43. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10708317&dopt=Abstract
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Direct block of inward rectifier potassium channels by nicotine. Author(s): Wang H, Yang B, Zhang L, Xu D, Wang Z. Source: Toxicology and Applied Pharmacology. 2000 April 1; 164(1): 97-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10739749&dopt=Abstract
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Discriminative stimulus properties of nicotine at low doses: the effects of caffeine preload. Author(s): Duka T, Tasker R, Russell K, Stephens DN. Source: Behavioural Pharmacology. 1998 May; 9(3): 219-29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9832936&dopt=Abstract
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Dissociating nicotine and nonnicotine components of cigarette smoking. Author(s): Rose JE, Behm FM, Westman EC, Johnson M. Source: Pharmacology, Biochemistry, and Behavior. 2000 September; 67(1): 71-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11113486&dopt=Abstract
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Dissociation of nicotine tolerance from tobacco dependence in humans. Author(s): Perkins KA, Gerlach D, Broge M, Grobe JE, Sanders M, Fonte C, Vender J, Cherry C, Wilson A. Source: The Journal of Pharmacology and Experimental Therapeutics. 2001 March; 296(3): 849-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11181916&dopt=Abstract
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Distal ulcerative colitis refractory to rectal mesalamine: role of transdermal nicotine versus oral mesalamine. Author(s): Guslandi M, Frego R, Viale E, Testoni PA. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2002 May; 16(5): 293-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12045777&dopt=Abstract
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Distinguishing nicotine dependence from smoking: why it matters to tobacco control and psychiatry. Author(s): Hughes JR. Source: Archives of General Psychiatry. 2001 September; 58(9): 817-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11545663&dopt=Abstract
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Diversity of selective environmental substrates for human cytochrome P450 2A6: alkoxyethers, nicotine, coumarin, N-nitrosodiethylamine, and Nnitrosobenzylmethylamine. Author(s): Le Gal A, Dreano Y, Lucas D, Berthou F. Source: Toxicology Letters. 2003 September 15; 144(1): 77-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12919726&dopt=Abstract
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Do adolescent smokers experience withdrawal effects when deprived of nicotine? Author(s): Killen JD, Ammerman S, Rojas N, Varady J, Haydel F, Robinson TN. Source: Experimental and Clinical Psychopharmacology. 2001 May; 9(2): 176-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11518093&dopt=Abstract
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Do heavy smokers benefit from higher dose nicotine patch therapy? Author(s): Killen JD, Fortmann SP, Davis L, Strausberg L, Varady A. Source: Experimental and Clinical Psychopharmacology. 1999 August; 7(3): 226-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10472510&dopt=Abstract
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Doctors told to treat nicotine addiction as a disease. Author(s): Kmietowicz Z. Source: Bmj (Clinical Research Ed.). 2000 February 12; 320(7232): 397. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10669428&dopt=Abstract
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Does a reduced sensitivity to bitter taste increase the risk of becoming nicotine addicted? Author(s): Enoch MA, Harris CR, Goldman D. Source: Addictive Behaviors. 2001 May-June; 26(3): 399-404. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11436931&dopt=Abstract
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Does abstinence from smoking or a transdermal nicotine system influence atracurium-induced neuromuscular block? Author(s): Puura AI, Rorarius MG, Laippala P, Baer GA. Source: Anesthesia and Analgesia. 1998 August; 87(2): 430-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9706945&dopt=Abstract
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Does over-the-counter nicotine replacement therapy improve smokers' life expectancy? Author(s): Lawrence WF, Smith SS, Baker TB, Fiore MC. Source: Tobacco Control. 1998 Winter; 7(4): 364-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10093169&dopt=Abstract
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Does smoking reduction result in reduction of biomarkers associated with harm? A pilot study using a nicotine inhaler. Author(s): Hurt RD, Croghan GA, Wolter TD, Croghan IT, Offord KP, Williams GM, Djordjevic MV, Richie JP Jr, Jeffrey AM. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2000 November; 2(4): 327-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11197312&dopt=Abstract
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Dopamine agonist and antagonist responders as related to types of nicotine craving and facets of extraversion. Author(s): Reuter M, Netter P, Toll C, Hennig J. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2002 June; 26(5): 845-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12369256&dopt=Abstract
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Dose effects of nicotine gum. Author(s): Gross J, Johnson J, Sigler L, Stitzer ML. Source: Addictive Behaviors. 1995 May-June; 20(3): 371-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7653318&dopt=Abstract
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Dose-dependent stereoselective activation of the trigeminal sensory system by nicotine in man. Author(s): Thuerauf N, Kaegler M, Dietz R, Barocka A, Kobal G. Source: Psychopharmacology. 1999 March; 142(3): 236-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10208315&dopt=Abstract
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Doses of nicotine and lung carcinogens delivered to cigarette smokers. Author(s): Djordjevic MV, Stellman SD, Zang E. Source: Journal of the National Cancer Institute. 2000 January 19; 92(2): 106-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10639511&dopt=Abstract
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Double-blind placebo controlled trial of dextrose tablets and nicotine patch in smoking cessation. Author(s): West R, Willis N. Source: Psychopharmacology. 1998 March; 136(2): 201-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9551778&dopt=Abstract
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Drug may suppress the craving for nicotine. Author(s): Wickelgren I. Source: Science. 1998 December 4; 282(5395): 1797,1799. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9874627&dopt=Abstract
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Early emotional disturbances during nicotine patch therapy in subjects with and without a history of depression. Author(s): Carton S, Le Houezec J, Lagrue G, Jouvent R. Source: Journal of Affective Disorders. 2002 November; 72(2): 195-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12200210&dopt=Abstract
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Effect of chewing gum containing nicotine and caffeine on energy expenditure and substrate utilization in men. Author(s): Jessen AB, Toubro S, Astrup A. Source: The American Journal of Clinical Nutrition. 2003 June; 77(6): 1442-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12791621&dopt=Abstract
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Effect of nicotine and nicotinic receptors on anxiety and depression. Author(s): Picciotto MR, Brunzell DH, Caldarone BJ. Source: Neuroreport. 2002 July 2; 13(9): 1097-106. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12151749&dopt=Abstract
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Effect of nicotine replacement and quitting smoking on circulating adhesion molecule profiles (sICAM-1, sCD44v5, sCD44v6). Author(s): Palmer RM, Stapleton JA, Sutherland G, Coward PY, Wilson RF, Scott DA. Source: European Journal of Clinical Investigation. 2002 November; 32(11): 852-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12423327&dopt=Abstract
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Effect of smoking and transdermal nicotine on colonic nicotinic acetylcholine receptors in ulcerative colitis. Author(s): Richardson CE, Morgan JM, Jasani B, Green JT, Rhodes J, Williams GT, Lindstrom J, Wonnacott S, Peel S, Thomas GA. Source: Qjm : Monthly Journal of the Association of Physicians. 2003 January; 96(1): 5765. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12509650&dopt=Abstract
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Effect on smoking cessation of switching nicotine replacement therapy to over-thecounter status. Author(s): Thorndike AN, Biener L, Rigotti NA. Source: American Journal of Public Health. 2002 March; 92(3): 437-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11867326&dopt=Abstract
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Effectiveness of over-the-counter nicotine replacement therapy. Author(s): Franzon M, Gustavsson G, Korberly BH. Source: Jama : the Journal of the American Medical Association. 2002 December 25; 288(24): 3108; Author Reply 3110. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12495386&dopt=Abstract
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Effectiveness of over-the-counter nicotine replacement therapy. Author(s): Antonuccio DO. Source: Jama : the Journal of the American Medical Association. 2002 December 25; 288(24): 3108; Author Reply 3110. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12495385&dopt=Abstract
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Effectiveness of over-the-counter nicotine replacement therapy. Author(s): Stead LF, Davis RM, Fiore MC, Hatsukami DK, Raw M, West R. Source: Jama : the Journal of the American Medical Association. 2002 December 25; 288(24): 3109-10; Author Reply 3110. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12495384&dopt=Abstract
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Effectiveness of over-the-counter nicotine replacement therapy. Author(s): Cadore JM. Source: Jama : the Journal of the American Medical Association. 2002 December 25; 288(24): 3108-9; Author Reply 3110. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12495383&dopt=Abstract
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Effects of a low dose of transdermal nicotine on information processing. Author(s): Davranche K, Audiffren M. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2002 August; 4(3): 275-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12215236&dopt=Abstract
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Effects of acute nicotine administration on cognitive event-related potentials in tacrine-treated and non-treated patients with Alzheimer's disease. Author(s): Knott V, Mohr E, Mahoney C, Engeland C, Ilivitsky V. Source: Neuropsychobiology. 2002; 45(3): 156-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11979067&dopt=Abstract
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Effects of alkaline phosphatase and its inhibitor levamisole on the modulation of androgen metabolism by nicotine and minocycline in human gingival and oral periosteal fibroblasts. Author(s): Soory M, Suchak A. Source: Archives of Oral Biology. 2003 January; 48(1): 69-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12615144&dopt=Abstract
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Effects of cigarette nicotine content and smoking pace on subsequent craving and smoking. Author(s): Dallery J, Houtsmuller EJ, Pickworth WB, Stitzer ML. Source: Psychopharmacology. 2003 January; 165(2): 172-80. Epub 2002 October 31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12417964&dopt=Abstract
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Effects of cigarette smoking and nicotine nasal spray on psychiatric symptoms and cognition in schizophrenia. Author(s): Smith RC, Singh A, Infante M, Khandat A, Kloos A. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2002 September; 27(3): 479-97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12225705&dopt=Abstract
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Effects of cigarette smoking or nicotine replacement on cardiovascular risk factors and parameters of haemorheology. Author(s): Haustein KO, Krause J, Haustein H, Rasmussen T, Cort N. Source: Journal of Internal Medicine. 2002 August; 252(2): 130-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12190888&dopt=Abstract
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Effects of nicotine chewing gum on UPDRS score and P300 in early-onset parkinsonism. Author(s): Mitsuoka T, Kaseda Y, Yamashita H, Kohriyama T, Kawakami H, Nakamura S, Yamamura Y. Source: Hiroshima J Med Sci. 2002 March; 51(1): 33-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11999458&dopt=Abstract
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Effects of nicotine deprivation on alcohol-related information processing and drinking behavior. Author(s): Palfai TP, Monti PM, Ostafin B, Hutchison K. Source: Journal of Abnormal Psychology. 2000 February; 109(1): 96-105. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10740940&dopt=Abstract
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Effects of nicotine deprivation on craving response covariation in smokers. Author(s): Sayette MA, Martin CS, Hull JG, Wertz JM, Perrott MA. Source: Journal of Abnormal Psychology. 2003 February; 112(1): 110-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12653419&dopt=Abstract
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Effects of nicotine deprivation on urges to drink and smoke in alcoholic smokers. Author(s): Cooney JL, Cooney NL, Pilkey DT, Kranzler HR, Oncken CA. Source: Addiction (Abingdon, England). 2003 July; 98(7): 913-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12814497&dopt=Abstract
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Effects of nicotine dose, instructional set, and outcome expectancies on the subjective effects of smoking in the presence of a stressor. Author(s): Juliano LM, Brandon TH. Source: Journal of Abnormal Psychology. 2002 February; 111(1): 88-97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11866182&dopt=Abstract
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Effects of nicotine on alcohol consumption. Author(s): Le AD. Source: Alcoholism, Clinical and Experimental Research. 2002 December; 26(12): 1915-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12500118&dopt=Abstract
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Effects of nicotine on intercellular adhesion molecule expression in endothelial cells and integrin expression in neutrophils in vitro. Author(s): Speer P, Zhang Y, Gu Y, Lucas MJ, Wang Y. Source: American Journal of Obstetrics and Gynecology. 2002 March; 186(3): 551-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11904622&dopt=Abstract
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Effects of nicotine, dimethylphenylpiperazinium and tetramethylammonium on smooth muscles from feline and human gastric corpus. Author(s): Jankovic SM, Beleslin DB. Source: Pharmacological Research : the Official Journal of the Italian Pharmacological Society. 2000 May; 41(5): 577-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10753558&dopt=Abstract
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Effects of sex hormones, forskolin, and nicotine on choline acetyltransferase activity in human isolated placenta. Author(s): Wessler I, Schwarze S, Brockerhoff P, Bittinger F, Kirkpatrick CJ, Kilbinger H. Source: Neurochemical Research. 2003 April; 28(3-4): 489-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12675136&dopt=Abstract
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Effects of the nicotine patch on performance during the first week of smoking cessation. Author(s): Cook MR, Gerkovich MM, Graham C, Hoffman SJ, Peterson RC. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2003 April; 5(2): 169-80. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745489&dopt=Abstract
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Effects of transdermal nicotine on learning, memory, verbal fluency, concentration, and general health in a healthy sample at risk for dementia. Author(s): Howe MN, Price IR. Source: Int Psychogeriatr. 2001 December; 13(4): 465-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12003253&dopt=Abstract
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Effects of transdermal nicotine patches on abstinence-induced and cue-elicited craving in cigarette smokers. Author(s): Tiffany ST, Cox LS, Elash CA. Source: Journal of Consulting and Clinical Psychology. 2000 April; 68(2): 233-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10780123&dopt=Abstract
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Effects of whole deletion of CYP2A6 on nicotine metabolism in humans. Author(s): Zhang X, Ameno K, Ameno S, Kinoshita H, Kubota T, Kumihashi M, Mostofa J, Iwahashi K, Ijiri I. Source: Drug and Chemical Toxicology. 2002 May; 25(2): 203-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12024803&dopt=Abstract
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Efficacy of a nicotine lozenge for smoking cessation. Author(s): Shiffman S, Dresler CM, Hajek P, Gilburt SJ, Targett DA, Strahs KR. Source: Archives of Internal Medicine. 2002 June 10; 162(11): 1267-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12038945&dopt=Abstract
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Efficacy of acute administration of nicotine gum in relief of cue-provoked cigarette craving. Author(s): Shiffman S, Shadel WG, Niaura R, Khayrallah MA, Jorenby DE, Ryan CF, Ferguson CL. Source: Psychopharmacology. 2003 April; 166(4): 343-50. Epub 2003 February 25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12601502&dopt=Abstract
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Efficacy of nicotine patch in smokers with a history of alcoholism. Author(s): Hughes JR, Novy P, Hatsukami DK, Jensen J, Callas PW. Source: Alcoholism, Clinical and Experimental Research. 2003 June; 27(6): 946-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12824815&dopt=Abstract
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Efficacy of oral transmucosal nicotine lozenge for suppression of withdrawal symptoms in smoking abstinence. Author(s): Muramoto ML, Ranger-Moore J, Leischow SJ. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2003 April; 5(2): 223-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745495&dopt=Abstract
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Efficacy of over-the-counter nicotine patch. Author(s): Shiffman S, Gorsline J, Gorodetzky CW. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2002 November; 4(4): 477-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12521407&dopt=Abstract
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Elucidating the role of genetic factors in smoking behavior and nicotine dependence. Author(s): Lerman C, Berrettini W. Source: American Journal of Medical Genetics. 2003 April 1; 118B(1): 48-54. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12627466&dopt=Abstract
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Enhanced Escherichia coli invasion of human brain microvascular endothelial cells is associated with alternations in cytoskeleton induced by nicotine. Author(s): Chen YH, Chen SH, Jong A, Zhou ZY, Li W, Suzuki K, Huang SH. Source: Cellular Microbiology. 2002 August; 4(8): 503-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12174085&dopt=Abstract
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Ethanol and nicotine: a pharmacologic balancing act? Author(s): Prendergast MA, Rogers DT, Barron S, Bardo MT, Littleton JM. Source: Alcoholism, Clinical and Experimental Research. 2002 December; 26(12): 1917-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12500119&dopt=Abstract
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Evaluation of subclinical respiratory tract inflammation in heavy smokers who switch to a cigarette-like nicotine delivery device that primarily heats tobacco. Author(s): Rennard SI, Umino T, Millatmal T, Daughton DM, Manouilova LS, Ullrich FA, Patil KD, Romberger DJ, Floreani AA, Anderson JR. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2002 November; 4(4): 467-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12521406&dopt=Abstract
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Evidence for the immunosuppressive role of nicotine on human dendritic cell functions. Author(s): Nouri-Shirazi M, Guinet E. Source: Immunology. 2003 July; 109(3): 365-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12807482&dopt=Abstract
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Evidence that transient nicotine lowers the body weight set point. Author(s): Cabanac M, Frankham P. Source: Physiology & Behavior. 2002 August; 76(4-5): 539-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12126990&dopt=Abstract
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Failure to reduce nicotine addiction in young adults with diabetes. Author(s): Ismail AA, Wallymahmed ME, Gill GV, MacFarlane IA. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 2000 April; 17(4): 330-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10821303&dopt=Abstract
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FDA and EPA setbacks, fetal nicotine, ASH Thailand and UK, tennis shame, Australian documents, Corporate Activity Project, and 2100 quotes. Author(s): Cannon J. Source: Tobacco Control. 1998 Autumn; 7(3): 320-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9825427&dopt=Abstract
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Fetal growth and length of gestation in relation to prenatal exposure to environmental tobacco smoke assessed by hair nicotine concentration. Author(s): Jaakkola JJ, Jaakkola N, Zahlsen K. Source: Environmental Health Perspectives. 2001 June; 109(6): 557-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11445507&dopt=Abstract
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Fetal nicotine or cocaine exposure: which one is worse? Author(s): Slotkin TA. Source: The Journal of Pharmacology and Experimental Therapeutics. 1998 June; 285(3): 931-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9618392&dopt=Abstract
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Filter ventilation and nicotine content of tobacco in cigarettes from Canada, the United Kingdom, and the United States. Author(s): Kozlowski LT, Mehta NY, Sweeney CT, Schwartz SS, Vogler GP, Jarvis MJ, West RJ. Source: Tobacco Control. 1998 Winter; 7(4): 369-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10093170&dopt=Abstract
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First and second transmembrane segments of alpha3, alpha4, beta2, and beta4 nicotinic acetylcholine receptor subunits influence the efficacy and potency of nicotine. Author(s): Rush R, Kuryatov A, Nelson ME, Lindstrom J. Source: Molecular Pharmacology. 2002 June; 61(6): 1416-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12021403&dopt=Abstract
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First experiences of prescribing nicotine replacement therapy as part of a smoking cessation service on an SSBN patrol. Author(s): Martin N. Source: J R Nav Med Serv. 2002; 88(2): 57-60. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12500484&dopt=Abstract
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Flavor improvement does not increase abuse liability of nicotine chewing gum. Author(s): Houtsmuller EJ, Fant RV, Eissenberg TE, Henningfield JE, Stitzer ML. Source: Pharmacology, Biochemistry, and Behavior. 2002 June; 72(3): 559-68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12175452&dopt=Abstract
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Flow injection Fourier transform infrared determination of nicotine in tobacco. Author(s): Garrigues JM, Perez-Ponce A, Garrigues S, de la Guardia M. Source: The Analyst. 1999 May; 124(5): 783-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10616740&dopt=Abstract
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Focus groups with pregnant smokers: barriers to cessation, attitudes to nicotine patch use and perceptions of cessation counselling by care providers. Author(s): Hotham ED, Atkinson ER, Gilbert AL. Source: Drug and Alcohol Review. 2002 June; 21(2): 163-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12188995&dopt=Abstract
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Formation and retention of cotinine during placental transfer of nicotine in human placental cotyledon. Author(s): Sastry BV, Chance MB, Hemontolor ME, Goddijn-Wessel TA. Source: Pharmacology. 1998 August; 57(2): 104-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9691230&dopt=Abstract
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Formation of the quaternary ammonium-linked glucuronide of nicotine in human liver microsomes: identification and stereoselectivity in the kinetics. Author(s): Ghosheh O, Vashishtha SC, Hawes EM. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2001 December; 29(12): 1525-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11717169&dopt=Abstract
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Forum. Which aspects of nicotine addiction should concern mental health professionials? Author(s): Glassman AH, Hercher LS. Source: The Harvard Mental Health Letter / from Harvard Medical School. 1999 August; 16(2): 8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10402317&dopt=Abstract
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Four-week nicotine skin patch treatment effects on cognitive performance in Alzheimer's disease. Author(s): White HK, Levin ED. Source: Psychopharmacology. 1999 April; 143(2): 158-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10326778&dopt=Abstract
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Framing the nicotine debate: a cultural approach to risk. Author(s): Murphy P. Source: Health Communication. 2001; 13(2): 119-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11451101&dopt=Abstract
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Free nicotine patches plus proactive telephone peer support to help low-income women stop smoking. Author(s): Solomon LJ, Scharoun GM, Flynn BS, Secker-Walker RH, Sepinwall D. Source: Preventive Medicine. 2000 July; 31(1): 68-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10896845&dopt=Abstract
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Functional and developmental studies of the peripheral arterial chemoreceptors in rat: effects of nicotine and possible relation to sudden infant death syndrome. Author(s): Holgert H, Hokfelt T, Hertzberg T, Lagercrantz H. Source: Proceedings of the National Academy of Sciences of the United States of America. 1995 August 1; 92(16): 7575-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7638233&dopt=Abstract
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Functional deactivation of the major neuronal nicotinic receptor caused by nicotine and a protein kinase C-dependent mechanism. Author(s): Eilers H, Schaeffer E, Bickler PE, Forsayeth JR. Source: Molecular Pharmacology. 1997 December; 52(6): 1105-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9415721&dopt=Abstract
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Gabapentin for misuse of homemade nicotine nasal spray. Author(s): Myrick H, Malcolm R, Henderson S, McCormick K. Source: The American Journal of Psychiatry. 2001 March; 158(3): 498. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11230002&dopt=Abstract
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Gender differences in predictors for long-term smoking cessation following physician advice and nicotine replacement therapy. Author(s): D'Angelo ME, Reid RD, Brown KS, Pipe AL. Source: Canadian Journal of Public Health. Revue Canadienne De Sante Publique. 2001 November-December; 92(6): 418-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11799544&dopt=Abstract
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Gender differences in quit rates following smoking cessation with combination nicotine therapy: influence of baseline smoking behavior. Author(s): Bohadana A, Nilsson F, Rasmussen T, Martinet Y. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2003 February; 5(1): 111-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745512&dopt=Abstract
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Gender differences in response to nicotine replacement therapy: objective and subjective indexes of tobacco withdrawal. Author(s): Wetter DW, Fiore MC, Young TB, McClure JB, de Moor CA, Baker TB. Source: Experimental and Clinical Psychopharmacology. 1999 May; 7(2): 135-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10340153&dopt=Abstract
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Gender differences in tobacco smoking: higher relative exposure to smoke than nicotine in women. Author(s): Zeman MV, Hiraki L, Sellers EM. Source: Journal of Women's Health & Gender-Based Medicine. 2002 March; 11(2): 14753. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11975862&dopt=Abstract
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Genetic influences on smoking behavior and nicotine dependence: a review. Author(s): Yoshimasu K, Kiyohara C. Source: J Epidemiol. 2003 July; 13(4): 183-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12934961&dopt=Abstract
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Genetic polymorphisms in human CYP2A6 gene causing impaired nicotine metabolism. Author(s): Yoshida R, Nakajima M, Watanabe Y, Kwon JT, Yokoi T. Source: British Journal of Clinical Pharmacology. 2002 November; 54(5): 511-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12445030&dopt=Abstract
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Genetic polymorphisms in the cytochrome P450 2A6 (CYP2A6) gene: implications for interindividual differences in nicotine metabolism. Author(s): Oscarson M. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2001 February; 29(2): 91-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11159795&dopt=Abstract
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Genetic variation in CYP2A6-mediated nicotine metabolism alters smoking behavior. Author(s): Tyndale RF, Sellers EM. Source: Therapeutic Drug Monitoring. 2002 February; 24(1): 163-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11805739&dopt=Abstract
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Genetic, environmental, and situational factors mediating the effects of nicotine--an introduction. Author(s): Overstreet DH, Karan L, Rosecrans JA. Source: Behavior Genetics. 1995 March; 25(2): 93-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7733861&dopt=Abstract
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Genotyping of human cytochrome P450 2A6 (CYP2A6), a nicotine C-oxidase. Author(s): Oscarson M, Gullsten H, Rautio A, Bernal ML, Sinues B, Dahl ML, Stengard JH, Pelkonen O, Raunio H, Ingelman-Sundberg M. Source: Febs Letters. 1998 November 6; 438(3): 201-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9827545&dopt=Abstract
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Glycation of the amyloid beta-protein by a nicotine metabolite: a fortuitous chemical dynamic between smoking and Alzheimer's disease. Author(s): Dickerson TJ, Janda KD. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 July 8; 100(14): 8182-7. Epub 2003 June 18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12815102&dopt=Abstract
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Greater sensitivity to subjective effects of nicotine in nonsmokers high in sensation seeking. Author(s): Perkins KA, Gerlach D, Broge M, Grobe JE, Wilson A. Source: Experimental and Clinical Psychopharmacology. 2000 November; 8(4): 462-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11127418&dopt=Abstract
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Green tobacco sickness: occupational nicotine poisoning in tobacco workers. Author(s): Ballard T, Ehlers J, Freund E, Auslander M, Brandt V, Halperin W. Source: Archives of Environmental Health. 1995 September-October; 50(5): 384-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7574894&dopt=Abstract
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Growth factor-mediated mechanisms of nicotine-dependent carcinogenesis. Author(s): Rakowicz-Szulczynska EM, McIntosh DG, Smith M. Source: Carcinogenesis. 1994 September; 15(9): 1839-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7923576&dopt=Abstract
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Guide to nicotine replacement therapies. Breath of fresh air. Author(s): Bryan J. Source: Health Serv J. 2001 May 10; 111(5754): Suppl 34-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11383346&dopt=Abstract
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Hair analysis for nicotine and cotinine: evaluation of extraction procedures, hair treatments, and development of reference material. Author(s): Pichini S, Altieri I, Pellegrini M, Pacifici R, Zuccaro P. Source: Forensic Science International. 1997 January 17; 84(1-3): 243-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9042730&dopt=Abstract
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Hair nicotine concentrations in mothers and children in relation to parental smoking. Author(s): Nafstad P, Jaakkola JJ, Hagen JA, Zahlsen K, Magnus P. Source: Journal of Exposure Analysis and Environmental Epidemiology. 1997 AprilJune; 7(2): 235-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9185014&dopt=Abstract
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Haloperidol reduces smoking of both nicotine-containing and denicotinized cigarettes. Author(s): Brauer LH, Cramblett MJ, Paxton DA, Rose JE. Source: Psychopharmacology. 2001 December; 159(1): 31-7. Epub 2001 September 04. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11797066&dopt=Abstract
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Haplotypes of four novel single nucleotide polymorphisms in the nicotinic acetylcholine receptor beta2-subunit (CHRNB2) gene show no association with smoking initiation or nicotine dependence. Author(s): Silverman MA, Neale MC, Sullivan PF, Harris-Kerr C, Wormley B, Sadek H, Ma Y, Kendler KS, Straub RE. Source: American Journal of Medical Genetics. 2000 October 9; 96(5): 646-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11054772&dopt=Abstract
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Heart attacks, smoking, and the nicotine patch. Author(s): Kafka HP. Source: Annals of Internal Medicine. 1994 September 1; 121(5): 389. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8042844&dopt=Abstract
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Helping older adults become nicotine free. Author(s): Miller CA. Source: Geriatric Nursing (New York, N.Y.). 1996 March-April; 17(2): 96-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8707160&dopt=Abstract
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Hiccups following nicotine gum use. Author(s): Einarson TR, Einarson A. Source: The Annals of Pharmacotherapy. 1997 October; 31(10): 1263-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9337460&dopt=Abstract
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High dose transdermal nicotine therapy for heavy smokers: safety, tolerability and measurement of nicotine and cotinine levels. Author(s): Fredrickson PA, Hurt RD, Lee GM, Wingender L, Croghan IT, Lauger G, Gomez-Dahl L, Offord KP. Source: Psychopharmacology. 1995 December; 122(3): 215-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8748390&dopt=Abstract
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High levels of transdermal nicotine exposure produce green tobacco sickness in Latino farmworkers. Author(s): Arcury TA, Quandt SA, Preisser JS, Bernert JT, Norton D, Wang J. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2003 June; 5(3): 315-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12791526&dopt=Abstract
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High-dose nicotine patch therapy. Percentage of replacement and smoking cessation. Author(s): Dale LC, Hurt RD, Offord KP, Lawson GM, Croghan IT, Schroeder DR. Source: Jama : the Journal of the American Medical Association. 1995 November 1; 274(17): 1353-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7563559&dopt=Abstract
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Higher dosage nicotine patches increase one-year smoking cessation rates: results from the European CEASE trial. Collaborative European Anti-Smoking Evaluation. European Respiratory Society. Author(s): Tonnesen P, Paoletti P, Gustavsson G, Russell MA, Saracci R, Gulsvik A, Rijcken B, Sawe U. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 1999 February; 13(2): 238-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10065662&dopt=Abstract
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High-performance liquid chromatographic assay for N-glucuronidation of nicotine and cotinine in human liver microsomes. Author(s): Nakajima M, Kwon JT, Tanaka E, Yokoi T. Source: Analytical Biochemistry. 2002 March 1; 302(1): 131-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11846386&dopt=Abstract
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Histories of harm reduction: illicit drugs, tobacco, and nicotine. Author(s): Berridge V. Source: Substance Use & Misuse. 1999 January; 34(1): 35-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10052389&dopt=Abstract
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Hits and misses in nicotine psychopharmacology: a personal view of research over a period of 30 years. Author(s): Stolerman I. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2002 November; 4(4): 389-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12528675&dopt=Abstract
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Hospitals vs merchants of nicotine. Author(s): Soffer A. Source: Chest. 2002 August; 122(2): 391-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12171802&dopt=Abstract
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How much does relapse after one year erode effectiveness of smoking cessation treatments? Long-term follow up of randomised trial of nicotine nasal spray. Author(s): Stapleton JA, Sutherland G, Russell MA. Source: Bmj (Clinical Research Ed.). 1998 March 14; 316(7134): 830-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9565457&dopt=Abstract
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Hubble-bubble (water pipe) smoking: levels of nicotine and cotinine in plasma, saliva and urine. Author(s): Shafagoj YA, Mohammed FI, Hadidi KA. Source: Int J Clin Pharmacol Ther. 2002 June; 40(6): 249-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12078938&dopt=Abstract
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Imaging the neurochemistry of nicotine actions: studies with positron emission tomography. Author(s): Volkow ND, Fowler JS, Ding YS, Wang GJ, Gatley SJ. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 1999; 1 Suppl 2: S127-32; Discussion S139-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11768169&dopt=Abstract
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Impact of intravenous nicotine on BOLD signal response to photic stimulation. Author(s): Jacobsen LK, Gore JC, Skudlarski P, Lacadie CM, Jatlow P, Krystal JH. Source: Magnetic Resonance Imaging. 2002 February; 20(2): 141-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12034334&dopt=Abstract
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Impact of messages on concomitant use of nicotine replacement therapy and cigarettes: a randomized trial on the Internet. Author(s): Etter JF, le Houezec J, Landfeldt B. Source: Addiction (Abingdon, England). 2003 July; 98(7): 941-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12814500&dopt=Abstract
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Impact of prior nicotine replacement therapy on smoking cessation efficacy. Author(s): Durcan MJ, White J, Jorenby DE, Fiore MC, Rennard SI, Leischow SJ, Nides MA, Ascher JA, Johnston JA. Source: American Journal of Health Behavior. 2002 May-June; 26(3): 213-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12018757&dopt=Abstract
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Implications for tobacco regulation and public health. Commentary on Stolerman's Inter-species consistency in the behavioural pharmacology of nicotine dependence. Author(s): Henningfield JE. Source: Behavioural Pharmacology. 1999 November; 10(6-7): 581-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10780498&dopt=Abstract
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Implications of nicotine dependence: need for revision of tobacco product regulations. Author(s): Ramstrom LM. Source: Wiener Klinische Wochenschrift. 2003 June 24; 115(11): 401-2; Author Reply 402. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12879739&dopt=Abstract
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Implications of the autonomy theory of nicotine dependence. Author(s): DiFranza JR. Source: Medgenmed [electronic Resource] : Medscape General Medicine. 2002 August 28; 4(3): 8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12466751&dopt=Abstract
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Importance of nonpharmacological factors in nicotine self-administration. Author(s): Caggiula AR, Donny EC, Chaudhri N, Perkins KA, Evans-Martin FF, Sved AF. Source: Physiology & Behavior. 2002 December; 77(4-5): 683-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12527019&dopt=Abstract
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Improved highly sensitive method for determination of nicotine and cotinine in human plasma by high-performance liquid chromatography. Author(s): Nakajima M, Yamamoto T, Kuroiwa Y, Yokoi T. Source: J Chromatogr B Biomed Sci Appl. 2000 May 26; 742(1): 211-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10892601&dopt=Abstract
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Improved incidental memory with nicotine after semantic processing, but not after phonological processing. Author(s): Warburton DM, Skinner A, Martin CD. Source: Psychopharmacology. 2001 January 1; 153(2): 258-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11205428&dopt=Abstract
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In vitro comparative studies of two marketed transdermal nicotine delivery systems: Nicopatch and Nicorette. Author(s): Olivier JC, Rabouan S, Couet W. Source: International Journal of Pharmaceutics. 2003 February 18; 252(1-2): 133-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12550788&dopt=Abstract
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Incorporating nicotine dependence into addiction treatment. Author(s): Rustin TA. Source: Journal of Addictive Diseases : the Official Journal of the Asam, American Society of Addiction Medicine. 1998; 17(1): 83-108. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9549605&dopt=Abstract
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Increased plasma endothelin-1 after nicotine consumption in nonsmokers. Author(s): Letizia C, Cerci S, Subioli S, Scuro L, Clemente G. Source: Clinical Chemistry. 1997 December; 43(12): 2440-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9439476&dopt=Abstract
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Increasing diagnosis of nicotine dependence in adolescent mental health patients. Author(s): Sellman JD, Wootton AR, Stoner DB, Deering DE, Craig BJ. Source: The Australian and New Zealand Journal of Psychiatry. 1999 December; 33(6): 869-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10619214&dopt=Abstract
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Individual differences in nicotine intake per cigarette. Author(s): Patterson F, Benowitz N, Shields P, Kaufmann V, Jepson C, Wileyto P, Kucharski S, Lerman C. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 2003 May; 12(5): 468-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12750245&dopt=Abstract
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Individual differences in preferences for and responses to four nicotine replacement products. Author(s): West R, Hajek P, Nilsson F, Foulds J, May S, Meadows A. Source: Psychopharmacology. 2001 January 1; 153(2): 225-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11205423&dopt=Abstract
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Individual differences in smoking: gender and nicotine addiction. Author(s): Shiffman S, Paton SM. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 1999; 1 Suppl 2: S153-7; Discussion S165-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11768174&dopt=Abstract
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Induction of c-fos expression by nicotine in human periodontal ligament fibroblasts is related to cellular thiol levels. Author(s): Chang YC, Hsieh YS, Lii CK, Huang FM, Tai KW, Chou MY. Source: Journal of Periodontal Research. 2003 February; 38(1): 44-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12558936&dopt=Abstract
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Influence of arterial vs. venous sampling site on nicotine tolerance model selection and parameter estimation. Author(s): Schaedeli F, Pitsiu M, Benowitz NL, Gourlay SG, Verotta D. Source: Journal of Pharmacokinetics and Pharmacodynamics. 2002 February; 29(1): 4966. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12194535&dopt=Abstract
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Inhibition of human cytochrome P450 2E1 by nicotine, cotinine, and aqueous cigarette tar extract in vitro. Author(s): Van Vleet TR, Bombick DW, Coulombe RA Jr. Source: Toxicological Sciences : an Official Journal of the Society of Toxicology. 2001 December; 64(2): 185-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11719700&dopt=Abstract
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Inhibitory effect of Sejin-Eum I/II on nicotine- and cigarette extract-induced cytotoxicity in human lung fibroblast. Author(s): Jin JS, Kim MS, Yi JM, Lee JH, Lee JH, Moon SJ, Jung KP, Lee JK, An NH, Kim HM. Source: Journal of Ethnopharmacology. 2003 May; 86(1): 15-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12686436&dopt=Abstract
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Initial symptoms of nicotine dependence in adolescents. Author(s): DiFranza JR, Rigotti NA, McNeill AD, Ockene JK, Savageau JA, St Cyr D, Coleman M. Source: Tobacco Control. 2000 September; 9(3): 313-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10982576&dopt=Abstract
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Initiation of daily smoking and nicotine dependence in schizophrenia and mood disorders. Author(s): de Leon J, Diaz FJ, Rogers T, Browne D, Dinsmore L. Source: Schizophrenia Research. 2002 July 1; 56(1-2): 47-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12084419&dopt=Abstract
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Intensive smoking cessation counseling versus minimal counseling among hospitalized smokers treated with transdermal nicotine replacement: a randomized trial. Author(s): Simon JA, Carmody TP, Hudes ES, Snyder E, Murray J. Source: The American Journal of Medicine. 2003 May; 114(7): 555-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12753879&dopt=Abstract
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Interactions between alcohol and nicotine dependence: a summary of potential mechanisms and implications for treatment. Author(s): Littleton J, Little H. Source: Alcoholism, Clinical and Experimental Research. 2002 December; 26(12): 1922-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12500121&dopt=Abstract
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Interindividual differences in nicotine metabolism and genetic polymorphisms of human CYP2A6. Author(s): Nakajima M, Kuroiwa Y, Yokoi T. Source: Drug Metabolism Reviews. 2002 November; 34(4): 865-77. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12487152&dopt=Abstract
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Interleukin-8 secretion by cultured oral epidermoid carcinoma cells induced with nicotine and/or arecoline treatments. Author(s): Cheng YA, Shiue LF, Yu HS, Hsieh TY, Tsai CC. Source: Kaohsiung J Med Sci. 2000 March; 16(3): 126-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10846348&dopt=Abstract
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Inter-species consistency in the behavioural pharmacology of nicotine dependence. Author(s): Stolerman IP. Source: Behavioural Pharmacology. 1999 November; 10(6-7): 559-80. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10780497&dopt=Abstract
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Intra-luminal nicotine reduces smooth muscle tone and contractile activity in the distal large bowel. Author(s): Green JT, McKirdy HC, Rhodes J, Thomas GA, Evans BK. Source: European Journal of Gastroenterology & Hepatology. 1999 November; 11(11): 1299-304. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10563544&dopt=Abstract
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Intravenous nicotine and caffeine: subjective and physiological effects in cocaine abusers. Author(s): Garrett BE, Griffiths RR. Source: The Journal of Pharmacology and Experimental Therapeutics. 2001 February; 296(2): 486-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11160635&dopt=Abstract
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Intravenous nicotine reduces cerebral glucose metabolism: a preliminary study. Author(s): Stapleton JM, Gilson SF, Wong DF, Villemagne VL, Dannals RF, Grayson RF, Henningfield JE, London ED. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2003 April; 28(4): 765-72. Epub 2002 November 01. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12655323&dopt=Abstract
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Introduction to tobacco, nicotine, and youth: the tobacco etiology research network. Author(s): Clayton RR, Ries Merikangas K, Abrams DB. Source: Drug and Alcohol Dependence. 2000 May 1; 59 Suppl 1: S1-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10773433&dopt=Abstract
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Investigation of nicotine binding to THP-1 cells: evidence for a non-cholinergic binding site. Author(s): Morgan D, Parsons ME, Whelan CJ. Source: Biochemical Pharmacology. 2001 March 15; 61(6): 733-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11266659&dopt=Abstract
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Involvement of human heat shock protein 90 alpha in nicotine-induced apoptosis. Author(s): Wu YP, Kita K, Suzuki N. Source: International Journal of Cancer. Journal International Du Cancer. 2002 July 1; 100(1): 37-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12115584&dopt=Abstract
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Involvement of serotonin in nicotine dependence: processes relevant to positive and negative regulation of drug intake. Author(s): Olausson P, Engel JA, Soderpalm B. Source: Pharmacology, Biochemistry, and Behavior. 2002 April; 71(4): 757-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11888567&dopt=Abstract
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Is dependence on one drug associated with dependence on other drugs? The cases of alcohol, caffeine and nicotine. Author(s): Hughes JR, Oliveto AH, MacLaughlin M. Source: The American Journal on Addictions / American Academy of Psychiatrists in Alcoholism and Addictions. 2000 Summer; 9(3): 196-201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11000915&dopt=Abstract
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Is it the nicotine or the tobacco? Author(s): Sweanor D. Source: Bulletin of the World Health Organization. 2000; 78(7): 943. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10994270&dopt=Abstract
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Is leptin involved in the acute anorectic effect of nicotine? Author(s): Miyata G, Meguid MM. Source: Nutrition (Burbank, Los Angeles County, Calif.). 2000 February; 16(2): 141-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10696640&dopt=Abstract
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Is nicotine dependence related to smokers' support for restrictions on smoking? Author(s): Lacchetti C, Cohen J, Ashley MJ, Ferrence R, Bull S, de Groh M, Pederson L. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2001 August; 3(3): 257-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11506769&dopt=Abstract
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Is the hair nicotine level a more accurate biomarker of environmental tobacco smoke exposure than urine cotinine? Author(s): Al-Delaimy WK, Crane J, Woodward A. Source: Journal of Epidemiology and Community Health. 2002 January; 56(1): 66-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11801622&dopt=Abstract
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Kicking the habit. Near-sighted on nicotine? Author(s): Huff C. Source: Hospitals & Health Networks / Aha. 1998 October 5; 72(19): 48. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9823283&dopt=Abstract
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Kinetic analysis of regional (S)(-)11C-nicotine binding in normal and Alzheimer brains--in vivo assessment using positron emission tomography. Author(s): Nordberg A, Lundqvist H, Hartvig P, Lilja A, Langstrom B. Source: Alzheimer Disease and Associated Disorders. 1995 Spring; 9(1): 21-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7605618&dopt=Abstract
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Knowledge of health consequences of nicotinism among secondary school pupils. Young people's attitudes towards passive smoking and their opinions about antinicotine act's regulations. Author(s): Zolnierczuk-Kieliszek D. Source: Ann Univ Mariae Curie Sklodowska [med]. 1999; 54: 217-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11205767&dopt=Abstract
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Lack of effect of nicotine or ethanol on the activity of 11beta-hydroxysteroid dehydrogenase type 2. Author(s): Benediktsson R, Magnusdottir EM, Seckl JR. Source: The Journal of Steroid Biochemistry and Molecular Biology. 1997 NovemberDecember; 63(4-6): 303-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9459196&dopt=Abstract
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Lack of effect of transdermal nicotine on 3 cases of primary sclerosing cholangitis. Author(s): Jorgensen G, Waldum HL. Source: Digestive Diseases and Sciences. 1999 December; 44(12): 2484. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10630501&dopt=Abstract
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Lack of efficacy of transdermal nicotine in smoking cessation. Author(s): Joseph AM, Antonnucio DO. Source: The New England Journal of Medicine. 1999 October 7; 341(15): 1157-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10515763&dopt=Abstract
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Late-term smoking cessation despite initial failure: an evaluation of bupropion sustained release, nicotine patch, combination therapy, and placebo. Author(s): Jamerson BD, Nides M, Jorenby DE, Donahue R, Garrett P, Johnston JA, Fiore MC, Rennard SI, Leischow SJ. Source: Clinical Therapeutics. 2001 May; 23(5): 744-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11394732&dopt=Abstract
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Leptin levels in smokers and long-term users of nicotine gum. Author(s): Eliasson B, Smith U. Source: European Journal of Clinical Investigation. 1999 February; 29(2): 145-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10093001&dopt=Abstract
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Let's not overlook nicotine. Author(s): Roll JM, Higgins ST. Source: Journal of Analytical Toxicology. 1996 March-April; 20(2): 143. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8868410&dopt=Abstract
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Levelling the playing field for regulation of nicotine. Author(s): Kawachi I. Source: Bmj (Clinical Research Ed.). 2003 January 18; 326(7381): 115-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12531820&dopt=Abstract
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Levels of cotinine associated with long-term ad-libitum nicotine polacrilex use in a clinical trial. Author(s): Murray RP, Nides MA, Istvan JA, Daniels K. Source: Addictive Behaviors. 1998 July-August; 23(4): 529-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9698981&dopt=Abstract
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Life-time prevalence and risk factors of tobacco/nicotine dependence in male eversmokers in Japan. Author(s): Kawakami N, Takatsuka N, Shimizu H, Takai A. Source: Addiction (Abingdon, England). 1998 July; 93(7): 1023-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9744133&dopt=Abstract
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Longlasting improvement of Tourette's syndrome with transdermal nicotine. Author(s): Dursun SM, Reveley MA, Bird R, Stirton F. Source: Lancet. 1994 December 3; 344(8936): 1577. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7983976&dopt=Abstract
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Long-term effects of a single course of nicotine treatment in acute ulcerative colitis: remission maintenance in a 12-month follow-up study. Author(s): Guslandi M. Source: International Journal of Colorectal Disease. 1999 November; 14(4-5): 261-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10647637&dopt=Abstract
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Long-term effects of nicotine gum on weight gain after smoking cessation. Author(s): Nordstrom BL, Kinnunen T, Utman CH, Garvey AJ. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 1999 September; 1(3): 259-68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11072423&dopt=Abstract
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Long-term effects of the Eclipse cigarette substitute and the nicotine inhaler in smokers not interested in quitting. Author(s): Fagerstrom KO, Hughes JR, Callas PW. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2002; 4 Suppl 2: S141-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12573175&dopt=Abstract
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Long-term use of nicotine chewing gum and mercury exposure from dental amalgam fillings. Author(s): Sallsten G, Thoren J, Barregard L, Schutz A, Skarping G. Source: Journal of Dental Research. 1996 January; 75(1): 594-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8655765&dopt=Abstract
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Long-term use of nicotine gum is associated with hyperinsulinemia and insulin resistance. Author(s): Eliasson B, Taskinen MR, Smith U. Source: Circulation. 1996 September 1; 94(5): 878-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8790020&dopt=Abstract
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Loss of neonatal hypoxia tolerance after prenatal nicotine exposure: implications for sudden infant death syndrome. Author(s): Slotkin TA, Lappi SE, McCook EC, Lorber BA, Seidler FJ. Source: Brain Research Bulletin. 1995; 38(1): 69-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7552377&dopt=Abstract
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L-tyrosine and nicotine induce synthesis of L-Dopa and norepinephrine in human lymphocytes. Author(s): Musso NR, Brenci S, Indiveri F, Lotti G. Source: Journal of Neuroimmunology. 1997 April; 74(1-2): 117-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9119963&dopt=Abstract
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Lung tissue concentrations of nicotine in sudden infant death syndrome (SIDS). Author(s): McMartin KI, Platt MS, Hackman R, Klein J, Smialek JE, Vigorito R, Koren G. Source: The Journal of Pediatrics. 2002 February; 140(2): 205-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11865272&dopt=Abstract
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Malignant potential of palatoglossal, nicotine stomatitis. A study amongst smokers. Author(s): Kurian K, Dayal PK. Source: Indian J Dent Res. 1996 April-June; 7(2): 55-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9495100&dopt=Abstract
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Managing nicotine addiction. Author(s): Kotlyar M, Hatsukami DK. Source: J Dent Educ. 2002 September; 66(9): 1061-73. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12374267&dopt=Abstract
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Managing nicotine dependence. Author(s): Kottke TE. Source: Journal of the American College of Cardiology. 1997 July; 30(1): 131-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9207633&dopt=Abstract
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Maternal nicotine exposure upregulates collagen gene expression in fetal monkey lung. Association with alpha7 nicotinic acetylcholine receptors. Author(s): Sekhon HS, Keller JA, Proskocil BJ, Martin EL, Spindel ER. Source: American Journal of Respiratory Cell and Molecular Biology. 2002 January; 26(1): 31-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11751201&dopt=Abstract
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Maternal smoking during pregnancy and nicotine and cotinine concentrations in maternal and neonatal hair. Author(s): Jacqz-Aigrain E, Zhang D, Maillard G, Luton D, Andre J, Oury JF. Source: Bjog : an International Journal of Obstetrics and Gynaecology. 2002 August; 109(8): 909-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12197371&dopt=Abstract
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Maternal transmission of nicotine dependence: psychiatric, neurocognitive and prenatal factors. Author(s): Niaura R, Bock B, Lloyd EE, Brown R, Lipsitt LP, Buka S. Source: The American Journal on Addictions / American Academy of Psychiatrists in Alcoholism and Addictions. 2001 Winter; 10(1): 16-29. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11268825&dopt=Abstract
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Measurement and analysis of nicotine and other VOCs in indoor air as an indicator of passive smoking. Author(s): Rothberg M, Heloma A, Svinhufvud J, Kahkonen E, Reijula K. Source: The Annals of Occupational Hygiene. 1998 February; 42(2): 129-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9559573&dopt=Abstract
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Measurement of nicotine in hair by reversed-phase high-performance liquid chromatography with electrochemical detection. Author(s): Mahoney GN, Al-Delaimy W. Source: J Chromatogr B Biomed Sci Appl. 2001 April 5; 753(2): 179-87. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11334330&dopt=Abstract
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Measurement of nicotine intake in pregnant women--associations to changes in blood cell count. Author(s): Cope GF, Nayyar P, Holder R. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2001 May; 3(2): 119-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11403725&dopt=Abstract
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Measuring nicotine dependence among high-risk adolescent smokers. Author(s): Prokhorov AV, Pallonen UE, Fava JL, Ding L, Niaura R. Source: Addictive Behaviors. 1996 January-February; 21(1): 117-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8729713&dopt=Abstract
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Measuring nicotine dependence among youth: a review of available approaches and instruments. Author(s): Colby SM, Tiffany ST, Shiffman S, Niaura RS. Source: Drug and Alcohol Dependence. 2000 May 1; 59 Suppl 1: S23-39. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10773436&dopt=Abstract
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Measuring nicotine intake in population surveys: comparability of saliva cotinine and plasma cotinine estimates. Author(s): Jarvis MJ, Primatesta P, Erens B, Feyerabend C, Bryant A. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2003 June; 5(3): 349-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12791530&dopt=Abstract
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Measuring the loss of autonomy over nicotine use in adolescents: the DANDY (Development and Assessment of Nicotine Dependence in Youths) study. Author(s): DiFranza JR, Savageau JA, Fletcher K, Ockene JK, Rigotti NA, McNeill AD, Coleman M, Wood C. Source: Archives of Pediatrics & Adolescent Medicine. 2002 April; 156(4): 397-403. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11929376&dopt=Abstract
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Mecamylamine (a nicotine antagonist) for smoking cessation. Author(s): Cochrane Database Syst Rev. 2001;(2):CD001749 Source: Cochrane Database Syst Rev. 2000; (2): Cd001009. Review. /entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11406005
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Mecamylamine blockade of both positive and negative effects of IV nicotine in human volunteers. Author(s): Lundahl LH, Henningfield JE, Lukas SE. Source: Pharmacology, Biochemistry, and Behavior. 2000 July; 66(3): 637-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10899382&dopt=Abstract
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Mecamylamine combined with nicotine skin patch facilitates smoking cessation beyond nicotine patch treatment alone. Author(s): Rose JE, Behm FM, Westman EC, Levin ED, Stein RM, Ripka GV. Source: Clinical Pharmacology and Therapeutics. 1994 July; 56(1): 86-99. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8033499&dopt=Abstract
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Mecamylamine inhibits nicotine but not capsaicin irritation on the tongue: psychophysical evidence that nicotine and capsaicin activate separate molecular receptors. Author(s): Dessirier JM, O'Mahony M, Sieffermann JM, Carstens E. Source: Neuroscience Letters. 1998 January 9; 240(2): 65-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9486473&dopt=Abstract
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Mechanism of nicotine-evoked release of 3H-noradrenaline in human cerebral cortex slices. Author(s): Woo RS, Park EY, Shin MS, Jeong MS, Zhao RJ, Shin BS, Kim CJ, Park JW, Kim KW. Source: British Journal of Pharmacology. 2002 December; 137(7): 1063-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12429579&dopt=Abstract
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Mechanisms of alcohol-nicotine interactions: alcoholics versus smokers. Author(s): Narahashi T, Soderpalm B, Ericson M, Olausson P, Engel JA, Zhang X, Nordberg A, Marszalec W, Aistrup GL, Schmidt LG, Kalouti U, Smolka And M, Hedlund L. Source: Alcoholism, Clinical and Experimental Research. 2001 May; 25(5 Suppl Isbra): 152S-156S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11391065&dopt=Abstract
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Mechanisms of cytotoxicity of nicotine in human periodontal ligament fibroblast cultures in vitro. Author(s): Chang YC, Huang FM, Tai KW, Yang LC, Chou MY. Source: Journal of Periodontal Research. 2002 August; 37(4): 279-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12200972&dopt=Abstract
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Mechanisms of mitogen-activated protein kinase activation by nicotine in small-cell lung carcinoma cells. Author(s): Cattaneo MG, D'atri F, Vicentini LM. Source: The Biochemical Journal. 1997 December 1; 328 ( Pt 2): 499-503. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9371707&dopt=Abstract
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Melatonin treatment attenuates symptoms of acute nicotine withdrawal in humans. Author(s): Zhdanova IV, Piotrovskaya VR. Source: Pharmacology, Biochemistry, and Behavior. 2000 September; 67(1): 131-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11113492&dopt=Abstract
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Metabolism of nicotine to cotinine studied by a dual stable isotope method. Author(s): Benowitz NL, Jacob P 3rd. Source: Clinical Pharmacology and Therapeutics. 1994 November; 56(5): 483-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7955812&dopt=Abstract
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Methodological considerations in nicotine research: the use of "denicotinised" cigarettes as the control condition in smoking studies. Author(s): Rusted JM, Graupner L, Greenwood K. Source: Psychopharmacology. 1996 May; 125(2): 176-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8783392&dopt=Abstract
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Microarray analysis of nicotine-induced changes in gene expression in endothelial cells. Author(s): Zhang S, Day IN, Ye S. Source: Physiological Genomics. 2001 April 27; 5(4): 187-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11328964&dopt=Abstract
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Microarray technology and its application on nicotine research. Author(s): Li MD, Konu O, Kane JK, Becker KG. Source: Molecular Neurobiology. 2002 June; 25(3): 265-85. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12109875&dopt=Abstract
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Microdialysis in cutaneous pharmacology: kinetic analysis of transdermally delivered nicotine. Author(s): Hegemann L, Forstinger C, Partsch B, Lagler I, Krotz S, Wolff K. Source: The Journal of Investigative Dermatology. 1995 May; 104(5): 839-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7738365&dopt=Abstract
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Microsomal N-glucuronidation of nicotine and cotinine: human hepatic interindividual, human intertissue, and interspecies hepatic variation. Author(s): Ghosheh O, Hawes EM. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2002 December; 30(12): 1478-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12433822&dopt=Abstract
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Minnesota settlement, documents in mind-boggling numbers, smoke-free Birmingham, fire-safe cigarettes, Surgeon General's report, nicotine yields, cigars, Tasmania, and a Marlboro Gear spoof. Author(s): Cannon J. Source: Tobacco Control. 1998 Summer; 7(2): 189-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9789939&dopt=Abstract
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Modeling nicotine arterial-venous differences to predict arterial concentrations and input based on venous measurements: application to smokeless tobacco and nicotine gum. Author(s): Pitsiu M, Gries JM, Benowitz N, Gourlay SG, Verotta D. Source: Journal of Pharmacokinetics and Pharmacodynamics. 2002 August; 29(4): 383402. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12518710&dopt=Abstract
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Molecular and cellular aspects of nicotine abuse. Author(s): Dani JA, Heinemann S. Source: Neuron. 1996 May; 16(5): 905-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8630247&dopt=Abstract
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Molecular mechanisms of the positive reinforcing effect of nicotine. Author(s): Merlo Pich E, Chiamulera C, Carboni L. Source: Behavioural Pharmacology. 1999 November; 10(6-7): 587-96. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10780500&dopt=Abstract
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Molecular orbital calculations and nicotine metabolism: a rationale for experimentally observed metabolite ratios. Author(s): Lewis DF, Gorrod JW. Source: Drug Metabol Drug Interact. 2002; 19(1): 29-39. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12222752&dopt=Abstract
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Mood and physiological effects of subcutaneous nicotine in smokers and neversmokers. Author(s): Foulds J, Stapleton JA, Bell N, Swettenham J, Jarvis MJ, Russell MA. Source: Drug and Alcohol Dependence. 1997 March 14; 44(2-3): 105-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9088782&dopt=Abstract
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Mood management and nicotine gum in smoking treatment: a therapeutic contact and placebo-controlled study. Author(s): Hall SM, Munoz RF, Reus VI, Sees KL, Duncan C, Humfleet GL, Hartz DT. Source: Journal of Consulting and Clinical Psychology. 1996 October; 64(5): 1003-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8916629&dopt=Abstract
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Moving out of the laboratory: does nicotine improve everyday attention? Author(s): Rusted JM, Caulfield D, King L, Goode A. Source: Behavioural Pharmacology. 2000 November; 11(7-8): 621-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11198133&dopt=Abstract
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Multimodal assessment of the effect of chewing gum on nicotine withdrawal. Author(s): Cohen LM, Britt DM, Collins FL, Al'Absi M, McChargue DE. Source: Addictive Behaviors. 2001 March-April; 26(2): 289-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11316385&dopt=Abstract
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Multiple risk factors for the initiation of smoking: the public health imperative for multidisciplinary genetic epidemiological investigations of nicotine addiction. Author(s): Swan GE. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 1999; 1 Suppl 2: S71-3; Discussion S69-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11768190&dopt=Abstract
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Multiple substance dependence: implications for treatment of nicotine dependence. Author(s): West R. Source: Addiction (Abingdon, England). 2001 May; 96(5): 775-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11370642&dopt=Abstract
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Naturalistic, self-assignment comparative trial of bupropion SR, a nicotine patch, or both for smoking cessation treatment in primary care. Author(s): Gold PB, Rubey RN, Harvey RT. Source: The American Journal on Addictions / American Academy of Psychiatrists in Alcoholism and Addictions. 2002 Fall; 11(4): 315-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12584874&dopt=Abstract
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N-glucuronidation of nicotine and cotinine in human: formation of cotinine glucuronide in liver microsomes and lack of catalysis by 10 examined UDPglucuronosyltransferases. Author(s): Ghosheh O, Hawes EM. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2002 September; 30(9): 991-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12167564&dopt=Abstract
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Nicotine addiction, young adults, and smoke-free bars. Author(s): Ling PM, Glantz SA. Source: Drug and Alcohol Review. 2002 June; 21(2): 101-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12188987&dopt=Abstract
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Nicotine and behavioral markers of risk for schizophrenia: a double-blind, placebocontrolled, cross-over study. Author(s): Depatie L, O'Driscoll GA, Holahan AL, Atkinson V, Thavundayil JX, Kin NN, Lal S. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2002 December; 27(6): 1056-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12464463&dopt=Abstract
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Nicotine and familial vulnerability to schizophrenia: a discordant twin study. Author(s): Lyons MJ, Bar JL, Kremen WS, Toomey R, Eisen SA, Goldberg J, Faraone SV, Tsuang M. Source: Journal of Abnormal Psychology. 2002 November; 111(4): 687-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12428784&dopt=Abstract
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Nicotine and neurodegeneration in ageing. Author(s): Zanardi A, Leo G, Biagini G, Zoli M. Source: Toxicology Letters. 2002 February 28; 127(1-3): 207-15. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12052660&dopt=Abstract
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Nicotine and nicotinic receptors; relevance to Parkinson's disease. Author(s): Quik M, Kulak JM. Source: Neurotoxicology. 2002 October; 23(4-5): 581-94. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12428730&dopt=Abstract
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Nicotine as a modulator of behavior: beyond the inverted U. Author(s): Picciotto MR. Source: Trends in Pharmacological Sciences. 2003 September; 24(9): 493-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12967775&dopt=Abstract
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Nicotine concentrations in deciduous teeth and cumulative exposure to tobacco smoke during childhood. Author(s): Garcia-Algar O, Vall O, Segura J, Pascual JA, Diaz D, Mutnoz L, Zuccaro P, Pacifici R, Pichini S. Source: Jama : the Journal of the American Medical Association. 2003 July 9; 290(2): 1967. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12851273&dopt=Abstract
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Nicotine concentrations with concurrent use of cigarettes and nicotine replacement: a review. Author(s): Fagerstrom KO, Hughes JR. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2002; 4 Suppl 2: S73-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12573169&dopt=Abstract
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Nicotine consumption before and during pregnancy affects not only newborn size but also birth modus. Author(s): Kirchengast S, Hartmann B. Source: Journal of Biosocial Science. 2003 April; 35(2): 175-88. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12664956&dopt=Abstract
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Nicotine delivery from smoking bidis and an additive-free cigarette. Author(s): Malson JL, Lee EM, Moolchan ET, Pickworth WB. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2002 November; 4(4): 485-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12521408&dopt=Abstract
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Nicotine dependence and treatment outcome among African American cocainedependent patients. Author(s): Patkar AA, Vergare MJ, Thornton CC, Weinstein SP, Murray HW, Leone FT. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2003 June; 5(3): 411-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12791537&dopt=Abstract
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Nicotine dependence treatment for patients with cancer. Author(s): Cox LS, Africano NL, Tercyak KP, Taylor KL. Source: Cancer. 2003 August 1; 98(3): 632-44. Review. Erratum In: Cancer. 2003 September 1; 98(5): 1104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12879483&dopt=Abstract
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Nicotine dependence: development, mechanisms, individual differences and links to possible neurophysiological correlates. Author(s): Groman E, Fagerstrom K. Source: Wiener Klinische Wochenschrift. 2003 March 31; 115(5-6): 155-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12741073&dopt=Abstract
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Nicotine deprivation effects on the dissociated components of simple reaction time. Author(s): Marzilli TS, Hutcherson AB. Source: Percept Mot Skills. 2002 June; 94(3 Pt 1): 985-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12081303&dopt=Abstract
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Nicotine effects on alertness and spatial attention in non-smokers. Author(s): Griesar WS, Zajdel DP, Oken BS. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2002 May; 4(2): 185-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12028851&dopt=Abstract
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Nicotine exposure and bronchial epithelial cell nicotinic acetylcholine receptor expression in the pathogenesis of lung cancer. Author(s): Minna JD. Source: The Journal of Clinical Investigation. 2003 January; 111(1): 31-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12511585&dopt=Abstract
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Nicotine gum-induced atrial fibrillation. Author(s): Choragudi NL, Aronow WS, DeLuca AJ. Source: Heart Disease. 2003 March-April; 5(2): 100-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12713677&dopt=Abstract
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Nicotine has suppressive effects on dendritic cell function. Author(s): Hogg N. Source: Immunology. 2003 July; 109(3): 329-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12807476&dopt=Abstract
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Nicotine increases oxidative stress, activates NF-kappaB and GRP78, induces apoptosis and sensitizes cells to genotoxic/xenobiotic stresses by a multiple stress inducer, deoxycholate: relevance to colon carcinogenesis. Author(s): Crowley-Weber CL, Dvorakova K, Crowley C, Bernstein H, Bernstein C, Garewal H, Payne CM. Source: Chemico-Biological Interactions. 2003 March 6; 145(1): 53-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12606154&dopt=Abstract
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Nicotine intervention during detoxification and treatment for other substance use. Author(s): Gariti P, Alterman A, Mulvaney F, Mechanic K, Dhopesh V, Yu E, Chychula N, Sacks D. Source: The American Journal of Drug and Alcohol Abuse. 2002 November; 28(4): 671-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12492263&dopt=Abstract
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Nicotine lozenge trial: a "Real-World" perspective. Author(s): Walsh RA. Source: Archives of Internal Medicine. 2002 December 9-23; 162(22): 2632-3; Author Reply 2633. Erratum In: Arch Intern Med. 2003 March 10; 163(5): 571. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12456245&dopt=Abstract
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Nicotine metabolism, human drug metabolism polymorphisms, and smoking behaviour. Author(s): Tricker AR. Source: Toxicology. 2003 February 1; 183(1-3): 151-73. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12504349&dopt=Abstract
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Nicotine modulates the expression of a diverse set of genes in the neuronal SH-SY5Y cell line. Author(s): Dunckley T, Lukas RJ. Source: The Journal of Biological Chemistry. 2003 May 2; 278(18): 15633-40. Epub 2003 February 14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12588870&dopt=Abstract
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Nicotine modulation of in vitro human gingival fibroblast beta1 integrin expression. Author(s): Snyder HB, Caughman G, Lewis J, Billman MA, Schuster G. Source: J Periodontol. 2002 May; 73(5): 505-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12027252&dopt=Abstract
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Nicotine patch therapy based on smoking rate followed by bupropion for prevention of relapse to smoking. Author(s): Hurt RD, Krook JE, Croghan IT, Loprinzi CL, Sloan JA, Novotny PJ, Kardinal CG, Knost JA, Tirona MT, Addo F, Morton RF, Michalak JC, Schaefer PL, Porter PA, Stella PJ. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 March 1; 21(5): 914-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12610193&dopt=Abstract
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Nicotine patches and the subjective effects of cigarette smoking: a pilot study. Author(s): Cardenas L, Busto UE, MacDonald A, Corrigall WA. Source: Can J Clin Pharmacol. 2002 Winter; 9(4): 175-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12584575&dopt=Abstract
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Nicotine permeability across the buccal TR146 cell culture model and porcine buccal mucosa in vitro: effect of pH and concentration. Author(s): Nielsen HM, Rassing MR. Source: European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences. 2002 August; 16(3): 151-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12128169&dopt=Abstract
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Nicotine promotes arteriogenesis. Author(s): Heeschen C, Weis M, Cooke JP. Source: Journal of the American College of Cardiology. 2003 February 5; 41(3): 489-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12575981&dopt=Abstract
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Nicotine reduces the secretion of Alzheimer's beta-amyloid precursor protein containing beta-amyloid peptide in the rat without altering synaptic proteins. Author(s): Lahiri DK, Utsuki T, Chen D, Farlow MR, Shoaib M, Ingram DK, Greig NH. Source: Annals of the New York Academy of Sciences. 2002 June; 965: 364-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12105112&dopt=Abstract
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Nicotine replacement therapy for smoking cessation. Author(s): Silagy C, Lancaster T, Stead L, Mant D, Fowler G. Source: Cochrane Database Syst Rev. 2002; (4): Cd000146. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12519537&dopt=Abstract
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Nicotine replacement therapy in smoking cessation. Author(s): Campbell I. Source: Thorax. 2003 June; 58(6): 464-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12775853&dopt=Abstract
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Nicotine replacement to reduce cigarette consumption in smokers who are unwilling to quit: a randomized trial. Author(s): Etter JF, Laszlo E, Zellweger JP, Perrot C, Perneger TV. Source: Journal of Clinical Psychopharmacology. 2002 October; 22(5): 487-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12352272&dopt=Abstract
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Nicotine strongly activates dendritic cell-mediated adaptive immunity: potential role for progression of atherosclerotic lesions. Author(s): Aicher A, Heeschen C, Mohaupt M, Cooke JP, Zeiher AM, Dimmeler S. Source: Circulation. 2003 February 4; 107(4): 604-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12566374&dopt=Abstract
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Nicotine withdrawal and depressive symptomatology during short-term smoking abstinence: a comparison of postmenopausal women using and not using hormone replacement therapy. Author(s): Allen SS, Hatsukami DK, Christianson D. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2003 February; 5(1): 49-59. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745506&dopt=Abstract
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Nicotine, body weight and potential implications in the treatment of obesity. Author(s): Li MD, Kane JK, Konu O. Source: Current Topics in Medicinal Chemistry. 2003; 3(8): 899-919. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12678839&dopt=Abstract
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Nicotine, serotonin, and sudden infant death syndrome. Author(s): Nattie E, Kinney H. Source: American Journal of Respiratory and Critical Care Medicine. 2002 December 15; 166(12 Pt 1): 1530-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12471066&dopt=Abstract
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Nicotine-induced angiogenesis. Author(s): Schwartz MA. Source: The Journal of Clinical Psychiatry. 2002 October; 63(10): 949-50; Author Reply 950. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12416607&dopt=Abstract
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Nicotine-induced Ca2+ signaling and down-regulation of nicotinic acetylcholine receptor subunit expression in the CEM human leukemic T-cell line. Author(s): Kimura R, Ushiyama N, Fujii T, Kawashima K. Source: Life Sciences. 2003 March 28; 72(18-19): 2155-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12628473&dopt=Abstract
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Objective measurements of nicotine exposure in victims of sudden infant death syndrome and in other unexpected child deaths. Author(s): Milerad J, Vege A, Opdal SH, Rognum TO. Source: The Journal of Pediatrics. 1998 August; 133(2): 232-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9709711&dopt=Abstract
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Olfactory thresholds for nicotine and menthol in smokers (abstinent and nonabstinent) and nonsmokers. Author(s): Rosenblatt MR, Olmstead RE, Iwamoto-Schaap PN, Jarvik ME. Source: Physiology & Behavior. 1998 December 1; 65(3): 575-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9877426&dopt=Abstract
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Onset of major depression during treatment for nicotine dependence. Author(s): Killen JD, Fortmann SP, Schatzberg A, Hayward C, Varady A. Source: Addictive Behaviors. 2003 April; 28(3): 461-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12628619&dopt=Abstract
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Open randomised trial of intermittent very low energy diet together with nicotine gum for stopping smoking in women who gained weight in previous attempts to quit. Author(s): Danielsson T, Rossner S, Westin A. Source: Bmj (Clinical Research Ed.). 1999 August 21; 319(7208): 490-3; Discussion 494. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10454403&dopt=Abstract
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Opioids induce while nicotine suppresses apoptosis in human lung cancer cells. Author(s): Maneckjee R, Minna JD. Source: Cell Growth & Differentiation : the Molecular Biology Journal of the American Association for Cancer Research. 1994 October; 5(10): 1033-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7848904&dopt=Abstract
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Opioids suppress basal and nicotine-induced catecholamine secretion via a stabilizing effect on actin filaments. Author(s): Dermitzaki E, Gravanis A, Venihaki M, Stournaras C, Margioris AN. Source: Endocrinology. 2001 May; 142(5): 2022-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11316769&dopt=Abstract
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Oral caffeine maintenance potentiates the reinforcing and stimulant subjective effects of intravenous nicotine in cigarette smokers. Author(s): Jones HE, Griffiths RR. Source: Psychopharmacology. 2003 January; 165(3): 280-90. Epub 2002 November 14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12434259&dopt=Abstract
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Oral irritant effects of nicotine. Psychophysical evidence for decreased sensation following repeated application of and lack of cross-desensitization to capsaicin. Author(s): Dessirier JM, O'Mahony M, Carstens E. Source: Annals of the New York Academy of Sciences. 1998 November 30; 855: 828-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9929695&dopt=Abstract
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Oral irritant effects of nicotine: psychophysical evidence for decreased sensation following repeated application and lack of cross-desensitization to capsaicin. Author(s): Dessirier JM, O'Mahony M, Carstens E. Source: Chemical Senses. 1997 October; 22(5): 483-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9363348&dopt=Abstract
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Oral irritant properties of menthol: sensitizing and desensitizing effects of repeated application and cross-desensitization to nicotine. Author(s): Dessirier JM, O'Mahony M, Carstens E. Source: Physiology & Behavior. 2001 May; 73(1-2): 25-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11399291&dopt=Abstract
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Oral irritant properties of piperine and nicotine: psychophysical evidence for asymmetrical desensitization effects. Author(s): Dessirier JM, Nguyen N, Sieffermann JM, Carstens E, O'Mahony M. Source: Chemical Senses. 1999 August; 24(4): 405-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10480676&dopt=Abstract
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Oral nicotine in treatment of primary sclerosing cholangitis: a pilot study. Author(s): Angulo P, Bharucha AE, Jorgensen RA, DeSotel CK, Sandborn WJ, Larusso NF, Lindor KD. Source: Digestive Diseases and Sciences. 1999 March; 44(3): 602-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10080157&dopt=Abstract
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Oral nicotine solution for smoking cessation: a pilot tolerability study. Author(s): Westman EC, Tomlin KF, Perkins CE, Rose JE. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2001 November; 3(4): 391-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11694207&dopt=Abstract
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OTC nicotine gum. Author(s): McKenna JP. Source: The Journal of Family Practice. 1995 January; 40(1): 16; Author Reply 16-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7807029&dopt=Abstract
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OTC nicotine gum. Author(s): Glover ED. Source: The Journal of Family Practice. 1995 January; 40(1): 15-6; Author Reply 16-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7807028&dopt=Abstract
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Outcome of ulcerative colitis after treatment with transdermal nicotine. Author(s): Guslandi M, Tittobello A. Source: European Journal of Gastroenterology & Hepatology. 1998 June; 10(6): 513-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9855069&dopt=Abstract
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Overcoming barriers to nicotine dependence treatment. Author(s): Ferry LH. Source: Primary Care. 1999 September; 26(3): 707-46. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10436295&dopt=Abstract
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Over-the-counter nicotine patch therapy for smoking cessation: results from randomized, double-blind, placebo-controlled, and open label trials. Author(s): Hays JT, Croghan IT, Schroeder DR, Offord KP, Hurt RD, Wolter TD, Nides MA, Davidson M. Source: American Journal of Public Health. 1999 November; 89(11): 1701-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10553392&dopt=Abstract
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Pain inhibition, nicotine, and gender. Author(s): Jamner LD, Girdler SS, Shapiro D, Jarvik ME. Source: Experimental and Clinical Psychopharmacology. 1998 February; 6(1): 96-106. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9526150&dopt=Abstract
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Passive exposure to tobacco smoke: hair nicotine levels in preschool children. Author(s): Kalinic N, Skender Lj, Karacic V, Brcic I, Vadjic V. Source: Bulletin of Environmental Contamination and Toxicology. 2003 July; 71(1): 1-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12945833&dopt=Abstract
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Pathological mutations of nicotinic receptors and nicotine-based therapies for brain disorders. Author(s): Lena C, Changeux JP. Source: Current Opinion in Neurobiology. 1997 October; 7(5): 674-82. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9384554&dopt=Abstract
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Pathophysiological effects of nicotine on the pancreas: an update. Author(s): Chowdhury P, MacLeod S, Udupa KB, Rayford PL. Source: Experimental Biology and Medicine (Maywood, N.J.). 2002 July; 227(7): 445-54. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12094008&dopt=Abstract
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Peculiar vulnerability to nicotine oral self-administration in mice during early adolescence. Author(s): Adriani W, Macri S, Pacifici R, Laviola G. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2002 August; 27(2): 212-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12093595&dopt=Abstract
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Persistence of cigarette smoking: familial liability and the role of nicotine dependence. Author(s): Johnson EO, Chase GA, Breslau N. Source: Addiction (Abingdon, England). 2002 August; 97(8): 1063-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12144609&dopt=Abstract
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Persistent and delayed behavioral changes after nicotine treatment in adolescent rats. Author(s): Trauth JA, Seidler FJ, Slotkin TA. Source: Brain Research. 2000 October 13; 880(1-2): 167-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11033001&dopt=Abstract
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Personal exposure to environmental tobacco smoke: salivary cotinine, airborne nicotine, and nonsmoker misclassification. Author(s): Jenkins RA, Counts RW. Source: Journal of Exposure Analysis and Environmental Epidemiology. 1999 JulyAugust; 9(4): 352-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10489160&dopt=Abstract
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PET studies of the influences of nicotine on neural systems in cigarette smokers. Author(s): Rose JE, Behm FM, Westman EC, Mathew RJ, London ED, Hawk TC, Turkington TG, Coleman RE. Source: The American Journal of Psychiatry. 2003 February; 160(2): 323-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12562580&dopt=Abstract
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Pharmacokinetic investigation of a nicotine sublingual tablet. Author(s): Molander L, Lunell E. Source: European Journal of Clinical Pharmacology. 2001 January-February; 56(11): 8139. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11294371&dopt=Abstract
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Pharmacokinetics of nicotine in healthy elderly people. Author(s): Molander L, Hansson A, Lunell E. Source: Clinical Pharmacology and Therapeutics. 2001 January; 69(1): 57-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11180039&dopt=Abstract
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Pharmacokinetics of nicotine in kidney failure. Author(s): Molander L, Hansson A, Lunell E, Alainentalo L, Hoffmann M, Larsson R. Source: Clinical Pharmacology and Therapeutics. 2000 September; 68(3): 250-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11014406&dopt=Abstract
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Pharmacologic therapy for nicotine addiction. Author(s): DeGraff AC Jr. Source: Chest. 2002 August; 122(2): 392-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12171803&dopt=Abstract
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Pharmacology of neuronal nicotinic acetylcholine recceptors: effects of acute and chronic nicotine. Author(s): Kellar KJ, Davila-Garcia MI, Xiao Y. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 1999; 1 Suppl 2: S117-20; Discussion S139-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11768167&dopt=Abstract
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Pharmacotherapy of nicotine dependence. Author(s): Haustein KO. Source: Int J Clin Pharmacol Ther. 2000 June; 38(6): 273-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10890576&dopt=Abstract
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Plasma leptin concentrations and lipid profiles during nicotine abstinence. Author(s): Oeser A, Goffaux J, Snead W, Carlson MG. Source: The American Journal of the Medical Sciences. 1999 September; 318(3): 152-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10487405&dopt=Abstract
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Posttraumatic stress disorder and the incidence of nicotine, alcohol, and other drug disorders in persons who have experienced trauma. Author(s): Breslau N, Davis GC, Schultz LR. Source: Archives of General Psychiatry. 2003 March; 60(3): 289-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12622662&dopt=Abstract
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Potentiation of nicotine reward by alcohol. Author(s): Rose JE, Brauer LH, Behm FM, Cramblett M, Calkins K, Lawhon D. Source: Alcoholism, Clinical and Experimental Research. 2002 December; 26(12): 1930-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12500124&dopt=Abstract
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Predicting smoking cessation and major depression in nicotine-dependent smokers. Author(s): Breslau N, Johnson EO. Source: American Journal of Public Health. 2000 July; 90(7): 1122-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10897192&dopt=Abstract
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Pregnancy categories of nicotine replacement products. Author(s): Lyman AE Jr, Raebal MA. Source: The Annals of Pharmacotherapy. 2001 November; 35(11): 1496-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11724111&dopt=Abstract
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Prenatal effects of maternal smoking on daughters' smoking: nicotine or testosterone exposure? Author(s): Kandel DB, Udry JR. Source: American Journal of Public Health. 1999 September; 89(9): 1377-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10474556&dopt=Abstract
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Prenatal exposure to nicotine impairs protective responses of rat pups to hypoxia in an age-dependent manner. Author(s): Fewell JE, Smith FG, Ng VK. Source: Respiration Physiology. 2001 August; 127(1): 61-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11445201&dopt=Abstract
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Prenatal nicotine alters vigilance states and AchR gene expression in the neonatal rat: implications for SIDS. Author(s): Frank MG, Srere H, Ledezma C, O'Hara B, Heller HC. Source: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 2001 April; 280(4): R1134-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11247836&dopt=Abstract
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Prenatal nicotine exposure alters pulmonary function in newborn rhesus monkeys. Author(s): Sekhon HS, Keller JA, Benowitz NL, Spindel ER. Source: American Journal of Respiratory and Critical Care Medicine. 2001 September 15; 164(6): 989-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11587984&dopt=Abstract
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Prenatal nicotine exposure and abnormal lung function. Author(s): Pierce RA, Nguyen NM. Source: American Journal of Respiratory Cell and Molecular Biology. 2002 January; 26(1): 10-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11751198&dopt=Abstract
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Prescription of transdermal nicotine patches for smoking cessation in general practice: evaluation of cost-effectiveness. Author(s): Stapleton JA, Lowin A, Russell MA. Source: Lancet. 1999 July 17; 354(9174): 210-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10421303&dopt=Abstract
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Prevalence of nicotine consumption in drug deaths. Author(s): Hafezi M, Bohnert M, Weinmann W, Pollak S. Source: Forensic Science International. 2001 July 15; 119(3): 284-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11390141&dopt=Abstract
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Prevalence of smokers and nicotine-addicted patients in a suburban emergency department. Author(s): Richman PB, Dinowitz S, Nashed A, Eskin B, Cody R. Source: Academic Emergency Medicine : Official Journal of the Society for Academic Emergency Medicine. 1999 August; 6(8): 807-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10463552&dopt=Abstract
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Prevention of lung cancer by long-term use of alternative nicotine delivery systems? Author(s): Kunze U, Schmeiser-Rieder A, Schoberberger R. Source: European Journal of Cancer (Oxford, England : 1990). 1999 February; 35(2): 1956. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10448258&dopt=Abstract
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Probabilities of alcohol high-risk drinking, abuse or dependence estimated on grounds of tobacco smoking and nicotine dependence. Author(s): John U, Meyer C, Rumpf HJ, Hapke U. Source: Addiction (Abingdon, England). 2003 June; 98(6): 805-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12780369&dopt=Abstract
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Proceedings of the satellite symposium on nicotine and alcohol of the 10th Congress of the International Society for Biomedical Research on Alcoholism. Yokohama, Japan, July 8, 2000. Author(s): Cochrane Database Syst Rev. 2002;(4):CD000146 Source: Alcohol (Fayetteville, N.Y.). 2001 June; 24(2): 61-139. /entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12519537
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Production of endothelin by cultured human endothelial cells following exposure to nicotine or caffeine. Author(s): Lee WO, Wright SM. Source: Metabolism: Clinical and Experimental. 1999 July; 48(7): 845-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10421223&dopt=Abstract
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Progress in nicotine and tobacco research. Author(s): Eissenberg T. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2002 August; 4(3): 355-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12215245&dopt=Abstract
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Prolonged nicotine patch use in quitters with past abstinence-induced depressed mood. Author(s): Pomerleau OF, Pomerleau CS, Marks JL, Snedecor SM, Mehringer AM, Namenek Brouwer RJ, Saules KK. Source: Journal of Substance Abuse Treatment. 2003 January; 24(1): 13-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12646326&dopt=Abstract
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Protease activity induced by nicotine in human cells. Author(s): Wang XL, Kita K, Takahashi S, Hasegawa R, Chi XJ, Yamamori H, Nakajima N, Yokoe H, Tanzawa H, Suzuki N. Source: International Journal of Molecular Medicine. 1999 November; 4(5): 537-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10534577&dopt=Abstract
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Psychoactive drugs and pilot performance: a comparison of nicotine, donepezil, and alcohol effects. Author(s): Mumenthaler MS, Yesavage JA, Taylor JL, O'Hara R, Friedman L, Lee H, Kraemer HC. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2003 July; 28(7): 1366-73. Epub 2003 May 14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12784106&dopt=Abstract
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Psychological functions served by nicotine chewing gum. Author(s): Parrott AC, Craig D. Source: Addictive Behaviors. 1995 May-June; 20(3): 271-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7653311&dopt=Abstract
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Psychophysiological effects of nicotine abstinence and behavioral challenges in habitual smokers. Author(s): al'Absi M, Amunrud T, Wittmers LE. Source: Pharmacology, Biochemistry, and Behavior. 2002 June; 72(3): 707-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12175468&dopt=Abstract
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Psychosocial correlates of nicotine dependence among men and women in the U.S. naval services. Author(s): Hourani LL, Yuan H, Bray RM, Vincus AA. Source: Addictive Behaviors. 1999 July-August; 24(4): 521-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10466847&dopt=Abstract
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Psychosocial versus nicotine-only self-report measures for predicting follow-up smoking status. Author(s): McCarthy WJ, Zhou Y, Hser YI. Source: Journal of Behavioral Medicine. 2001 February; 24(1): 75-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11296471&dopt=Abstract
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Quantitation of 4-oxo-4-(3-pyridyl)butanoic acid and enantiomers of 4-hydroxy-4-(3pyridyl)butanoic acid in human urine: A substantial pathway of nicotine metabolism. Author(s): Hecht SS, Hatsukami DK, Bonilla LE, Hochalter JB. Source: Chemical Research in Toxicology. 1999 February; 12(2): 172-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10027795&dopt=Abstract
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Quantitative EEG effects of nicotine replacement by cigarette smoking. Author(s): Newton TF, Cook IA, Holschneider DP, Rosenblatt MR, Lindholm JE, Jarvik MM. Source: Neuropsychobiology. 1998; 37(2): 112-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9566277&dopt=Abstract
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Quitting chew: results from a randomized trial using nicotine patches. Author(s): Howard-Pitney B, Killen JD, Fortmann SP. Source: Experimental and Clinical Psychopharmacology. 1999 November; 7(4): 362-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10609971&dopt=Abstract
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Quitting cigarette smoking produces minimal loss of chronic tolerance to nicotine. Author(s): Perkins KA, Gerlach D, Broge M, Sanders M, Grobe J, Fonte C, Cherry C, Wilson A, Jacob R. Source: Psychopharmacology. 2001 October; 158(1): 7-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11685379&dopt=Abstract
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Randomised trial investigating effect of a novel nicotine delivery device (Eclipse) and a nicotine oral inhaler on smoking behaviour, nicotine and carbon monoxide exposure, and motivation to quit. Author(s): Fagerstrom KO, Hughes JR, Rasmussen T, Callas PW. Source: Tobacco Control. 2000 September; 9(3): 327-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10982578&dopt=Abstract
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Randomized comparative trial of nicotine polacrilex, a transdermal patch, nasal spray, and an inhaler. Author(s): Hajek P, West R, Foulds J, Nilsson F, Burrows S, Meadow A. Source: Archives of Internal Medicine. 1999 September 27; 159(17): 2033-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10510989&dopt=Abstract
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Randomized trial of acupuncture for nicotine withdrawal symptoms. Author(s): White AR, Resch KL, Ernst E. Source: Archives of Internal Medicine. 1998 November 9; 158(20): 2251-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9818805&dopt=Abstract
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Randomized, double-blind, placebo-controlled study of transdermal nicotine patch for smoking cessation. Author(s): Perng RP, Hsieh WC, Chen YM, Lu CC, Chiang SJ. Source: J Formos Med Assoc. 1998 August; 97(8): 547-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9747065&dopt=Abstract
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Rapid Akt activation by nicotine and a tobacco carcinogen modulates the phenotype of normal human airway epithelial cells. Author(s): West KA, Brognard J, Clark AS, Linnoila IR, Yang X, Swain SM, Harris C, Belinsky S, Dennis PA. Source: The Journal of Clinical Investigation. 2003 January; 111(1): 81-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12511591&dopt=Abstract
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Rapid and sensitive high-performance liquid chromatographic determination of nicotine and cotinine in nonsmoker human and rat urines. Author(s): Oddoze C, Pauli AM, Pastor J. Source: J Chromatogr B Biomed Sci Appl. 1998 April 24; 708(1-2): 95-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9653951&dopt=Abstract
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Rapid method for the simultaneous measurement of nicotine and cotinine in urine and serum by gas chromatography-mass spectrometry. Author(s): James H, Tizabi Y, Taylor R. Source: J Chromatogr B Biomed Sci Appl. 1998 April 24; 708(1-2): 87-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9653950&dopt=Abstract
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Rapid solid-phase extraction method for automated gas chromatographic-mass spectrometric determination of nicotine in plasma. Author(s): Davoli E, Stramare L, Fanelli R, Diomede L, Salmona M. Source: J Chromatogr B Biomed Sci Appl. 1998 April 10; 707(1-2): 312-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9613965&dopt=Abstract
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Rationale for cigarette smoking and for mentholation preference in cocaine- and nicotine-dependent outpatients. Author(s): Wiseman EJ, McMillan DE. Source: Comprehensive Psychiatry. 1998 November-December; 39(6): 358-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9829143&dopt=Abstract
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Rationale for treating pregnant smokers with nicotine patches. Author(s): Scalera A, Koren G. Source: Can Fam Physician. 1998 August; 44: 1601-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9721411&dopt=Abstract
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Re: Cost-effectiveness of the nicotine transdermal patch. Author(s): Stapleton J. Source: Preventive Medicine. 1998 March-April; 27(2): 304-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9579011&dopt=Abstract
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Real-world efficacy of prescription and over-the-counter nicotine replacement therapy. Author(s): Shiffman S, Rolf CN, Hellebusch SJ, Gorsline J, Gorodetzky CW, Chiang YK, Schleusener DS, Di Marino ME. Source: Addiction (Abingdon, England). 2002 May; 97(5): 505-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12033652&dopt=Abstract
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Receptor-mediated action of nicotine in human skin. Author(s): Grando SA. Source: International Journal of Dermatology. 2001 November; 40(11): 691-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11737434&dopt=Abstract
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Receptor-mediated inhibition of keratinocyte migration by nicotine involves modulations of calcium influx and intracellular concentration. Author(s): Zia S, Ndoye A, Lee TX, Webber RJ, Grando SA. Source: The Journal of Pharmacology and Experimental Therapeutics. 2000 June; 293(3): 973-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10869400&dopt=Abstract
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Recommendations for the treatment of nicotine dependency. Author(s): Montalto NJ. Source: J Am Osteopath Assoc. 2002 June; 102(6): 342-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12090652&dopt=Abstract
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Reducing toxicity exposure for the nicotine-dependent. Author(s): Sweanor D. Source: Addiction (Abingdon, England). 2003 September; 98(9): 1197-8; Discussion 12047. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12930203&dopt=Abstract
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Reference interval and subject variation in excretion of urinary metabolites of nicotine from non-smoking healthy subjects in Denmark. Author(s): Hansen AM, Garde AH, Christensen JM, Eller N, Knudsen LE, HeinrichRamm R. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 2001 February; 304(1-2): 125-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11165207&dopt=Abstract
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Regional cerebral blood flow effects of nicotine in overnight abstinent smokers. Author(s): Zubieta J, Lombardi U, Minoshima S, Guthrie S, Ni L, Ohl LE, Koeppe RA, Domino EF. Source: Biological Psychiatry. 2001 June 1; 49(11): 906-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11377408&dopt=Abstract
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Regulation of cytokine production in human gingival fibroblasts following treatment with nicotine and lipopolysaccharide. Author(s): Wendell KJ, Stein SH. Source: J Periodontol. 2001 August; 72(8): 1038-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11525435&dopt=Abstract
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Regulation of feeding-associated peptides and receptors by nicotine. Author(s): Li MD, Parker SL, Kane JK. Source: Molecular Neurobiology. 2000 August-December; 22(1-3): 143-65. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11414277&dopt=Abstract
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Regulation of nicotine replacement therapies (NRT): a critique of current practice. Author(s): McNeill A, Foulds J, Bates C. Source: Addiction (Abingdon, England). 2001 December; 96(12): 1757-68. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11784468&dopt=Abstract
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Regulation of nicotinic acetylcholine receptor numbers and function by chronic nicotine exposure. Author(s): Gentry CL, Lukas RJ. Source: Current Drug Targets. Cns and Neurological Disorders. 2002 August; 1(4): 35985. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12769610&dopt=Abstract
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Regulatory imbalance between medicinal and non-medicinal nicotine. Author(s): Sweanor D. Source: Addiction (Abingdon, England). 2000 January; 95 Suppl 1: S25-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10723819&dopt=Abstract
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Reinforcing effects of nicotine as a function of smoking status. Author(s): Perkins KA, Gerlach D, Broge M, Fonte C, Wilson A. Source: Experimental and Clinical Psychopharmacology. 2001 August; 9(3): 243-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11534534&dopt=Abstract
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Relationship between indoor nicotine concentrations, time-activity data, and urine cotinine-creatinine ratios in evaluating children's exposure to environmental tobacco smoke. Author(s): Chan CC, Chen SC, Wang JD. Source: Archives of Environmental Health. 1995 May-June; 50(3): 230-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7618956&dopt=Abstract
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Relationship between interindividual differences in nicotine metabolism and CYP2A6 genetic polymorphism in humans. Author(s): Nakajima M, Kwon JT, Tanaka N, Zenta T, Yamamoto Y, Yamamoto H, Yamazaki H, Yamamoto T, Kuroiwa Y, Yokoi T. Source: Clinical Pharmacology and Therapeutics. 2001 January; 69(1): 72-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11180041&dopt=Abstract
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Relationship between mood improvement and sleep changes with acute nicotine administration in non-smoking major depressed patients. Author(s): Salin-Pascual RJ. Source: Revista De Investigacion Clinica; Organo Del Hospital De Enfermedades De La Nutricion. 2002 January-February; 54(1): 36-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11995405&dopt=Abstract
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Relationship of ADHD, depression, and non-tobacco substance use disorders to nicotine dependence in substance-dependent delinquents. Author(s): Riggs PD, Mikulich SK, Whitmore EA, Crowley TJ. Source: Drug and Alcohol Dependence. 1999 May 3; 54(3): 195-205. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10372793&dopt=Abstract
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Relationships between sensation seeking and emotional symptomatology during smoking cessation with nicotine patch therapy. Author(s): Carton S, Le Houezec J, Lagrue G, Jouvent R. Source: Addictive Behaviors. 2000 September-October; 25(5): 653-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11023009&dopt=Abstract
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Reliability of selected measures of nicotine dependence among adolescents. Author(s): O'Loughlin J, Tarasuk J, Difranza J, Paradis G. Source: Annals of Epidemiology. 2002 July; 12(5): 353-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12062924&dopt=Abstract
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Research into smoking or nicotine and human cognitive performance: does the source of funding make a difference? Author(s): Turner C, Spilich GJ. Source: Addiction (Abingdon, England). 1997 November; 92(11): 1423-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9519485&dopt=Abstract
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Residential (inpatient) treatment compared with outpatient treatment for nicotine dependence. Author(s): Hays JT, Wolter TD, Eberman KM, Croghan IT, Offord KP, Hurt RD. Source: Mayo Clinic Proceedings. 2001 February; 76(2): 124-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11213299&dopt=Abstract
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Respiratory suppression induced by nicotine withdrawal in the neonatal rat brainstem: implications in the SIDS risk factor. Author(s): Okada Y, Kuwana S, Iwanami M. Source: Advances in Experimental Medicine and Biology. 2001; 499: 187-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11729876&dopt=Abstract
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Response of the hypothalamo-pituitary-adrenal axis to nicotine. Author(s): Matta SG, Fu Y, Valentine JD, Sharp BM. Source: Psychoneuroendocrinology. 1998 February; 23(2): 103-13. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9621392&dopt=Abstract
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Response to nicotine dependence treatment in smokers with current and past alcohol problems. Author(s): Hays JT, Schroeder DR, Offord KP, Croghan IT, Patten CA, Hurt RD, Jorenby DE, Fiore MC. Source: Annals of Behavioral Medicine : a Publication of the Society of Behavioral Medicine. 1999 Summer; 21(3): 244-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10626032&dopt=Abstract
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Review of the evidence that pH is a determinant of nicotine dosage from oral use of smokeless tobacco. Author(s): Tomar SL, Henningfield JE. Source: Tobacco Control. 1997 Autumn; 6(3): 219-25. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9396107&dopt=Abstract
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Risk of acute first myocardial infarction and use of nicotine patches in a general population. Author(s): Kimmel SE, Berlin JA, Miles C, Jaskowiak J, Carson JL, Strom BL. Source: Journal of the American College of Cardiology. 2001 April; 37(5): 1297-302. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11300438&dopt=Abstract
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Role of alpha7 nicotinic receptors in nicotine dependence and implications for psychiatric illness. Author(s): Nomikos GG, Schilstrom B, Hildebrand BE, Panagis G, Grenhoff J, Svensson TH. Source: Behavioural Brain Research. 2000 August; 113(1-2): 97-103. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10942036&dopt=Abstract
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Role of dopamine in the behavioural actions of nicotine related to addiction. Author(s): Di Chiara G. Source: European Journal of Pharmacology. 2000 March 30; 393(1-3): 295-314. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10771025&dopt=Abstract
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Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Author(s): Yamazaki H, Inoue K, Hashimoto M, Shimada T. Source: Archives of Toxicology. 1999 March; 73(2): 65-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10350185&dopt=Abstract
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Safety of nicotine in smokers with hypertension. Author(s): Benowitz NL. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 2001 July; 14(7 Pt 1): 731-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11465662&dopt=Abstract
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Sensation seeking, puberty, and nicotine, alcohol, and marijuana use in adolescence. Author(s): Martin CA, Kelly TH, Rayens MK, Brogli BR, Brenzel A, Smith WJ, Omar HA. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2002 December; 41(12): 1495-502. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12447037&dopt=Abstract
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Sensitive and simple method for the determination of nicotine and cotinine in human urine, plasma and saliva by gas chromatography-mass spectrometry. Author(s): Shin HS, Kim JG, Shin YJ, Jee SH. Source: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences. 2002 March 25; 769(1): 177-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11936690&dopt=Abstract
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Sensitivity of nicotine-containing and de-nicotinized cigarette consumption to alternative non-drug reinforcement: a behavioral economic analysis. Author(s): Shahan TA, Bickel WK, Badger GJ, Giordano LA. Source: Behavioural Pharmacology. 2001 July; 12(4): 277-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11548113&dopt=Abstract
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Sensory and physiologic effects of menthol and non-menthol cigarettes with differing nicotine delivery. Author(s): Pickworth WB, Moolchan ET, Berlin I, Murty R. Source: Pharmacology, Biochemistry, and Behavior. 2002 January-February; 71(1-2): 5561. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11812507&dopt=Abstract
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Sex differences in brain and behavior: emphasis on nicotine, nitric oxide and place learning. Author(s): Pogun S. Source: International Journal of Psychophysiology : Official Journal of the International Organization of Psychophysiology. 2001 October; 42(2): 195-208. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11587776&dopt=Abstract
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Sex differences in the subjective and reinforcing effects of cigarette nicotine dose. Author(s): Perkins KA, Jacobs L, Sanders M, Caggiula AR. Source: Psychopharmacology. 2002 September; 163(2): 194-201. Epub 2002 July 13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12202966&dopt=Abstract
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Shed king cobra and cobra skins as model membranes for in-vitro nicotine permeation studies. Author(s): Pongjanyakul T, Prakongpan S, Panomsuk S, Puttipipatkhachorn S, Priprem A. Source: The Journal of Pharmacy and Pharmacology. 2002 October; 54(10): 1345-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12396295&dopt=Abstract
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Short-term effects of smoking and nicotine chewing gum on endothelium-dependent vasodilation in young healthy habitual smokers. Author(s): Sarabi M, Lind L. Source: Journal of Cardiovascular Pharmacology. 2000 March; 35(3): 451-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10710132&dopt=Abstract
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Short-term effects of transdermal nicotine on acute tissue plasminogen activator release in vivo in man. Author(s): Pellegrini MP, Newby DE, Maxwell S, Webb DJ. Source: Cardiovascular Research. 2001 November; 52(2): 321-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11684081&dopt=Abstract
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Should the FDA regulate nicotine-containing cigarettes? Has the Agency established a legal basis and, if not, should congress grant it? Author(s): Carchman SH. Source: Food Drug Law J. 1996; 51(1): 85-138. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11794355&dopt=Abstract
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Simultaneous analysis of nicotine, nicotine metabolites, and tobacco alkaloids in serum or urine by tandem mass spectrometry, with clinically relevant metabolic profiles. Author(s): Moyer TP, Charlson JR, Enger RJ, Dale LC, Ebbert JO, Schroeder DR, Hurt RD. Source: Clinical Chemistry. 2002 September; 48(9): 1460-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12194923&dopt=Abstract
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Simultaneous determination of nicotine and eight nicotine metabolites in urine of smokers using liquid chromatography-tandem mass spectrometry. Author(s): Meger M, Meger-Kossien I, Schuler-Metz A, Janket D, Scherer G. Source: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences. 2002 October 5; 778(1-2): 251-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12376133&dopt=Abstract
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Simultaneous determination of the tobacco smoke uptake parameters nicotine, cotinine and thiocyanate in urine, saliva and hair, using gas chromatography-mass spectrometry for characterisation of smoking status of recently exposed subjects. Author(s): Torano JS, van Kan HJ. Source: The Analyst. 2003 July; 128(7): 838-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12894819&dopt=Abstract
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Slower metabolism and reduced intake of nicotine from cigarette smoking in Chinese-Americans. Author(s): Benowitz NL, Perez-Stable EJ, Herrera B, Jacob P 3rd. Source: Journal of the National Cancer Institute. 2002 January 16; 94(2): 108-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11792749&dopt=Abstract
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Smoke free hospitals: withdrawal from cigarettes should not be confused with withdrawal from nicotine. Author(s): McKee M, Gilmore A, Novotny T. Source: Bmj (Clinical Research Ed.). 2003 October 4; 327(7418): 811. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14525898&dopt=Abstract
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Smokeless tobacco: harm reduction or nicotine overload? Author(s): Vainio H, Weiderpass E. Source: European Journal of Cancer Prevention : the Official Journal of the European Cancer Prevention Organisation (Ecp). 2003 April; 12(2): 89-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12671531&dopt=Abstract
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Smokers deprived of cigarettes for 72 h: effect of nicotine patches on craving and withdrawal. Author(s): Teneggi V, Tiffany ST, Squassante L, Milleri S, Ziviani L, Bye A. Source: Psychopharmacology. 2002 November; 164(2): 177-87. Epub 2002 August 27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12404080&dopt=Abstract
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Smoking and ischemic stroke: a role for nicotine? Author(s): Hawkins BT, Brown RC, Davis TP. Source: Trends in Pharmacological Sciences. 2002 February; 23(2): 78-82. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11830264&dopt=Abstract
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Smoking and quitting with the aid of nicotine replacement therapies in the English adult population. Results from the Health Education Monitoring Survey 1995. Author(s): Buck D, Morgan A. Source: European Journal of Public Health. 2001 June; 11(2): 211-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11420814&dopt=Abstract
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Smoking cessation in the workplace: results of an intervention programme using nicotine patches. Author(s): Cruse SM, Forster NJ, Thurgood G, Sys L. Source: Occupational Medicine (Oxford, England). 2001 December; 51(8): 501-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11741082&dopt=Abstract
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Smoking cessation with nicotine replacement therapy among health care workers: randomized double-blind study. Author(s): Glavas D, Rumboldt M, Rumboldt Z. Source: Croatian Medical Journal. 2003 April; 44(2): 219-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12698515&dopt=Abstract
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Smoking cessation, smoking reduction, and delayed quitting among smokers given nicotine patches and a self-help pamphlet. Author(s): Jolicoeur DG, Richter KP, Ahluwalia JS, Mosier MC, Resnicow K. Source: Substance Abuse : Official Publication of the Association for Medical Education and Research in Substance Abuse. 2003 June; 24(2): 101-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12766377&dopt=Abstract
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Smoking cessation: nicotine replacement, gums and patches. Author(s): Tonnesen P. Source: Monaldi Arch Chest Dis. 1999 December; 54(6): 489-94. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10695317&dopt=Abstract
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Smoking for nicotine. Author(s): Johnson EW. Source: American Journal of Physical Medicine & Rehabilitation / Association of Academic Physiatrists. 2001 August; 80(8): 559. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11475473&dopt=Abstract
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Smoking history and nicotine effects on cognitive performance. Author(s): Ernst M, Heishman SJ, Spurgeon L, London ED. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2001 September; 25(3): 313-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11522460&dopt=Abstract
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Smoking, anxiety, and attention: support for the role of nicotine in attentionally mediated anxiolysis. Author(s): Kassel JD, Unrod M. Source: Journal of Abnormal Psychology. 2000 February; 109(1): 161-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10740949&dopt=Abstract
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Smoking, nicotine and tar and risk of small for gestational age babies. Author(s): Mitchell EA, Thompson JM, Robinson E, Wild CJ, Becroft DM, Clark PM, Glavish N, Pattison NS, Pryor JE. Source: Acta Paediatrica (Oslo, Norway : 1992). 2002; 91(3): 323-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12022307&dopt=Abstract
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Stopping smoking: the importance of nicotine addiction. Author(s): Hilton A. Source: Thorax. 2000 April; 55(4): 256-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10722761&dopt=Abstract
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Subjective and cardiovascular responses to nicotine combined with alcohol in male and female smokers. Author(s): Perkins KA, Sexton JE, DiMarco A, Grobe JE, Scierka A, Stiller RL. Source: Psychopharmacology. 1995 May; 119(2): 205-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7659768&dopt=Abstract
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Subjective effects of the nicotine lozenge: assessment of abuse liability. Author(s): Houtsmuller EJ, Henningfield JE, Stitzer ML. Source: Psychopharmacology. 2003 April; 167(1): 20-7. Epub 2003 March 04. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12616334&dopt=Abstract
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Subjective responses to nicotine in smokers may be associated with responses to caffeine and to alcohol. Author(s): Perkins KA, Fonte C, Ashcom J, Broge M, Wilson A. Source: Experimental and Clinical Psychopharmacology. 2001 February; 9(1): 91-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11519639&dopt=Abstract
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Successful treatment of orogenital ulceration with transdermal nicotine patches. Author(s): Kanekura T, Kanzaki T. Source: The British Journal of Dermatology. 1999 December; 141(6): 1140-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10722271&dopt=Abstract
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Symptoms of nicotine dependence and other predictors of student smoking at school: implications for school smoking policy. Author(s): Soteriades ES, DiFranza JR, Savageau JA, Nicolaou M. Source: The Journal of School Health. 2003 April; 73(4): 154-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12728614&dopt=Abstract
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Synaptic mechanisms underlie nicotine-induced excitability of brain reward areas. Author(s): Mansvelder HD, Keath JR, McGehee DS. Source: Neuron. 2002 March 14; 33(6): 905-19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11906697&dopt=Abstract
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Synaptic plasticity and nicotine addiction. Author(s): Dani JA, Ji D, Zhou FM. Source: Neuron. 2001 August 16; 31(3): 349-52. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11516393&dopt=Abstract
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Synergistic effects of nicotine on arecoline-induced cytotoxicity in human buccal mucosal fibroblasts. Author(s): Chang YC, Hu CC, Tseng TH, Tai KW, Lii CK, Chou MY. Source: Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 2001 September; 30(8): 458-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11545236&dopt=Abstract
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Systemic absorption and effects of nicotine from smokeless tobacco. Author(s): Benowitz NL. Source: Advances in Dental Research. 1997 September; 11(3): 336-41. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9524434&dopt=Abstract
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Systemic nicotine exposure in tobacco harvesters. Author(s): D'Alessandro A, Benowitz NL, Muzi G, Eisner MD, Filiberto S, Fantozzi P, Montanari L, Abbritti G. Source: Archives of Environmental Health. 2001 May-June; 56(3): 257-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11480503&dopt=Abstract
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Systemic nicotine stimulates human adipose tissue lipolysis through local cholinergic and catecholaminergic receptors. Author(s): Andersson K, Arner P. Source: International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity. 2001 August; 25(8): 1225-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11477508&dopt=Abstract
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The association between degree of nicotine dependence and other health behaviours. Findings from a German general population study. Author(s): Schumann A, Hapke U, Rumpf HJ, Meyer C, John U. Source: European Journal of Public Health. 2001 December; 11(4): 450-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11766489&dopt=Abstract
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The association between high nicotine dependence and severe mental illness may be consistent across countries. Author(s): de Leon J, Becona E, Gurpegui M, Gonzalez-Pinto A, Diaz FJ. Source: The Journal of Clinical Psychiatry. 2002 September; 63(9): 812-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12363123&dopt=Abstract
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The biology of nicotine dependence: from the 1988 Surgeon General's Report to the present and into the future. Author(s): Benowitz NL. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 1999; 1 Suppl 2: S159-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11768175&dopt=Abstract
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The clinical effectiveness and cost-effectiveness of bupropion and nicotine replacement therapy for smoking cessation: a systematic review and economic evaluation. Author(s): Woolacott NF, Jones L, Forbes CA, Mather LC, Sowden AJ, Song FJ, Raftery JP, Aveyard PN, Hyde CJ, Barton PM. Source: Health Technology Assessment (Winchester, England). 2002; 6(16): 1-245. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12269277&dopt=Abstract
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The compensating behavior of smokers: taxes, tar, and nicotine. Author(s): Evans WN, Farrelly MC. Source: The Rand Journal of Economics. 1998 Fall; 29(3): 578-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11794360&dopt=Abstract
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The demand for nicotine replacement therapies. Author(s): Tauras JA, Chaloupka FJ. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2003 April; 5(2): 237-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745497&dopt=Abstract
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The effects of extrinsic context on nicotine discrimination. Author(s): Duka T, Seiss E, Tasker R. Source: Behavioural Pharmacology. 2002 February; 13(1): 39-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11990718&dopt=Abstract
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The effects of fluoxetine combined with nicotine inhalers in smoking cessation--a randomized trial. Author(s): Blondal T, Gudmundsson LJ, Tomasson K, Jonsdottir D, Hilmarsdottir H, Kristjansson F, Nilsson F, Bjornsdottir US. Source: Addiction (Abingdon, England). 1999 July; 94(7): 1007-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10707439&dopt=Abstract
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The effects of nicotine on specific eye tracking measures in schizophrenia. Author(s): Sherr JD, Myers C, Avila MT, Elliott A, Blaxton TA, Thaker GK. Source: Biological Psychiatry. 2002 October 1; 52(7): 721-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12372663&dopt=Abstract
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The effects of transdermal nicotine on inspection time. Author(s): Thompson JC, Wilby G, Stough C. Source: Human Psychopharmacology. 2002 April; 17(3): 157-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12404693&dopt=Abstract
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The Fagerstrom Test for Nicotine Dependence and the Diagnostic Interview Schedule: do they diagnose the same smokers? Author(s): Moolchan ET, Radzius A, Epstein DH, Uhl G, Gorelick DA, Cadet JL, Henningfield JE. Source: Addictive Behaviors. 2002 January-February; 27(1): 101-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11800217&dopt=Abstract
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The hardest thing is the habit: a qualitative investigation of adolescent smokers' experience of nicotine dependence. Author(s): O'Loughlin J, Kishchuk N, DiFranza J, Tremblay M, Paradis G. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2002 May; 4(2): 201-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12028853&dopt=Abstract
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The heritability of failed smoking cessation and nicotine withdrawal in twins who smoked and attempted to quit. Author(s): Xian H, Scherrer JF, Madden PA, Lyons MJ, Tsuang M, True WR, Eisen SA. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2003 April; 5(2): 245-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745498&dopt=Abstract
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The influence of pH and nicotine concentration in oral moist snuff on mucosal changes and salivary pH in Swedish snuff users. Author(s): Andersson G, Warfvinge G. Source: Swed Dent J. 2003; 27(2): 67-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12856395&dopt=Abstract
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The need for dissemination of evidence-based results from research on nicotine and tobacco. Author(s): Swan GE. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2003 February; 5(1): 7-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745501&dopt=Abstract
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The origin of a nicotine detection method. Author(s): Ogden MW. Source: Aihaj : a Journal for the Science of Occupational and Environmental Health and Safety. 2001 November-December; 62(6): 665-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11767927&dopt=Abstract
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The potential role of cotinine in the cognitive and neuroprotective actions of nicotine. Author(s): Buccafusco JJ, Terry AV Jr. Source: Life Sciences. 2003 May 16; 72(26): 2931-42. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12706481&dopt=Abstract
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The role of cortisol suppression on craving for and satisfaction from nicotine in high and low impulsive subjects. Author(s): Reuter M, Netter P, Rogausch A, Sander P, Kaltschmidt M, Dorr A, Hennig J. Source: Human Psychopharmacology. 2002 July; 17(5): 213-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12404678&dopt=Abstract
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The role of nitric oxide in cigarette smoking and nicotine addiction. Author(s): Vleeming W, Rambali B, Opperhuizen A. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2002 August; 4(3): 341-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12215243&dopt=Abstract
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The Society for Research in Nicotine and Tobacco--an amazing success story. Author(s): West R. Source: Addiction (Abingdon, England). 2001 December; 96(12): 1867. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11791540&dopt=Abstract
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The subjective effects of nicotine: methodological issues, a review of experimental studies, and recommendations for future research. Author(s): Kalman D. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2002 February; 4(1): 25-70. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11906682&dopt=Abstract
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The use of nicotine in dermatology revisited. Author(s): Burkhart CG, Burkhart CN. Source: International Journal of Dermatology. 2001 November; 40(11): 731-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11737446&dopt=Abstract
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The vagus nerve, macrophages, and nicotine. Author(s): Floto RA, Smith KG. Source: Lancet. 2003 March 29; 361(9363): 1069-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12672307&dopt=Abstract
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The war against nicotine and tobacco: new tools? Author(s): Cerny T. Source: Onkologie. 2002 October; 25(5): 404. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12472104&dopt=Abstract
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Time course of appearance of cotinine in human beard hair after a single dose of nicotine. Author(s): Gwent SH, Wilson JF, Tsanaclis LM, Wicks JF. Source: Therapeutic Drug Monitoring. 1995 April; 17(2): 195-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7624910&dopt=Abstract
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Tobacco smoking and nicotine dependence: biological basis for pharmacotherapy from nicotine to treatments that prevent relapse. Author(s): Gold MS, Herkov MJ. Source: Journal of Addictive Diseases : the Official Journal of the Asam, American Society of Addiction Medicine. 1998; 17(1): 7-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9549599&dopt=Abstract
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Tobacco smoking, nicotine, and nicotine and non-nicotine replacement therapies. Author(s): Frishman WH, Ky T, Ismail A. Source: Heart Disease. 2001 November-December; 3(6): 365-77. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11975821&dopt=Abstract
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Tobacco use outcomes among patients with lung cancer treated for nicotine dependence. Author(s): Sanderson Cox L, Patten CA, Ebbert JO, Drews AA, Croghan GA, Clark MM, Wolter TD, Decker PA, Hurt RD. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 August 15; 20(16): 3461-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12177107&dopt=Abstract
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Tobacco, nicotine, and human cognition. Author(s): Heishman SJ, Henningfield JE, Singleton EG. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2002 February; 4(1): 3-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11906678&dopt=Abstract
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Toenail nicotine levels as a biomarker of tobacco smoke exposure. Author(s): Al-Delaimy WK, Mahoney GN, Speizer FE, Willett WC. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 2002 November; 11(11): 1400-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12433718&dopt=Abstract
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Transdermal nicotine as maintenance therapy for ulcerative colitis. Author(s): Thomas GA, Rhodes J, Mani V, Williams GT, Newcombe RG, Russell MA, Feyerabend C. Source: The New England Journal of Medicine. 1995 April 13; 332(15): 988-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7885427&dopt=Abstract
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Transdermal nicotine for agitation in dementia. Author(s): Rosin RA, Levine MD, Peskind E. Source: The American Journal of Geriatric Psychiatry : Official Journal of the American Association for Geriatric Psychiatry. 2001 Fall; 9(4): 443-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11739072&dopt=Abstract
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Transdermal nicotine in PD: a randomized, double-blind, placebo-controlled study. Author(s): Allam MF. Source: Neurology. 2002 April 9; 58(7): 1133; Author Reply 1133. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11940713&dopt=Abstract
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Transport mechanisms of nicotine across the human intestinal epithelial cell line Caco-2. Author(s): Fukada A, Saito H, Inui K. Source: The Journal of Pharmacology and Experimental Therapeutics. 2002 August; 302(2): 532-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12130712&dopt=Abstract
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Treating nicotine dependence during pregnancy and postpartum: understanding clinician knowledge and performance. Author(s): Bonollo DP, Zapka JG, Stoddard AM, Ma Y, Pbert L, Ockene JK. Source: Patient Education and Counseling. 2002 December; 48(3): 265-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12477611&dopt=Abstract
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Treatment of a habitual smoker using nicotine gum: a case report. Author(s): Wall JR. Source: Va Dent J. 1996 January-March; 73(1): 17-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9540751&dopt=Abstract
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Treatment of spit tobacco users with transdermal nicotine system and mint snuff. Author(s): Hatsukami DK, Grillo M, Boyle R, Allen S, Jensen J, Bliss R, Brown S. Source: Journal of Consulting and Clinical Psychology. 2000 April; 68(2): 241-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10780124&dopt=Abstract
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Treatment resistant smokers: a pilot study of nicotine nasal spray and inhaler. Author(s): Hughes JR, Grass JA, Pillitteri JL. Source: Journal of Addictive Diseases : the Official Journal of the Asam, American Society of Addiction Medicine. 2000; 19(1): 95-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10772606&dopt=Abstract
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Trends in sales weighted tar, nicotine, and carbon monoxide yields of UK cigarettes. Author(s): Jarvis MJ. Source: Thorax. 2001 December; 56(12): 960-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11713360&dopt=Abstract
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Ulcerative colitis responsive to smoking and to nicotine chewing gum in a patient with alpha 1 anti-trypsin deficiency. Author(s): Watson JP, Lewis RA. Source: Respiratory Medicine. 1995 October; 89(9): 635-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7494920&dopt=Abstract
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Up-regulation of epidermal growth factor-receptors (EGF-R) by nicotine in cervical cancer cell lines: this effect may be mediated by EGF. Author(s): Mathur RS, Mathur SP, Young RC. Source: American Journal of Reproductive Immunology (New York, N.Y. : 1989). 2000 August; 44(2): 114-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10994639&dopt=Abstract
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Uptake of nicotine in hair during controlled environmental air exposure to nicotine vapour: evidence for a major contribution of environmental nicotine to the overall nicotine found in hair from smokers and non-smokers. Author(s): Nilsen T, Zahlsen K, Nilsen OG. Source: Pharmacology & Toxicology. 1994 September-October; 75(3-4): 136-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7800653&dopt=Abstract
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Urinary nicotine metabolite excretion and lung cancer risk in a female cohort. Author(s): Ellard GA, de Waard F, Kemmeren JM. Source: British Journal of Cancer. 1995 September; 72(3): 788-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7669596&dopt=Abstract
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Urticarial reaction following the inhalation of nicotine in tobacco smoke. Author(s): Lee IW, Ahn SK, Choi EH, Lee SH. Source: The British Journal of Dermatology. 1998 March; 138(3): 486-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9580805&dopt=Abstract
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Usage patterns of transdermal nicotine when purchased as a non-prescription medicine from pharmacies. Author(s): Shaw JP, Ferry DG, Pethica D, Brenner D, Tucker IG. Source: Tobacco Control. 1998 Summer; 7(2): 161-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9789935&dopt=Abstract
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Use and effectiveness of transdermal nicotine in primary care settings. Author(s): White DR. Source: Archives of Family Medicine. 1995 April; 4(4): 304. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7711911&dopt=Abstract
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Use and effectiveness of transdermal nicotine in primary care settings. Author(s): Cummings KM, Biernbaum RM, Zevon MA, Deloughry T, Jaen CR. Source: Archives of Family Medicine. 1994 August; 3(8): 682-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7952254&dopt=Abstract
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Use of carbon-11 nicotine in PET studies. Author(s): Lundqvist H, Langstrom B, Nordberg A. Source: European Journal of Nuclear Medicine. 1997 July; 24(7): 825-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9289404&dopt=Abstract
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Use of nicotine replacement therapy in adolescent smokers and nonsmokers. Author(s): Klesges LM, Johnson KC, Somes G, Zbikowski S, Robinson L. Source: Archives of Pediatrics & Adolescent Medicine. 2003 June; 157(6): 517-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12796230&dopt=Abstract
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Use of over-the-counter nicotine patch for smoking cessation: prudent or premature? Author(s): McNagny SE, Ahluwalia JS. Source: Jama : the Journal of the American Medical Association. 1996 August 7; 276(5): 371-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8683812&dopt=Abstract
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Use of the fagerstrom tolerance questionnaire for measuring nicotine dependence among adolescent smokers in China: a pilot test. Author(s): Chen X, Zheng H, Steve S, Gong J, Stacy A, Xia J, Gallaher P, Dent C, Azen S, Shan J, Unger JB, Johnson CA. Source: Psychology of Addictive Behaviors : Journal of the Society of Psychologists in Addictive Behaviors. 2002 September; 16(3): 260-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12236462&dopt=Abstract
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Use of the nicotine patch by pregnant women. Author(s): Hackman R, Kapur B, Koren G. Source: The New England Journal of Medicine. 1999 November 25; 341(22): 1700. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10610440&dopt=Abstract
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Use of the nicotine skin patch by smokers in 20 communities in the United States, 1992-1993. Author(s): Cummings KM, Hyland A, Ockene JK, Hymowitz N, Manley M. Source: Tobacco Control. 1997; 6 Suppl 2: S63-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9583655&dopt=Abstract
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Use of transdermal nicotine systems in a possible suicide attempt. Author(s): Montalto N, Brackett CC, Sobol T. Source: The Journal of the American Board of Family Practice / American Board of Family Practice. 1994 September-October; 7(5): 417-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7810357&dopt=Abstract
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Using nicotine measurements and parental reports to assess indoor air: the PIAMA birth cohort study. Prevention and Incidence of Asthma and Mite Allergy. Author(s): Brunekreef B, Leaderer BP, van Strien R, Oldenwening M, Smit HA, Koopman L, Kerkhof M. Source: Epidemiology (Cambridge, Mass.). 2000 May; 11(3): 350-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10784258&dopt=Abstract
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Using nicotine replacement therapy in treating nicotine addiction in adolescents. Author(s): Maharaj K, Ternullo S. Source: J Sch Nurs. 2001 October; 17(5): 278-82. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11885345&dopt=Abstract
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Using qualitative research to inform survey development on nicotine dependence among adolescents. Author(s): Nichter M, Nichter M, Thompson PJ, Shiffman S, Moscicki AB. Source: Drug and Alcohol Dependence. 2002 November; 68 Suppl 1: S41-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12324174&dopt=Abstract
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Using the nicotine patch to stop smoking. Author(s): Richardson GS. Source: Jama : the Journal of the American Medical Association. 1995 January 18; 273(3): 181; Author Reply 182. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7880259&dopt=Abstract
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Using the nicotine patch to stop smoking. Author(s): Haxby D, Toffler WL. Source: Jama : the Journal of the American Medical Association. 1995 January 18; 273(3): 181-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7807644&dopt=Abstract
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Using the nicotine patch to stop smoking. Author(s): Swartz SH. Source: Jama : the Journal of the American Medical Association. 1995 January 18; 273(3): 181; Author Reply 182. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7807643&dopt=Abstract
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Utilization of nicotine nasal spray in smoking cessation. Author(s): Montalto NJ, Garrett SD. Source: J Am Osteopath Assoc. 1998 March; 98(3): 160-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9558832&dopt=Abstract
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Vaccines against nicotine: how effective are they likely to be in preventing smoking? Author(s): Vocci FJ, Chiang CN. Source: Cns Drugs. 2001; 15(7): 505-14. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11510621&dopt=Abstract
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Validation of self-reported smoking by analysis of hair for nicotine and cotinine. Author(s): Eliopoulos C, Klein J, Koren G. Source: Therapeutic Drug Monitoring. 1996 October; 18(5): 532-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8885115&dopt=Abstract
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Validity of the Fagerstrom test for nicotine dependence and of the Heaviness of Smoking Index among relatively light smokers. Author(s): Etter JF, Duc TV, Perneger TV. Source: Addiction (Abingdon, England). 1999 February; 94(2): 269-81. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10396794&dopt=Abstract
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Variable CYP2A6-mediated nicotine metabolism alters smoking behavior and risk. Author(s): Tyndale RF, Sellers EM. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2001 April; 29(4 Pt 2): 548-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11259349&dopt=Abstract
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Variation within global cigarette brands in tar, nicotine, and certain nitrosamines: analytic study. Author(s): Gray N, Zaridze D, Robertson C, Krivosheeva L, Sigacheva N, Boyle P. Source: Tobacco Control. 2000 September; 9(3): 351. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11203247&dopt=Abstract
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Varying nicotine patch dose and type of smoking cessation counseling. Author(s): Jorenby DE, Smith SS, Fiore MC, Hurt RD, Offord KP, Croghan IT, Hays JT, Lewis SF, Baker TB. Source: Jama : the Journal of the American Medical Association. 1995 November 1; 274(17): 1347-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7563558&dopt=Abstract
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Vasculitis attributed to the nicotine patch (Nicotinell). Author(s): Van der Klauw MM, Van Hillo B, Van den Berg WH, Bolsius EP, Sutorius FF, Stricker BH. Source: The British Journal of Dermatology. 1996 February; 134(2): 361-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8746358&dopt=Abstract
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Vertical nystagmus in normal subjects: effects of head position, nicotine and scopolamine. Author(s): Kim JI, Somers JT, Stahl JS, Bhidayasiri R, Leigh RJ. Source: Journal of Vestibular Research : Equilibrium & Orientation. 2000; 10(6): 291-300. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11455110&dopt=Abstract
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Vice President Al Gore. Plenary address at Addicted To Nicotine: A National Research Forum July 27-28, 1998, Bethesda, MD. Author(s): Gore A. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 1999; 1 Suppl 2: S13-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11768170&dopt=Abstract
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Weight change after smoking cessation using variable doses of transdermal nicotine replacement. Author(s): Dale LC, Schroeder DR, Wolter TD, Croghan IT, Hurt RD, Offord KP. Source: Journal of General Internal Medicine : Official Journal of the Society for Research and Education in Primary Care Internal Medicine. 1998 January; 13(1): 9-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9462489&dopt=Abstract
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Weight gain and insulin resistance during nicotine replacement therapy. Author(s): Assali AR, Beigel Y, Schreibman R, Shafer Z, Fainaru M. Source: Clin Cardiol. 1999 May; 22(5): 357-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10326169&dopt=Abstract
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What aspects of human performance are truly enhanced by nicotine? Author(s): Heishman SJ. Source: Addiction (Abingdon, England). 1998 March; 93(3): 317-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10328040&dopt=Abstract
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What is the most effective nicotine replacement therapy? Author(s): Diefenbacher LJ, Smith PO, Nashelsky J. Source: The Journal of Family Practice. 2003 June; 52(6): 492-4; Discussion 494. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12791233&dopt=Abstract
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What's new in Nicotine & Tobacco Research? Author(s): Hebert R. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2001 February; 3(1): 3-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11260805&dopt=Abstract
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What's new in Nicotine & Tobacco Research? Author(s): Hebert R. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2000 November; 2(4): 313-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11197309&dopt=Abstract
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What's new in Nicotine & Tobacco Research? Author(s): Hebert R. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2000 August; 2(3): 213-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11082820&dopt=Abstract
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Which smokers are helped to give up smoking using transdermal nicotine patches? Results from a randomized, double-blind, placebo-controlled trial. Author(s): Yudkin PL, Jones L, Lancaster T, Fowler GH. Source: The British Journal of General Practice : the Journal of the Royal College of General Practitioners. 1996 March; 46(404): 145-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8731618&dopt=Abstract
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Who gets what symptom? Effects of psychiatric cofactors and nicotine dependence on patterns of smoking withdrawal symptomatology. Author(s): Pomerleau CS, Marks JL, Pomerleau OF. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2000 August; 2(3): 275-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11082828&dopt=Abstract
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Why Britain needs a nicotine regulation authority. To bring consistency and regulation to tobacco and alternative nicotine products. Author(s): Britton J, McNeill A. Source: Bmj (Clinical Research Ed.). 2001 May 5; 322(7294): 1077-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11337423&dopt=Abstract
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Women's Initiative for Nonsmoking (WINS V): under-use of nicotine replacement therapy. Author(s): Mahrer-Imhof R, Froelicher ES, Li WW, Parker KM, Benowitz N. Source: Heart & Lung : the Journal of Critical Care. 2002 September-October; 31(5): 36873. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12487015&dopt=Abstract
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Worsening of motor performance in patients with Parkinson's disease following transdermal nicotine administration. Author(s): Ebersbach G, Stock M, Muller J, Wenning G, Wissel J, Poewe W. Source: Movement Disorders : Official Journal of the Movement Disorder Society. 1999 November; 14(6): 1011-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10584678&dopt=Abstract
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Would-be quitters get help winning against nicotine. Author(s): Schultz S. Source: U.S. News & World Report. 2000 May 29; 128(21): 58-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10947311&dopt=Abstract
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CHAPTER 2. NUTRITION AND NICOTINE Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and nicotine.
Finding Nutrition Studies on Nicotine The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail:
[email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “nicotine” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.
7
Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.
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The following is a typical result when searching for recently indexed consumer information on nicotine: •
Ask the doctor. I am trying to help my husband stop smoking. He tried to use the antidepressant Zyban, but it didn't work. He has also tried the nicotine patch, and that didn't work either. Is there any reason why he shouldn't try both together? Source: Lee, T H Harv-Heart-Lett. 1999 June; 9(10): 8 1051-5313
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Can nicotine help Parkinson's? Source: Anonymous Johns-Hopkins-Med-Lett-Health-After-50. 1999 June; 11(4): 8 10421882
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I've heard that the nicotine skin patch is a new treatment for ulcerative colitis. Is this true? Source: Anonymous Mayo-Clin-Health-Lett. 1998 February; 16(2): 8 0741-6245
The following information is typical of that found when using the “Full IBIDS Database” to search for “nicotine” (or a synonym): •
A facile synthesis of cis-1-methyl-1,2,3,3a,4,8b- hexahydropyrrolo[3,2-f]pyrindine, an annulated nicotine analog. Author(s): Laboratory of Modern Synthetic Organic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, China 200032.
[email protected] Source: Zhai, H Liu, P Luo, S Fang, F Zhao, M Org-Lett. 2002 December 12; 4(25): 4385-6 1523-7060
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A pilot controlled trial of transdermal nicotine in the treatment of attention deficit hyperactivity disorder. Author(s): Center for Infant and Child Development, Center for Aging and Brain Repair, Departments of Psychiatry, Neurosurgery, Neuroscience Program, University of South Florida, Tampa, Florida, USA.
[email protected] Source: Shytle, R D Silver, A A Wilkinson, B J Sanberg, P R World-J-Biol-Psychiatry. 2002 July; 3(3): 150-5 1562-2975
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Acute cardiac effects of nicotine in healthy young adults. Author(s): Department of Pediatrics, The University of Arizona, 1501 N. Campbell Avenue, PO Box 245073, Tucson, AZ 85724-5073, USA. Source: Jolma, C D Samson, R A Klewer, S E Donnerstein, R L Goldberg, S J Echocardiography. 2002 August; 19(6): 443-8 0742-2822
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Acute ventilatory and circulatory reactions evoked by nicotine: are they excitatory or depressant? Author(s): Laboratory of Neurobiology, Catholic University of Chile, PO Box 114-D, Santiago 1, Chile. Source: Fernandez, R Larrain, C Zapata, P Respir-Physiolo-Neurobiol. 2002 November 19; 133(3): 173-82 1569-9048
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Alcohol and nicotine reduce cell proliferation and enhance apoptosis in dentate gyrus. Author(s): Department of Physiology, College of Medicine, Kyung Hee University, 1 Hoigi-dong, Dongdaemoon-gu, Seoul 130-701. Source: Jang, M H Shin, M C Jung, S B Lee, T H Bahn, G H Kwon, Y K Kim, E H Kim, C J Neuroreport. 2002 August 27; 13(12): 1509-13 0959-4965
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Attenuation of nicotine-induced antinociception, rewarding effects, and dependence in mu-opioid receptor knock-out mice. Author(s): Laboratori de Neurofarmacologia, Facultat de Ciencies de la Salut i de la Vida, Universitat Pompeu Fabra, 08003 Barcelona, Spain. Source: Berrendero, F Kieffer, B L Maldonado, R J-Neurosci. 2002 December 15; 22(24): 10935-40 1529-2401
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Beneficial effects of Hippophae rhamnoides L. on nicotine induced oxidative stress in rat blood compared with vitamin E. Author(s): Department of Pharmacology, Faculty of Medicine, Ataturk University, Erzurum, Turkey. Source: Suleyman, H Gumustekin, K Taysi, S Keles, S Oztasan, N Aktas, O Altinkaynak, K Timur, H Akcay, F Akar, S Dane, S Gul, M Biol-Pharm-Bull. 2002 September; 25(9): 1133-6 0918-6158
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Bupropion inhibits nicotine-evoked [(3)H]overflow from rat striatal slices preloaded with [(3)H]dopamine and from rat hippocampal slices preloaded with [(3)H]norepinephrine. Author(s): College of Pharmacy, University of Kentucky, Lexington, KY 40536-0082, USA. Source: Miller, D K Sumithran, S P Dwoskin, L P J-Pharmacol-Exp-Ther. 2002 September; 302(3): 1113-22 0022-3565
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Cellular and synaptic mechanisms of nicotine addiction. Author(s): Vrije Universiteit Amsterdam, Faculty of Earth and Life Sciences, De Boelelaan 1085, 1081 HV, Amsterdam, The Netherlands. Source: Mansvelder, H D McGehee, D S J-Neurobiol. 2002 December; 53(4): 606-17 00223034
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Changes in conformation and subcellular distribution of alpha4beta2 nicotinic acetylcholine receptors revealed by chronic nicotine treatment and expression of subunit chimeras. Author(s): Department of Pharmacology, University College London, London, WC1E 6BT, United Kingdom. Source: Harkness, P C Millar, N S J-Neurosci. 2002 December 1; 22(23): 10172-81 15292401
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Chronic nicotine treatment changes the axonal distribution of 68 kDa neurofilaments in the rat ventral tegmental area. Author(s): Department of Morphological and Biomedical Sciences, Section of Anatomy and Histology, University of Verona, Medical Faculty, Strada Le Grazie 8, 37134, Verona, Italy.
[email protected] Source: Sbarbati, A Bunnemann, B Cristofori, P Terron, A Chiamulera, C Merigo, F Benati, D Bernardi, P Osculati, F Eur-J-Neurosci. 2002 September; 16(5): 877-82 0953816X
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Chronic nicotine treatment leads to sustained stimulation of tyrosine hydroxylase gene transcription rate in rat adrenal medulla. Author(s): Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, New York 14642, USA.
[email protected] Source: Sun, B Sterling, C R Tank, A W J-Pharmacol-Exp-Ther. 2003 February; 304(2): 575-88 0022-3565
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Chronic self-administration of nicotine in rats impairs T cell responsiveness. Author(s): Immunology Program, Lovelace Respiratory Research Institute, 2425 Ridgecrest Road SE, Albuquerque, NM 87108, USA.
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Source: Kalra, R Singh, S P Kracko, D Matta, S G Sharp, B M Sopori, M L J-PharmacolExp-Ther. 2002 September; 302(3): 935-9 0022-3565 •
Cognitive mechanisms of nicotine on visual attention. Author(s): Department of Psychiatry, Medical College of Wisconsin, Milwaukee, WI 53226, USA. Source: Lawrence, N S Ross, T J Stein, E A Neuron. 2002 October 24; 36(3): 539-48 08966273
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Drug trace discrimination with nicotine and morphine in rats. Author(s): Section of Behavioural Pharmacology, Institute of Psychiatry, King's College London, UK.
[email protected] Source: Stolerman, I P Childs, E Hahn, B Morley, A Behav-Pharmacol. 2002 February; 13(1): 49-58 0955-8810
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Effect of nicotine and nicotinic receptors on anxiety and depression. Author(s): Department of Psychiatry, Yale University School of Medicine, 34 Park Street, New Haven, CT 06508, USA. Source: Picciotto, M R Brunzell, D H Caldarone, B J Neuroreport. 2002 July 2; 13(9): 1097-106 0959-4965
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Effect of nicotine, cotinine and phenethyl isothiocyanate on 4-(methylnitrosamino)-1(3-pyridyl)-1-butanone (NNK) metabolism in the Syrian golden hamster. Author(s): Walther Straub Institute of Pharmacology and Toxicology, LudwigMaximilians University of Munich, Nussbaumstrasse 26, D-80336, Munich, Germany.
[email protected] Source: Richter, E Tricker, A R Toxicology. 2002 September 30; 179(1-2): 95-103 0300483X
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Effects of a low dose of transdermal nicotine on information processing. Author(s): Laboratoire d'Analyse de la Performance Motrice Humaine (LAPMH), Faculte des Sciences du Sport, Universite de Poitiers, 4 allee Jean Monnet, 86000 Poitiers, France.
[email protected] Source: Davranche, K Audiffren, M Nicotine-Tob-Res. 2002 August; 4(3): 275-85 14622203
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Effects of nicotine chewing gum on UPDRS score and P300 in early-onset parkinsonism. Author(s): The 3rd Department of Internal Medicine, Hiroshima University School of Medicine, Japan. Source: Mitsuoka, T Kaseda, Y Yamashita, H Kohriyama, T Kawakami, H Nakamura, S Yamamura, Y Hiroshima-J-Med-Sci. 2002 March; 51(1): 33-9 0018-2052
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Effects of nicotine deprivation and irritability on physical aggression in male smokers. Author(s): Department of Psychology, University of Georgia, Athens, Georgia 306023013, USA. Source: Parrott, D J Zeichner, A Psychol-Addict-Behavolume 2001 June; 15(2): 133-9 0893-164X
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Effects of nicotine on bone mass and strength in aged female rats. Author(s): Osteoporosis Research Center, Creighton University, 610 N, 30th Street, Omaha, NE 68131, USA.
[email protected] Source: Akhter, M P Iwaniec, U T Haynatzki, G R Fung, Y K Cullen, D M Recker, R R JOrthop-Res. 2003 January; 21(1): 14-9 0736-0266
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Enhanced Escherichia coli invasion of human brain microvascular endothelial cells is associated with alternations in cytoskeleton induced by nicotine. Author(s): Childrens Hospital Los Angeles, University of Southern California, Los Angeles, CA 90027, USA. Source: Chen, Y H Chen, S H Jong, A Zhou, Z Y Li, W Suzuki, K Huang, S H CellMicrobiol. 2002 August; 4(8): 503-14 1462-5814
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Focus groups with pregnant smokers: barriers to cessation, attitudes to nicotine patch use and perceptions of cessation counselling by care providers. Author(s): Women's and Babies' Division, Women's and Children's Hospital, North Adelaide, Australia. Source: Hotham, E D Atkinson, E R Gilbert, A L Drug-Alcohol-Revolume 2002 June; 21(2): 163-8 0959-5236
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Gender differences in tobacco smoking: higher relative exposure to smoke than nicotine in women. Author(s): Department of Pharmacology, Centre for Research in Women's Health, Sunnybrook, Canada. Source: Zeman, M V Hiraki, L Sellers, E M J-Womens-Health-Gend-Based-Med. 2002 March; 11(2): 147-53 1524-6094
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Genetic variation in CYP2A6-mediated nicotine metabolism alters smoking behavior. Author(s): Center for Addictions and Mental Health, Toronto, Canada.
[email protected] Source: Tyndale, R F Sellers, E M Ther-Drug-Monit. 2002 February; 24(1): 163-71 01634356
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Genetically dystrophic mdx/mdx mice exhibit decreased response to nicotine in passive avoidance. Author(s): Dipartimento di Genetica e Biologia Molecolare, Italy. Source: Coccurello, R Castellano, C Paggi, P Mele, A Oliverio, A Neuroreport. 2002 July 2; 13(9): 1219-22 0959-4965
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Influence of arterial vs. venous sampling site on nicotine tolerance model selection and parameter estimation. Author(s): Department of Biopharmaceutical Sciences, School of Pharmacy, University of California at San Francisco, USA. Source: Schaedeli, F Pitsiu, M Benowitz, N L Gourlay, S G Verotta, D J-PharmacokinetPharmacodyn. 2002 February; 29(1): 49-66 1567-567X
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Lasting effects of adolescent nicotine exposure on the electroencephalogram, event related potentials, and locomotor activity in the rat. Author(s): The Scripps Research Institute, Department of Neuropharmacology, CVN-14, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
[email protected] Source: Slawecki, C J Ehlers, C L Brain-Res-Dev-Brain-Res. 2002 September 20; 138(1): 15-25 0165-3806
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Lesions of the tegmental pedunculopontine nucleus block the rewarding effects and reveal the aversive effects of nicotine in the ventral tegmental area. Author(s): Neurobiology Research Group, Department of Anatomy and Cell Biology, University of Toronto, Toronto, Ontario, Canada M5S 1A8.
[email protected] Source: Laviolette, S R Alexson, T O van der Kooy, D J-Neurosci. 2002 October 1; 22(19): 8653-60 1529-2401
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Managing nicotine addiction. Author(s): Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota at Twin Cities, Minneapolis 55455, USA.
[email protected] Source: Kotlyar, M Hatsukami, D K J-Dent-Educ. 2002 September; 66(9): 1061-73 00220337
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Mechanisms of cytotoxicity of nicotine in human periodontal ligament fibroblast cultures in vitro. Author(s): Department of Periodontics, College of Oral Medicine, Chung Shan Medical University Hospital, 110, Sec. 1, Chien-Kuo N. Road., Taichung, Taiwan. Source: Chang, Y C Huang, F M Tai, K W Yang, L C Chou, M Y J-Periodontal-Res. 2002 August; 37(4): 279-85 0022-3484
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Mechanisms of nicotine mediated communication between NGF-differentiated PC12 and HEL cells. Author(s): Division of the Cell Physiology, Department of Physiology, BMC, Uppsala University, Husargatan 3, Sweden. Source: Krjukova, J Akerman, K E Neuroreport. 2002 July 2; 13(9): 1157-61 0959-4965
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Microarray technology and its application on nicotine research. Author(s): Department of Pharmacology, University of Tennessee College of Medicine, Memphis 38163, USA.
[email protected] Source: Li, M D Konu, O Kane, J K Becker, K G Mol-Neurobiol. 2002 June; 25(3): 265-85 0893-7648
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Molecular orbital calculations and nicotine metabolism: a rationale for experimentally observed metabolite ratios. Author(s): School of Biomedical and Life Sciences, University of Surrey, Guildford, UK.
[email protected] Source: Lewis, D F Gorrod, J W Drug-Metabol-Drug-Interact. 2002; 19(1): 29-39 07925077
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Multimodal assessment of the effect of chewing gum on nicotine withdrawal. Author(s): Departrnent of Psychology, Texas Tech University, Lubbock 49409-2051, USA. Source: Cohen, L M Britt, D M Collins, F L Al'Absi, M McChargue, D E AddictBehavolume 2001 Mar-April; 26(2): 289-95 0306-4603
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N-glucuronidation of nicotine and cotinine in human: formation of cotinine glucuronide in liver microsomes and lack of catalysis by 10 examined UDPglucuronosyltransferases. Author(s): Drug Metabolism and Drug Disposition Group, University of Saskatchewan, Saskatoon, Saskatchewan, Canada. Source: Ghosheh, O Hawes, E M Drug-Metab-Dispos. 2002 September; 30(9): 991-6 00909556
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Nicotine and bone density around titanium implants: a histometric study in rabbits. Author(s): Department of Prosthodontics and Periodontics, Division of Periodontics, School of Dentistry at Piracicaba, UNICAMP, Sao Paulo, Brazil.
[email protected] Source: Nociti, F H Jr Stefani, C M Sallum, E A Duarte, P M Sallum, A W Implant-Dent. 2002; 11(2): 176-82 1056-6163
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Nicotine and nicotinic receptors; relevance to Parkinson's disease. Author(s): The Parkinson's Institute, Sunnyvale, CA
[email protected]
94089,
USA.
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Source: Quik, M Kulak, J M Neurotoxicology. 2002 October; 23(4-5): 581-94 0161-813X •
Nicotine dependence, withdrawal symptoms, and adolescents' readiness to quit smoking. Author(s): The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
[email protected] Source: Prokhorov, A V Hudmon, K S de Moor, C A Kelder, S H Conroy, J L Ordway, N Nicotine-Tob-Res. 2001 May; 3(2): 151-5 1462-2203
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Nicotine treatment decreases food intake and body weight via a leptin-independent pathway in Psammomys obesus. Author(s): Metabolic Research Unit, School of Health Sciences, Deakin University, Waurn Ponds, Victoria, Australia.
[email protected] Source: Sanigorski, A Fahey, R Cameron Smith, D Collier, G R Diabetes-Obes-Metab. 2002 September; 4(5): 346-50 1462-8902
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Nicotine withdrawal syndrome: behavioural distress and selective up-regulation of the cyclic AMP pathway in the amygdala. Author(s): Eli Lilly and Company, Lilly Corporate Center, Neuroscience Discovery Research, Indianapolis, IN 46285-0510, USA. Source: Tzavara, E T Monory, K Hanoune, J Nomikos, G G Eur-J-Neurosci. 2002 July; 16(1): 149-53 0953-816X
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Nicotine-induced NO-mediated increase in cortical cerebral blood flow is blocked by beta2-adrenoceptor antagonists in the anesthetized rats. Author(s): Department of the Autonomic Nervous System, Tokyo Metropolitan Institute of Gerontology, Itabashi, Japan.
[email protected] Source: Uchida, S Kawashima, K Lee, T J Auton-Neurosci. 2002 March 18; 96(2): 126-30 1566-0702
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Nicotine-like discriminative stimulus effects of bupropion in rats. Author(s): Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond 23298-0613, USA.
[email protected] Source: Wiley, J L Lavecchia, K L Martin, B R Damaj, M I Exp-Clin-Psychopharmacol. 2002 May; 10(2): 129-35 1064-1297
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Nicotinic receptors mediate changes in spinal motoneuron development and axonal pathfinding in embryonic zebrafish exposed to nicotine. Author(s): Department of Biological Sciences, Louisiana State University, Baton Rouge, Louisiana 70803, USA. Source: Svoboda, K R Vijayaraghavan, S Tanguay, R L J-Neurosci. 2002 December 15; 22(24): 10731-41 1529-2401
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Nicotinic receptors mediate increased GABA release in brain through a tetrodotoxininsensitive mechanism during prolonged exposure to nicotine. Author(s): Department of Pharmacology, The George Washington University Medical Center, Washington, DC 20037, USA.
[email protected] Source: Zhu, P J Chiappinelli, V A Neuroscience. 2002; 115(1): 137-44 0306-4522
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Reboxetine: attenuation of intravenous nicotine self-administration in rats. Author(s): Department of Psychology, University of Kentucky, Lexington, KY 405360082, USA. Source: Rauhut, A S Mullins, S N Dwoskin, L P Bardo, M T J-Pharmacol-Exp-Ther. 2002 November; 303(2): 664-72 0022-3565
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Shed king cobra and cobra skins as model membranes for in-vitro nicotine permeation studies. Author(s): Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand.
[email protected] Source: Pongjanyakul, T Prakongpan, S Panomsuk, S Puttipipatkhachorn, S Priprem, A J-Pharm-Pharmacol. 2002 October; 54(10): 1345-50 0022-3573
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Smoking and quitting with the aid of nicotine replacement therapies in the English adult population. Results from the Health Education Monitoring Survey 1995. Author(s): Department of Dental Public Health & Oral Health Services Research, Guy's, King's and St. Thomas' (GKT) Medical and Dental Institute, King's College London, Guy's Tower, London Bridge, London SE1 9RT, UK.
[email protected] Source: Buck, D Morgan, A Eur-J-Public-Health. 2001 June; 11(2): 211-7 1101-1262
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SR141716, a central cannabinoid (CB(1)) receptor antagonist, blocks the motivational and dopamine-releasing effects of nicotine in rats. Author(s): Sanofi-Synthelabo, Bagneux, France.
[email protected] Source: Cohen, C Perrault, G Voltz, C Steinberg, R Soubrie, P Behav-Pharmacol. 2002 September; 13(5-6): 451-63 0955-8810
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The clinical effectiveness and cost-effectiveness of bupropion and nicotine replacement therapy for smoking cessation: a systematic review and economic evaluation. Author(s): NHS Center for Reviews and Dissemination, University of York, UK Source: Woolacott, N F Jones, L Forbes, C A Mather, L C Sowden, A J Song, F J Raftery, J P Aveyard, P N Hyde, C J Barton, P M Health-Technol-Assess. 2002; 6(16): 1-245 13665278
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The role of nitric oxide in cigarette smoking and nicotine addiction. Author(s): National Institute of Public Health and Environment, Laboratory of Health Effects Research, PO Box 1, NL 3720 BA Bilthoven, The Netherlands.
[email protected] Source: Vleeming, W Rambali, B Opperhuizen, A Nicotine-Tob-Res. 2002 August; 4(3): 341-8 1462-2203
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Upregulation of [3H]methyllycaconitine binding sites following continuous infusion of nicotine, without changes of alpha7 or alpha6 subunit mRNA: an autoradiography and in situ hybridization study in rat brain. Author(s): Biology Department, Psychiatry-CEDD, GlaxoSmithKline S.p.A., Medicines Research Centre, Verona, Italy.
[email protected] Source: Mugnaini, M Tessari, M Tarter, G Merlo Pich, E Chiamulera, C Bunnemann, B Eur-J-Neurosci. 2002 November; 16(9): 1633-46 0953-816X
Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •
healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0
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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov
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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov
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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/
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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/
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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/
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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/
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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/
Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html
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Google: http://directory.google.com/Top/Health/Nutrition/
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Healthnotes: http://www.healthnotes.com/
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Open Directory Project: http://dmoz.org/Health/Nutrition/
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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/
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WebMDHealth: http://my.webmd.com/nutrition
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
The following is a specific Web list relating to nicotine; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •
Vitamins Niacin Source: Integrative Medicine Communications; www.drkoop.com Niacin Alternative names: Vitamin B3 (Niacin) Source: Integrative Medicine Communications; www.drkoop.com Vitamin B3 (Niacin) Source: Integrative Medicine Communications; www.drkoop.com
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Vitamin B3 (Niacin) Alternative names: Niacin Source: Integrative Medicine Communications; www.drkoop.com •
Minerals Nicotine Alternatives Source: Healthnotes, Inc. www.healthnotes.com
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Food and Diet Hypertension Source: Healthnotes, Inc. www.healthnotes.com Oats Alternative names: Avena sativa Source: Healthnotes, Inc. www.healthnotes.com
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CHAPTER 3. ALTERNATIVE MEDICINE AND NICOTINE Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to nicotine. At the conclusion of this chapter, we will provide additional sources.
National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to nicotine and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “nicotine” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to nicotine: •
A comparative study of antioxidants S-allyl cysteine sulfoxide and vitamin E on the damages induced by nicotine in rats. Author(s): Helen A, Krishnakumar K, Vijayammal PL, Augusti KT. Source: Pharmacology. 2003 March; 67(3): 113-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12571405&dopt=Abstract
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A pharmacologic strategy for the treatment of nicotine addiction. Author(s): Dewey SL, Brodie JD, Gerasimov M, Horan B, Gardner EL, Ashby CR Jr. Source: Synapse (New York, N.Y.). 1999 January; 31(1): 76-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10025686&dopt=Abstract
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Acupuncture and nicotine withdrawal. Author(s): Paola F.
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Source: Archives of Internal Medicine. 1999 June 14; 159(11): 1256-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10371238&dopt=Abstract •
Acupuncture and nicotine withdrawal. Author(s): Low SA. Source: The Medical Journal of Australia. 1977 November 12; 2(20): 687. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=607120&dopt=Abstract
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Acute effect of nicotine on non-smokers: II. MLRs and 40-Hz responses. Author(s): Harkrider AW, Champlin CA. Source: Hearing Research. 2001 October; 160(1-2): 89-98. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11591494&dopt=Abstract
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Acute effect of nicotine on non-smokers: III. LLRs and EEGs. Author(s): Harkrider AW, Champlin CA. Source: Hearing Research. 2001 October; 160(1-2): 99-110. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11591495&dopt=Abstract
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Acute nicotine poisoning associated with a traditional remedy for eczema. Author(s): Davies P, Levy S, Pahari A, Martinez D. Source: Archives of Disease in Childhood. 2001 December; 85(6): 500-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11719343&dopt=Abstract
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Adverse effects of arecoline and nicotine on human periodontal ligament fibroblasts in vitro. Author(s): Chang YC, Lii CK, Tai KW, Chou MY. Source: Journal of Clinical Periodontology. 2001 March; 28(3): 277-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11284543&dopt=Abstract
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Alcohol, cannabis, nicotine, and caffeine use and symptom distress in schizophrenia. Author(s): Hamera E, Schneider JK, Deviney S. Source: The Journal of Nervous and Mental Disease. 1995 September; 183(9): 559-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7561817&dopt=Abstract
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An extractive-spectrophotometric method for the determination of nicotine. Author(s): Mahmoud, El-Sayed A, Mohamed YA. Source: Planta Medica. 1975 March; 27(2): 140-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1121527&dopt=Abstract
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Antioxidant role of oils isolated from garlic (Allium sativum Linn) and onion (Allium cepa Linn) on nicotine-induced lipid peroxidation. Author(s): Helen A, Rajasree CR, Krishnakumar K, Augusti KT, Vijayammal PL.
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Source: Vet Hum Toxicol. 1999 October; 41(5): 316-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10509436&dopt=Abstract •
Behavioral and EEG studies of acute cocaine administration: comparisons with morphine, amphetamine, pentobarbital, nicotine, ethanol and marijuana. Author(s): Lukas SE, Mendelson JH, Amass L, Benedikt R. Source: Nida Res Monogr. 1989; 95: 146-51. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2561820&dopt=Abstract
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Breastfeeding and the use of recreational drugs--alcohol, caffeine, nicotine and marijuana. Author(s): Liston J. Source: Breastfeed Rev. 1998 August; 6(2): 27-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9849117&dopt=Abstract
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Cannabis, nicotine and alcohol compared. Author(s): Heyndrickx A. Source: The New England Journal of Medicine. 1971 December 16; 285(25): 1437. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5121216&dopt=Abstract
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Cannabis: a Trojan horse for nicotine? Author(s): Burns CB, Ivers RG, Lindorff KJ, Clough AR. Source: Aust N Z J Public Health. 2000 December; 24(6): 637. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11215017&dopt=Abstract
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Changes in cholinergic activity and avoidance behavior by nicotine in differentially housed mice. Author(s): Essman WB. Source: The International Journal of Neuroscience. 1971 November; 2(4): 199-205. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5170637&dopt=Abstract
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Characterization of nicotinic acetylcholine receptors on cultured bovine adrenal chromaffin cells using modified L-[3H]nicotine binding assay. Author(s): Lee K, Miwa S, Koshimura K, Ito A. Source: Naunyn-Schmiedeberg's Archives of Pharmacology. 1992 April; 345(4): 363-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1620238&dopt=Abstract
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Chronic continuous infusion of nicotine increases the disappearance of choline acetyltransferase immunoreactivity in the cholinergic cell bodies of the medial septal nucleus following a partial unilateral transection of the fimbria fornix. Author(s): Fuxe K, Rosen L, Lippoldt A, Andbjer B, Hasselrot U, Finnman UB, Agnati LF.
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Source: Clin Investig. 1994 March; 72(4): 262-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8043972&dopt=Abstract •
Cigarette nicotine content as a determinant of human smoking behavior. Author(s): Goldfarb TL, Jarvik ME, Glick SD. Source: Psychopharmacologia. 1970; 17(1): 89-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5421216&dopt=Abstract
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Comparative effects of hypertension and nicotine on injury-induced myointimal thickening. Author(s): Krupski WC, Olive GC, Weber CA, Rapp JH. Source: Surgery. 1987 August; 102(2): 409-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3616923&dopt=Abstract
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Comparative studies of the adrenergic relaxations in the excised jejunum of rat, evoked by nicotine, tyramine, histamine, calcium and transmural stimulation; with a special reference to the catecholamine release. Author(s): Fujimoto K. Source: The Kobe Journal of Medical Sciences. 1969 June; 15(2): 71-105. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5346941&dopt=Abstract
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Covalently bound flavin in D-6-hydroxynicotine oxidase from Arthrobacter oxidans. Purification and properties of D-6-hydroxynicotine oxidase. Author(s): Bruhmuller M, Mohler H, Decker K. Source: European Journal of Biochemistry / Febs. 1972 August 18; 29(1): 143-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4628374&dopt=Abstract
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Dietary choline supplementation increases the density of nicotine binding sites in rat brain. Author(s): Coutcher JB, Cawley G, Wecker L. Source: The Journal of Pharmacology and Experimental Therapeutics. 1992 September; 262(3): 1128-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1326624&dopt=Abstract
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Does pharmacology corroborate the nicotine therapy and practices of South American shamanism? Author(s): Wilbert J. Source: Journal of Ethnopharmacology. 1991 April; 32(1-3): 179-86. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1881155&dopt=Abstract
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Effect of chronic nicotine delivery on the proliferation rate of endothelial and smooth muscle cells in experimentally induced vascular wall plaques. Author(s): Strohschneider T, Oberhoff M, Hanke H, Hannekum A, Karsch KR.
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Source: Clin Investig. 1994 November; 72(11): 908-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7894221&dopt=Abstract •
Effect of ginseng total saponin on extracellular dopamine release elicited by local infusion of nicotine into the striatum of freely moving rats. Author(s): Shim I, Javaid JI, Kim SE. Source: Planta Medica. 2000 December; 66(8): 705-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11199125&dopt=Abstract
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Effect of nicotine and cotinine on the susceptibility to in vitro oxidation of LDL in healthy non smokers and smokers. Author(s): Gouaze V, Dousset N, Dousset JC, Valdiguie P. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1998 September 14; 277(1): 25-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9776043&dopt=Abstract
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Effect of nicotine and other drugs on the release of 3H-norepinephrine and 3Hdopamine from rat brain slices. Author(s): Westfall TC. Source: Neuropharmacology. 1974 August; 13(8): 693-700. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4216859&dopt=Abstract
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Effect of nicotine on brain activation during performance of a working memory task. Author(s): Ernst M, Matochik JA, Heishman SJ, Van Horn JD, Jons PH, Henningfield JE, London ED. Source: Proceedings of the National Academy of Sciences of the United States of America. 2001 April 10; 98(8): 4728-33. Epub 2001 March 27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11274349&dopt=Abstract
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Effect of nicotine, lobeline, and mecamylamine on sensory gating in the rat. Author(s): Curzon P, Kim DJ, Decker MW. Source: Pharmacology, Biochemistry, and Behavior. 1994 December; 49(4): 877-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7886101&dopt=Abstract
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Effect of treatment for nicotine dependence on alcohol and drug treatment outcomes. Author(s): Joseph AM, Nichol KL, Anderson H. Source: Addictive Behaviors. 1993 November-December; 18(6): 635-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8178702&dopt=Abstract
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Effects of alpha 4/beta 2- and alpha 7-nicotine acetylcholine receptor agonists on prepulse inhibition of the acoustic startle response in rats and mice. Author(s): Schreiber R, Dalmus M, De Vry J.
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Source: Psychopharmacology. 2002 January; 159(3): 248-57. Epub 2001 October 19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11862357&dopt=Abstract •
Effects of chronic administration of nicotine on drug-induced hypnosis in mice. Author(s): Bhagat B, Bayer T, Lind C. Source: Psychopharmacologia. 1971; 21(3): 287-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5095417&dopt=Abstract
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Effects of colchicine and cytochalasin B on the release of 3 H-norepinephrine from guinea-pig atria evoked by high potassium, nicotine and tyramine. Author(s): Sorimachi M, Oesch F, Thoenen H. Source: Naunyn-Schmiedeberg's Archives of Pharmacology. 1973; 276(1): 1-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4347992&dopt=Abstract
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Effects of inhaled nicotine on instrumental learning of blood pressure responses. Author(s): Birbaumer N, Elbert T, Rockstroh B, Kramer J, Lutzenberger W, Grossmann P. Source: Biofeedback Self Regul. 1992 June; 17(2): 107-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1581396&dopt=Abstract
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Effects of neonatal exposure to nicotine on electrophysiological parameters in adult rats. Author(s): Ehlers CL, Somes C, Thomas J, Riley EP. Source: Pharmacology, Biochemistry, and Behavior. 1997 November; 58(3): 713-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9329064&dopt=Abstract
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Effects of nicotine deprivation on urges to drink and smoke in alcoholic smokers. Author(s): Cooney JL, Cooney NL, Pilkey DT, Kranzler HR, Oncken CA. Source: Addiction (Abingdon, England). 2003 July; 98(7): 913-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12814497&dopt=Abstract
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Effects of nicotine on body weight and food consumption in female rats. Author(s): Grunberg NE, Bowen DJ, Winders SE. Source: Psychopharmacology. 1986; 90(1): 101-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3094051&dopt=Abstract
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Effects of nicotine on EEG and evoked potentials and their interactions with autonomic drugs. Author(s): Guha D, Pradhan SN. Source: Neuropharmacology. 1976 April; 15(4): 225-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=934433&dopt=Abstract
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Effects of nicotine on hydroxyl free radical formation in vitro and on MPTP-induced neurotoxicity in vivo. Author(s): Ferger B, Spratt C, Earl CD, Teismann P, Oertel WH, Kuschinsky K. Source: Naunyn-Schmiedeberg's Archives of Pharmacology. 1998 September; 358(3): 351-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9774223&dopt=Abstract
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Effects of nicotine on spontaneous contractions of isolated atria of toad (Bufo melanostictus). Author(s): Koley J, Saha JK, Koley BN. Source: Arch Int Pharmacodyn Ther. 1987 July; 288(1): 71-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3116957&dopt=Abstract
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Effects of nicotine on the acoustic startle reflex amplitude in rats. Author(s): Acri JB, Grunberg NE, Morse DE. Source: Psychopharmacology. 1991; 104(2): 244-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1876669&dopt=Abstract
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Effects of nicotine on the human nasal mucosa. Author(s): Greiff L, Wollmer P, Erjefalt I, Andersson M, Pipkorn U, Persson CG. Source: Thorax. 1993 June; 48(6): 651-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8346498&dopt=Abstract
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Effects of nicotine on the immune response. I. Chronic exposure to nicotine impairs antigen receptor-mediated signal transduction in lymphocytes. Author(s): Geng Y, Savage SM, Johnson LJ, Seagrave J, Sopori ML. Source: Toxicology and Applied Pharmacology. 1995 December; 135(2): 268-78. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8545837&dopt=Abstract
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Electrophysiological responses to ethanol, pentobarbital, and nicotine in mice genetically selected for differential sensitivity to ethanol. Author(s): Ryan LJ, Barr JE, Sanders B, Sharpless SK. Source: J Comp Physiol Psychol. 1979 December; 93(6): 1035-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=521519&dopt=Abstract
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Ethanol- and nicotine-induced membrane changes in embryonic and neonatal chick brains. Author(s): Miller RR Jr, Heckel CD, Koss WJ, Montague SL, Greenman AL. Source: Comparative Biochemistry and Physiology. Toxicology & Pharmacology : Cbp. 2001 October; 130(2): 163-78. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11574286&dopt=Abstract
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Exposure to high ambient temperature increases absorption and plasma concentrations of transdermal nicotine. Author(s): Vanakoski J, Seppala T, Sievi E, Lunell E. Source: Clinical Pharmacology and Therapeutics. 1996 September; 60(3): 308-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8841153&dopt=Abstract
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Facilitation of learning and state dependency with nicotine. Author(s): Warburton DM, Wesnes K, Shergold K, James M. Source: Psychopharmacology. 1986; 89(1): 55-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3090592&dopt=Abstract
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Factors determining the success of nicotine withdrawal: 12-year follow-up of 532 smokers after suggestion therapy (by a faith healer). Author(s): Gmur M, Tschopp A. Source: Int J Addict. 1987 December; 22(12): 1189-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3436689&dopt=Abstract
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Free nicotine patches plus proactive telephone peer support to help low-income women stop smoking. Author(s): Solomon LJ, Scharoun GM, Flynn BS, Secker-Walker RH, Sepinwall D. Source: Preventive Medicine. 2000 July; 31(1): 68-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10896845&dopt=Abstract
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Gene expression in tobacco low-nicotine mutants. Author(s): Hibi N, Higashiguchi S, Hashimoto T, Yamada Y. Source: The Plant Cell. 1994 May; 6(5): 723-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8038607&dopt=Abstract
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Genetic influences on nicotine responses. Author(s): Marks MJ, Stitzel JA, Collins AC. Source: Pharmacology, Biochemistry, and Behavior. 1989 July; 33(3): 667-78. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2587608&dopt=Abstract
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Ginseng total saponin inhibits nicotine-induced hyperactivity and conditioned place preference in mice. Author(s): Kim HS, Kim KS, Oh KW. Source: Journal of Ethnopharmacology. 1999 July; 66(1): 83-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10432212&dopt=Abstract
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Helping people to stop smoking: randomised comparison of groups being treated with acupuncture and nicotine gum with control group. Author(s): Clavel F, Benhamou S, Company-Huertas A, Flamant R.
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Source: British Medical Journal (Clinical Research Ed.). 1985 November 30; 291(6508): 1538-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3933739&dopt=Abstract •
Hepatic and extrahepatic reduction of nicotine 1'-N-oxide in rats. Author(s): Dajani RM, Gorrod JW, Beckett AH. Source: The Biochemical Journal. 1972 November; 130(2): 88P. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4198087&dopt=Abstract
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Hypericum perforatum attenuates nicotine withdrawal signs in mice. Author(s): Catania MA, Firenzuoli F, Crupi A, Mannucci C, Caputi AP, Calapai G. Source: Psychopharmacology. 2003 September; 169(2): 186-9. Epub 2003 April 29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12719964&dopt=Abstract
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In vitro hepatic and extra-hepatic reduction of (minus)-nicotine-1'-N-oxide in rats. Author(s): Dajani RM, Gorrod JW, Beckett AH. Source: Biochemical Pharmacology. 1975 January 1; 24(1): 109-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=235926&dopt=Abstract
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In vivo influence of nicotine on human basal and NSAID-induced gut barrier function. Author(s): Suenaert P, Bulteel V, Den Hond E, Geypens B, Monsuur F, Luypaerts A, Ghoos Y, Rutgeerts P. Source: Scandinavian Journal of Gastroenterology. 2003 April; 38(4): 399-408. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12739712&dopt=Abstract
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Influence of tetrodotoxin and calcium on changes in extracellular dopamine levels evoked by systemic nicotine. Author(s): Benwell ME, Balfour DJ, Lucchi HM. Source: Psychopharmacology. 1993; 112(4): 467-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7871059&dopt=Abstract
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Inhibition of nicotine-DNA adduct formation in mice by six dietary constituents. Author(s): Cheng Y, Li HL, Wang HF, Sun HF, Liu YF, Peng SX, Liu KX, Guo ZY. Source: Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association. 2003 July; 41(7): 1045-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12804663&dopt=Abstract
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Inhibitory effect of Sejin-Eum I/II on nicotine- and cigarette extract-induced cytotoxicity in human lung fibroblast. Author(s): Jin JS, Kim MS, Yi JM, Lee JH, Lee JH, Moon SJ, Jung KP, Lee JK, An NH, Kim HM.
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Source: Journal of Ethnopharmacology. 2003 May; 86(1): 15-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12686436&dopt=Abstract •
Inhibitory effects of ginseng total saponin on nicotine-induced hyperactivity, reverse tolerance and dopamine receptor supersensitivity. Author(s): Kim HS, Kim KS. Source: Behavioural Brain Research. 1999 August; 103(1): 55-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10475164&dopt=Abstract
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Instructions control whether nicotine will serve as a reinforcer. Author(s): Hughes JR, Pickens RW, Spring W, Keenan RM. Source: The Journal of Pharmacology and Experimental Therapeutics. 1985 October; 235(1): 106-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4045717&dopt=Abstract
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IS MATERNAL COPPER SUPPLEMENTATION DURING ALVEOLARIZATION PROTECTING THE DEVELOPING RAT LUNG AGAINST THE ADVERSE EFFECTS OF MATERNAL NICOTINE EXPOSURE? A Morphometric Study. Author(s): Maritz GS, Windvogel S. Source: Experimental Lung Research. 2003 June; 29(4): 243-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12746049&dopt=Abstract
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Kicking the nicotine habit. How to help patients stop smoking. Author(s): Fletcher DJ. Source: Postgraduate Medicine. 1985 February 15; 77(3): 123-33. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3883327&dopt=Abstract
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Letter: Treatment of nicotine addiction with Avena sativa. Author(s): Gabrynowicz JW. Source: The Medical Journal of Australia. 1974 August 24; 2(8): 306-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4471694&dopt=Abstract
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Maternal copper supplementation protects the neonatal rat lung against the adverse effects of maternal nicotine exposure. Author(s): Maritz GS, Matthews HL, Aalbers J. Source: Reproduction, Fertility, and Development. 2000; 12(1-2): 97-103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11194564&dopt=Abstract
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Mecamylamine, but not atropine, antagonizes nicotine-induced hyperglycemia and potentiation of hypnosis produced by pentobarbital in mice. Author(s): Modak AT, Alderete BE.
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Source: Pharmacology. 1986; 32(1): 46-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3945673&dopt=Abstract •
Mechanism and specifcity of L- and D-6-hydroxynicotine oxidase. Author(s): Decker K, Dai VD. Source: European Journal of Biochemistry / Febs. 1967 December; 3(2): 132-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4965794&dopt=Abstract
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Mechanisms of mitogen-activated protein kinase activation by nicotine in small-cell lung carcinoma cells. Author(s): Cattaneo MG, D'atri F, Vicentini LM. Source: The Biochemical Journal. 1997 December 1; 328 ( Pt 2): 499-503. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9371707&dopt=Abstract
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Modulation of nicotine-evoked [3H]dopamine release from rat striatal synaptosomes by voltage-sensitive calcium channel ligands. Author(s): Prince RJ, Fernandes KG, Gregory JC, Martyn ID, Lippiello PM. Source: Biochemical Pharmacology. 1996 August 23; 52(4): 613-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8759034&dopt=Abstract
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Modulation of nicotine-induced analgesia by calcium agonist and antagonist in adult rats. Author(s): Chin CW, Block RC, Wu WH, Zbuzek VK. Source: Psychopharmacology. 1993; 110(4): 497-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7870921&dopt=Abstract
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Modulatory effect of ginseng total saponin on dopamine release and tyrosine hydroxylase gene expression induced by nicotine in the rat. Author(s): Shim IS, Won JS, Lee JK, Song DK, Kim SE, Huh SO, Kim YH, Suh HW. Source: Journal of Ethnopharmacology. 2000 May; 70(2): 161-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10771206&dopt=Abstract
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Nicotine addiction: treatment with medical hypnosis. Part 1. Author(s): Grosz HJ. Source: J Indiana State Med Assoc. 1978 November; 71(11): 1074-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=712101&dopt=Abstract
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Nicotine addiction: treatment with medical hypnosis. Part 2. Author(s): Grosz HJ.
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Source: J Indiana State Med Assoc. 1978 December; 71(12): 1136-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=722107&dopt=Abstract •
Nicotine addiction: treatment with medical hypnosis. Part 3. Author(s): Grosz HJ. Source: J Indiana State Med Assoc. 1979 January; 72(1): 43-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=758353&dopt=Abstract
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Nicotine blocks latent inhibition in rats: evidence for a critical role of increased functional activity of dopamine in the mesolimbic system at conditioning rather than pre-exposure. Author(s): Joseph MH, Peters SL, Gray JA. Source: Psychopharmacology. 1993; 110(1-2): 187-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7870882&dopt=Abstract
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Nicotine dependence and secondary effects of smoking cessation. Author(s): Clavel F, Benhamou S, Flamant R. Source: Journal of Behavioral Medicine. 1987 December; 10(6): 555-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3437446&dopt=Abstract
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Nicotine effects on biofeedback training. Author(s): Grimsley DL. Source: Journal of Behavioral Medicine. 1990 June; 13(3): 321-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2213873&dopt=Abstract
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Nicotine for the treatment of Tourette's syndrome. Author(s): Sanberg PR, Silver AA, Shytle RD, Philipp MK, Cahill DW, Fogelson HM, McConville BJ. Source: Pharmacology & Therapeutics. 1997; 74(1): 21-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9336013&dopt=Abstract
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Nicotine increases sensory gating measured as inhibition of the acoustic startle reflex in rats. Author(s): Acri JB, Morse DE, Popke EJ, Grunberg NE. Source: Psychopharmacology. 1994 March; 114(2): 369-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7838931&dopt=Abstract
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Nicotine induced inhibition of the activities of accessory reproductive ducts in male rats. Author(s): Londonkar RL, Srinivasreddy P, Somanathreddy P, Patil SB.
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Source: Journal of Ethnopharmacology. 1998 April; 60(3): 215-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9613835&dopt=Abstract •
Nicotine modulates effects of stress on acoustic startle reflexes in rats: dependence on dose, stressor and initial reactivity. Author(s): Acri JB. Source: Psychopharmacology. 1994 November; 116(3): 255-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7892414&dopt=Abstract
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Nicotine patch therapy in smoking cessation reduces the extent of exercise-induced myocardial ischemia. Author(s): Mahmarian JJ, Moye LA, Nasser GA, Nagueh SF, Bloom MF, Benowitz NL, Verani MS, Byrd WG, Pratt CM. Source: Journal of the American College of Cardiology. 1997 July; 30(1): 125-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9207632&dopt=Abstract
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Nicotine preference increases after cigarette deprivation. Author(s): Rose JE, Jarvik ME, Ananda S. Source: Pharmacology, Biochemistry, and Behavior. 1984 January; 20(1): 55-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6695000&dopt=Abstract
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Nicotine withdrawal leads to increased firing rates of midbrain dopamine neurons. Author(s): Rasmussen K, Czachura JF. Source: Neuroreport. 1995 December 29; 7(1): 329-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8742482&dopt=Abstract
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Nicotine withdrawal: a behavioral assessment using schedule controlled responding, locomotor activity, and sensorimotor reactivity. Author(s): Helton DR, Modlin DL, Tizzano JP, Rasmussen K. Source: Psychopharmacology. 1993; 113(2): 205-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7855182&dopt=Abstract
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Nicotine-induced analgesia in rats: the role of calcium and the diversity of responders and nonresponders. Author(s): Block RC, Chin CW, Wu W, Zbuzek VK. Source: Life Sciences. 1993; 53(12): Pl195-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8361323&dopt=Abstract
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Nicotine-induced inhibition of lycopene cyclization in Phaseolus vulgaris cotyledons. Author(s): Sadowski RA.
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Source: Biochemical and Biophysical Research Communications. 1984 April 30; 120(2): 625-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6732775&dopt=Abstract •
Normalizing effects of nicotine and a novel nicotinic agonist on hippocampal auditory gating in two animal models. Author(s): Stevens KE, Wear KD. Source: Pharmacology, Biochemistry, and Behavior. 1997 August; 57(4): 869-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9259018&dopt=Abstract
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Pharmacotherapy of nicotine dependence. Author(s): Haustein KO. Source: Int J Clin Pharmacol Ther. 2000 June; 38(6): 273-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10890576&dopt=Abstract
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Positive inotropic effect of nicotine on electrically evoked contraction of isolated toad ventricle. Author(s): Koley J, Saha JK, Koley BN. Source: Arch Int Pharmacodyn Ther. 1984 February; 267(2): 269-78. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6712360&dopt=Abstract
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Prenatal exposure to nicotine: effects on prepulse inhibition and central nicotinic receptors. Author(s): Popke EJ, Tizabi Y, Rahman MA, Nespor SM, Grunberg NE. Source: Pharmacology, Biochemistry, and Behavior. 1997 December; 58(4): 843-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9408185&dopt=Abstract
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Prenatal nicotine and CNS development. Author(s): Al-Hachim GM, Mahmoud FA. Source: Epilepsia. 1985 November-December; 26(6): 661-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4076070&dopt=Abstract
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Prevention of chronic alcohol and nicotine-induced azospermia, sterility and decreased libido, by a novel tri-substituted benzoflavone moiety from Passiflora incarnata Linneaus in healthy male rats. Author(s): Dhawan K, Sharma A. Source: Life Sciences. 2002 November 15; 71(26): 3059-69. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12408873&dopt=Abstract
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Psychophysiological effects of nicotine abstinence and behavioral challenges in habitual smokers. Author(s): al'Absi M, Amunrud T, Wittmers LE.
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Source: Pharmacology, Biochemistry, and Behavior. 2002 June; 72(3): 707-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12175468&dopt=Abstract •
Psychophysiological variables in cigarette smoking and reinforcing effects of nicotine. Author(s): Stephens RM. Source: Addictive Behaviors. 1977; 2(1): 1-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=322450&dopt=Abstract
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Randomized trial of acupuncture for nicotine withdrawal symptoms. Author(s): White AR, Resch KL, Ernst E. Source: Archives of Internal Medicine. 1998 November 9; 158(20): 2251-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9818805&dopt=Abstract
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Rapid loss of nicotine-cholinergic receptor binding activity in the deafferented avian optic lobe. Author(s): Brecha N, Francis A, Schechter N. Source: Brain Research. 1979 May 11; 167(2): 273-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=445129&dopt=Abstract
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Reinforcing effects of nicotine in humans and experimental animals responding under intermittent schedules of i.v. drug injection. Author(s): Goldberg SR, Henningfield JE. Source: Pharmacology, Biochemistry, and Behavior. 1988 May; 30(1): 227-34. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3051048&dopt=Abstract
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Self-reported alcohol and nicotine use and the ability to control occipital EEG in a biofeedback situation. Author(s): DeGood DE, Valle RS. Source: Addictive Behaviors. 1978; 3(1): 13-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=654992&dopt=Abstract
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Smoking cessation rates 4 years after treatment by nicotine gum and acupuncture. Author(s): Clavel-Chapelon F, Paoletti C, Benhamou S. Source: Preventive Medicine. 1997 January-February; 26(1): 25-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9010894&dopt=Abstract
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Smoking withdrawal, nicotine dependence and prepulse inhibition of the acoustic startle reflex. Author(s): Kumari V, Gray JA.
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Source: Psychopharmacology. 1999 January; 141(1): 11-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9952059&dopt=Abstract •
Stimulation of release of pinolysosomal contents of macrophages by nicotine. Author(s): Schwartz SL, Bond JC. Source: The Journal of Pharmacology and Experimental Therapeutics. 1972 November; 183(2): 378-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4628415&dopt=Abstract
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Synergistic effects of nicotine on arecoline-induced cytotoxicity in human buccal mucosal fibroblasts. Author(s): Chang YC, Hu CC, Tseng TH, Tai KW, Lii CK, Chou MY. Source: Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 2001 September; 30(8): 458-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11545236&dopt=Abstract
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Telephone support as an adjunct to transdermal nicotine in smoking cessation. Author(s): Lando HA, Rolnick S, Klevan D, Roski J, Cherney L, Lauger G. Source: American Journal of Public Health. 1997 October; 87(10): 1670-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9357351&dopt=Abstract
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The effect of ascorbic acid supplementation on the nicotine metabolism of smokers. Author(s): Dawson EB, Evans DR, Harris WA, McGanity WJ. Source: Preventive Medicine. 1999 December; 29(6 Pt 1): 451-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10600424&dopt=Abstract
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The effects of serotonin biosynthesis inhibition on nicotine and nifedipine-induced analgesia in rats. Author(s): Hunt TE, Wu WH, Zbuzek VK. Source: Anesthesia and Analgesia. 1998 November; 87(5): 1109-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9806690&dopt=Abstract
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The effects of smoking and cigarette nicotine content on smokers' preparation and performance of a psychosocially stressful task. Author(s): Hatch JP, Bierner SM, Fisher JG. Source: Journal of Behavioral Medicine. 1983 June; 6(2): 207-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6620373&dopt=Abstract
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The influence of nicotine on performance, mood, and physiological parameters as related to smoking habit, gender, and suggestibility. Author(s): Netter P, Muller MJ, Neumann A, Kamradik B.
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Source: Clin Investig. 1994 July; 72(7): 512-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7981579&dopt=Abstract •
The nicotine patch in smoking cessation. A randomized trial with telephone counseling. Author(s): Westman EC, Levin ED, Rose JE. Source: Archives of Internal Medicine. 1993 August 23; 153(16): 1917-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8250653&dopt=Abstract
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The novel 5-Hydroxytryptamine(1A) antagonist LY426965: effects on nicotine withdrawal and interactions with fluoxetine. Author(s): Rasmussen K, Calligaro DO, Czachura JF, Dreshfield-Ahmad LJ, Evans DC, Hemrick-Luecke SK, Kallman MJ, Kendrick WT, Leander JD, Nelson DL, Overshiner CD, Wainscott DB, Wolff MC, Wong DT, Branchek TA, Zgombick JM, Xu YC. Source: The Journal of Pharmacology and Experimental Therapeutics. 2000 August; 294(2): 688-700. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10900249&dopt=Abstract
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The purification and properties of nicotine oxidase. Author(s): Hochstein LI, Dalton BP. Source: Biochimica Et Biophysica Acta. 1967 May 16; 139(1): 56-68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4962139&dopt=Abstract
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The reinforcing properties of nicotine are associated with a specific patterning of cfos expression in the rat brain. Author(s): Pagliusi SR, Tessari M, DeVevey S, Chiamulera C, Pich EM. Source: The European Journal of Neuroscience. 1996 November; 8(11): 2247-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8950089&dopt=Abstract
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The vagus nerve, macrophages, and nicotine. Author(s): Floto RA, Smith KG. Source: Lancet. 2003 March 29; 361(9363): 1069-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12672307&dopt=Abstract
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Treatment of nicotine dependence. Author(s): Haxby DG. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 1995 February 1; 52(3): 265-81; Quiz 314-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7749954&dopt=Abstract
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Use of transdermal nicotine in a state-level prescription plan for the elderly. A first look at 'real-world' patch users. Author(s): Orleans CT, Resch N, Noll E, Keintz MK, Rimer BK, Brown TV, Snedden TM. Source: Jama : the Journal of the American Medical Association. 1994 February 23; 271(8): 601-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8301792&dopt=Abstract
Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •
Alternative Medicine Foundation, Inc.: http://www.herbmed.org/
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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats
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Chinese Medicine: http://www.newcenturynutrition.com/
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drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html
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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm
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Google: http://directory.google.com/Top/Health/Alternative/
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Healthnotes: http://www.healthnotes.com/
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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine
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Open Directory Project: http://dmoz.org/Health/Alternative/
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HealthGate: http://www.tnp.com/
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WebMDHealth: http://my.webmd.com/drugs_and_herbs
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/
The following is a specific Web list relating to nicotine; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •
General Overview Alzheimer's Disease Source: Integrative Medicine Communications; www.drkoop.com Angina Source: Healthnotes, Inc. www.healthnotes.com Atherosclerosis Source: Healthnotes, Inc. www.healthnotes.com
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Atherosclerosis and Heart Disease Prevention Source: Prima Communications, Inc.www.personalhealthzone.com Attention Deficit Hyperactivity Disorder Source: Integrative Medicine Communications; www.drkoop.com Bronchitis Source: Healthnotes, Inc. www.healthnotes.com Female Infertility Source: Healthnotes, Inc. www.healthnotes.com Heart Attack Source: Healthnotes, Inc. www.healthnotes.com High Blood Pressure Source: Integrative Medicine Communications; www.drkoop.com High Cholesterol Source: Healthnotes, Inc. www.healthnotes.com High Homocysteine Source: Healthnotes, Inc. www.healthnotes.com High Triglycerides Source: Healthnotes, Inc. www.healthnotes.com Hypertension Source: Integrative Medicine Communications; www.drkoop.com Insomnia Source: Healthnotes, Inc. www.healthnotes.com Insomnia Source: Integrative Medicine Communications; www.drkoop.com Insulin Resistance Syndrome Source: Healthnotes, Inc. www.healthnotes.com Intermittent Claudication Source: Healthnotes, Inc. www.healthnotes.com Leukemia Source: Integrative Medicine Communications; www.drkoop.com Lung Cancer Source: Integrative Medicine Communications; www.drkoop.com Ménière's Disease Source: Healthnotes, Inc. www.healthnotes.com
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Macular Degeneration Source: Healthnotes, Inc. www.healthnotes.com Multiple Sclerosis Source: Healthnotes, Inc. www.healthnotes.com Pancreatic Insufficiency Source: Healthnotes, Inc. www.healthnotes.com Peripheral Vascular Disease Source: Healthnotes, Inc. www.healthnotes.com Pregnancy and Postpartum Support Source: Healthnotes, Inc. www.healthnotes.com Raynaud's Disease Source: Healthnotes, Inc. www.healthnotes.com Raynaud's Phenomenon Source: Integrative Medicine Communications; www.drkoop.com Sleeplessness Source: Integrative Medicine Communications; www.drkoop.com Ulcerative Colitis Source: Healthnotes, Inc. www.healthnotes.com •
Herbs and Supplements Aesculus Alternative names: Horse Chestnut; Aesculus hippocastanum L. Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Aloe Alternative names: Aloe vera L. Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Equisetum Alternative names: Horsetail; Equisetum arvense L. Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Ginkgo Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Horsetail Source: Prima Communications, Inc.www.personalhealthzone.com Horsetail Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10105,00.html
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Indian Tobacco Source: Integrative Medicine Communications; www.drkoop.com Lobelia Alternative names: Lobelia inflata L. Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Lobelia Alternative names: Lobelia inflata Source: Healthnotes, Inc. www.healthnotes.com Lobelia Alternative names: Lobelia inflata, Indian Tobacco Source: Integrative Medicine Communications; www.drkoop.com Lobelia inflata Source: Integrative Medicine Communications; www.drkoop.com Panax Alternative names: Ginseng; Panax ginseng Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Piper nigrum Alternative names: Black Pepper Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Plantago major Alternative names: Plantain; Plantago major/lanceolata Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Taraxacum Alternative names: Dandelion; Taraxacum officinale (Dhudhal) Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Tyrosine Source: Integrative Medicine Communications; www.drkoop.com Uncaria asian Alternative names: Asian species; Uncaria sp. Source: Alternative Medicine Foundation, Inc. www.amfoundation.org
General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.
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CHAPTER 4. DISSERTATIONS ON NICOTINE Overview In this chapter, we will give you a bibliography on recent dissertations relating to nicotine. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “nicotine” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on nicotine, we have not necessarily excluded non-medical dissertations in this bibliography.
Dissertations on Nicotine ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to nicotine. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •
A Biobehavioural Approach to Understanding the Patterns of and Trajectory to Nicotine Dependence in Adolescents: an Examination of the Influences of Gender and Conditioning Factors by Faber, Dana Rochelle; Msc from University of Toronto (canada), 2002, 125 pages http://wwwlib.umi.com/dissertations/fullcit/MQ74146
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A Clinical Study of the Pharmacology of an Inhaled Nicotine Aerosol by Lux, Jo Ann Elizabeth; Phd from University of Toronto (canada), 1988 http://wwwlib.umi.com/dissertations/fullcit/NL43481
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A Pilot Study to Assess the Effects of a Single Intranasal Dose of Nicotine in Neuroendocrine, Cognitive and Behavioral Function in Healthy Young Smokers and Nonsmokers by Leu, Jocelyn Hsyn-yi; Phd from Virginia Commonwealth University, 2002, 480 pages http://wwwlib.umi.com/dissertations/fullcit/3066360
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A Placebo-controlled Randomized Trial of the Effects of Ppa and Nicotine Gum on Cessation Rates and Post-cessation Weight Gain in Women by Cooper, Theodore V. Phd from The University of Memphis, 2002, 39 pages http://wwwlib.umi.com/dissertations/fullcit/3054558
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A Study of Brain Acetylcholine Levels and Their Relationship to the Tremorogenic Effect of Nicotine-n-oxide in Mice by Madill, Herbert Dinsmore; Advdeg from The University of Western Ontario (canada), 1970 http://wwwlib.umi.com/dissertations/fullcit/NK06976
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Activation of Phospholipases A(2) and D of a Human Neuroblastoma Cell Line (la-n2) by N-dodecyl-l-lysine Amide (compound 24), a Putative G Protein Activator: Characteristics of Inhibition by (-)-nicotine by Garnham, Byron Mitchell; Msc from The University of Manitoba (canada), 2002, 120 pages http://wwwlib.umi.com/dissertations/fullcit/MQ76945
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Adolescent Nicotine Administration: Effects on Cns Serotonergic Systems by Xu, Zengjun; Phd from University of Arkansas for Medical Sciences, 2002, 118 pages http://wwwlib.umi.com/dissertations/fullcit/3070579
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Behavioral and Physiological Effects of Low Nicotine Cigarettes during Rapid Smoking by Russell, Peggy O'hara, Phd from University of Pittsburgh, 1981, 97 pages http://wwwlib.umi.com/dissertations/fullcit/8208686
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Biopsychosocial Treatment of Nicotine Dependency: Partner Participation Versus No Partner Group Treatment by Martinez, Rey Caytano, Phd from The Florida State University, 1994, 133 pages http://wwwlib.umi.com/dissertations/fullcit/9529606
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Cognitive Assessment in Computerized Nicotine Fading (smoking Cessation) by Gonzalez, Roberto Cortez, Phd from Stanford University, 1990, 317 pages http://wwwlib.umi.com/dissertations/fullcit/9102269
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Depression and Smoking Relapse: an Evaluation of Nicotine Mechanisms by Balabanis, Mark Homer; Phd from University of Pittsburgh, 2002, 113 pages http://wwwlib.umi.com/dissertations/fullcit/3066932
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Effect of Counselor and Client Education in Nicotine Addiction on Substance Abusers' Readiness to Begin Smoking Cessation Treatment by Perine, Jessica Lee, Phd from Hofstra University, 1997, 123 pages http://wwwlib.umi.com/dissertations/fullcit/9804829
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Effect of Nicotine on Healing of the Rat Mandibular Distraction Wound by Schulten, Alcuin Justus Maxime; Dmsc from Harvard University, 2002 http://wwwlib.umi.com/dissertations/fullcit/f662097
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Effects of Nicotine on Osteogenesis by Sanoudos, Mattheos; Phd from Indiana University, 2002, 213 pages http://wwwlib.umi.com/dissertations/fullcit/3054390
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Effects of Nicotine Vaccination on Blood Pressure and Grip Strength by Rice, Shelia Renee; Ma from University of Houston-clear Lake, 2002, 93 pages http://wwwlib.umi.com/dissertations/fullcit/1413710
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Evaluation of the Ending Nicotine Dependence Program by Librett, John James; Phd from The University of Utah, 2001, 166 pages http://wwwlib.umi.com/dissertations/fullcit/3027432
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Identifying Predictor Variables for Nicotine Addiction among Individuals Who Experiment with Cigarette Smoking in Adolescence by Sanchez, Peter Joel; Phd from New Mexico State University, 2002, 186 pages http://wwwlib.umi.com/dissertations/fullcit/3051880
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Impact of Nicotine Exposure on Brain Development Assessed by Proton Magnetic Resonance Spectroscopy by Cloak, Christine Carol; Phd from University of California, Los Angeles, 2002, 122 pages http://wwwlib.umi.com/dissertations/fullcit/3040206
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Long-term Oral Nicotine Treatment and Daily Variations in Brain Monoamines and Motor Activity by Gaddnas, Helena Maria; Phd from Helsingin Yliopisto (finland), 2002, 89 pages http://wwwlib.umi.com/dissertations/fullcit/f684017
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Nicotine Withdrawal and Gender: a Placebo Control Study by Buchhalter, August Robert; Phd from Virginia Commonwealth University, 2002, 156 pages http://wwwlib.umi.com/dissertations/fullcit/3058267
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Nicotine-induced Effects on the Bone Vasculature by Feitelson, Jeremy Bejamine Andrews; Phd from University of Louisville, 2002, 81 pages http://wwwlib.umi.com/dissertations/fullcit/3054161
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Nicotine's Effect upon the Eye Movements Associated with Reading and Reading Comprehension by Barnes, Laura E. Phd from University of Missouri - Saint Louis, 2003, 62 pages http://wwwlib.umi.com/dissertations/fullcit/3081313
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Pharmacologic Effects and Safety of Tranylcypromine Inhibition of Nicotine Metabolism in Humans by Fernandes, Leona Caterina; Msc from University of Toronto (canada), 2002, 194 pages http://wwwlib.umi.com/dissertations/fullcit/MQ74129
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Short-term Distribution of Nicotine in the Rat by Brewer, Bradley Glenn; Ms from University of Louisville, 2002, 51 pages http://wwwlib.umi.com/dissertations/fullcit/1410575
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Smokeless Tobacco Cessation with Nicotine Replacement: a Randomized Clinical Trial (tobacco Cessation) by Boyle, Raymond Gerrard, Phd from University of Oregon, 1992, 104 pages http://wwwlib.umi.com/dissertations/fullcit/9313278
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Specificity of Nicotine Dependence in Adult Smokers with Ptsd Symptoms: Does Depression Proneness Tell the Whole Story? by Thorndike, Frances Page; Ma from The American University, 2002, 110 pages http://wwwlib.umi.com/dissertations/fullcit/1410562
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The Behavioral Impact of Nicotine Withdrawal by Besheer, Joyce; Phd from The University of Nebraska - Lincoln, 2002, 82 pages http://wwwlib.umi.com/dissertations/fullcit/3045508
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The Cholinergic Actions of Some Arylalkyltri-methylammonium Analogues of Nicotine by Hirst, Maurice; Advdeg from The University of Western Ontario (canada), 1969 http://wwwlib.umi.com/dissertations/fullcit/NK04901
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The Effect of Nicotine on Ethanol Self-administration by Sharpe, Amanda Lea; Phd from Wake Forest University, the Bowman Gray School of Medicine, 2002, 133 pages http://wwwlib.umi.com/dissertations/fullcit/3043104
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The Effect of Oral Smokeless Tobacco on the Cardiovascular and Metabolic Responses in Humans during Rest and Exercise (cardiovascular Responses, Nicotine) by Van Duser, Bruce Lynn, Phd from Texas A&m University, 1991, 118 pages http://wwwlib.umi.com/dissertations/fullcit/9134016
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The Effect of Repeat Measured Doses of Nicotine upon Metabolic Rate during Rest and Low-level Activity by Marks, Bonita Louise, Phd from University of Pittsburgh, 1989, 222 pages http://wwwlib.umi.com/dissertations/fullcit/8921399
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The Effects of Nicotine on a 5-ht2a Receptor-mediated Behavioral Model of Tourette's Syndrome by Zhang, Bin; Ms from Truman State University, 2002, 124 pages http://wwwlib.umi.com/dissertations/fullcit/1410185
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The Effects of Running and Nicotine on Mood States by Boutcher, Stephen Hugh, Phd from Arizona State University, 1986, 173 pages http://wwwlib.umi.com/dissertations/fullcit/8622362
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The Pharmacology and Nicotine-induced Upregulation of Neuronal Nicotinic Alpha4beta2 Receptors by Vallejo, Yolanda F. Phd from The University of Chicago, 2002, 160 pages http://wwwlib.umi.com/dissertations/fullcit/3048430
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Treatment of Adolescent Smokers with the Nicotine Patch by Hanson, Karen Marie; Phd from University of Minnesota, 2001, 61 pages http://wwwlib.umi.com/dissertations/fullcit/3031980
Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.
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CHAPTER 5. CLINICAL TRIALS AND NICOTINE Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning nicotine.
Recent Trials on Nicotine The following is a list of recent trials dedicated to nicotine.8 Further information on a trial is available at the Web site indicated. •
Asthma Severity in Children and Environmental Agents Condition(s): Asthma Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Environmental Health Sciences (NIEHS) Purpose - Excerpt: This study measures residential exposures (indoor allergens, mold, nitrogen dioxide, nicotine) and relates exposure levels to daily symptoms (wheeze, persistent cough, chest tightness, shortness of breath) and medication use, in a population of children with physician diagnosed asthma, followed for 12 months. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00042705
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Behavioral Counseling for Alcohol Dependent Smokers (nicotine patch) Condition(s): Alcoholism; Smoking Study Status: This study is currently recruiting patients. Sponsor(s): National Institute on Alcohol Abuse and Alcoholism (NIAAA) Purpose - Excerpt: This study is to evaluate the effectiveness of a mood management intervention on abstinent alcoholic smokers with a history of major depression. The
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These are listed at www.ClinicalTrials.gov.
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second aim is to determine the effect of smoking treatments on alcohol abstinence and to identify factors associated with smoking and alcohol outcomes (e.g., more days of abstinence). A randomized, two-group design will be used to evaluate the added benefit of mood management compared to a state-of-the-art smoking cessation treatment. Treatment will consist of 8 weekly group sessions and 1, 3, 6, and 12-month follow-up. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004551 •
Behavioral Economics of Human Drug Self-Administration Condition(s): Drug Dependence Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Research Resources (NCRR) Purpose - Excerpt: The objective of this protocol is to examine the utility of behavioral economics for understanding reinforcer interactions as they pertain to drug selfadministration. In a series of 6 experiments, the researchers will attempt to quantify the effects of qualitatively different reinforcers (money, cigarettes, alcohol, nicotine gum) and their interactions. This work represents a continuation of research by this investigator in the area of addiction and pharmacology. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005765
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Behavioral/Drug Therapy for Alcohol-Nicotine Dependence (naltrexone/nicotine patch) Condition(s): Alcoholism; Smoking Study Status: This study is currently recruiting patients. Sponsor(s): National Institute on Alcohol Abuse and Alcoholism (NIAAA) Purpose - Excerpt: This study will develop a behavioral and drug relapse prevention program for individuals who are dependent on both alcohol and tobacco. The study's goal is to show that individuals receiving nicotine replacement therapy and naltrexone (Revia) with behavior therapy will have higher rates of abstinence from both smoking and drinking than individuals who do not receive the drug therapies. Individuals will be placed in a 12-week outpatient treatment program with followup assessments 1, 3, and 6 months after treatment. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000447
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Bupropion as a Smoking Cessation Aid in Alcoholics Condition(s): Alcoholism; Smoking
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Study Status: This study is currently recruiting patients. Sponsor(s): National Institute on Alcohol Abuse and Alcoholism (NIAAA) Purpose - Excerpt: The purpose of this study is to test the use of time-released bupropion (Wellbutrin) in patients receiving treatment for alcohol abuse/dependence as an aid to stop smoking. Patients will receive either a time-released bupropion or placebo. Both groups will receive nicotine replacement therapy during the 9 week study. A final followup assessment will be conducted 6 months from the start of treatment. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00044434 •
Centralized Telephone Outreach to Assist Smoking Cessation Among Veterans Condition(s): Smoking; Smoking cessation Study Status: This study is currently recruiting patients. Sponsor(s): Department of Veterans Affairs; Department of Veterans Affairs Health Services Research and Development Service Purpose - Excerpt: Smoking cessation interventions including behavioral and pharmacological components have been demonstrated to be both effective and costeffective. Although there is a high prevalence of smoking and smoking-related disorders among veterans who use VA medical centers for health care, rates of identification of tobacco use and provision of brief and/or intensive smoking cessation services are suboptimal. Telephone outreach (TO) may serve to increase access to counseling and medications to assist smoking cessation. From the standpoint of health systems, TO provides the opportunity for centralized oversight and quality assurance, economy of scale, and dissemination strategies that are practical to implement. At the provider level, TO addresses barriers to delivery of services such as limited time and skills. From the standpoint of the smoker, attractions of TO include accessibility, convenience, and privacy. The objectives of the study are to: 1) determine if TO increases successful quitting among veterans who smoke, compared to the distribution of written self-help materials; and 2) determine the cost-effectiveness of TO for smoking cessation for veterans who smoke. The study involves a population-based sample of veterans in VISN 13 who use one of the five Network VAMCs for primary care. Eight hundred smokers will be recruited and randomly assigned to 1) written self-help materials + TO, or 2) written self-help materials alone. The structured TO intervention protocol is based on the California Smokers' Helpline, which has been extensively evaluated by Dr. ShuHong Zhu, a co-investigator on this project. The behavioral intervention protocol includes follow-up calls scheduled in a relapse-sensitive fashion. Use of nicotine replacement therapy (NRT) is encouraged, and prescriptions facilitated. Data will be collected at baseline, 3 months, and 12 months by telephone. Information on demographic characteristics, medical and mental health histories, smoking history, intervention, and use of clinical services for smoking cessation will be included. Cost data will be calculated from administrative databases, and will include 1) written materials, 2) counseling (personnel time, equipment, space), and 3) medications. The primary outcome will be continuous abstinence from smoking since the subject's initial quit date, measured 12 months following intervention. Secondary analyses will evaluate 3 month and 12 month point prevalent abstinence from smoking, quit attempts, and a
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formal cost-effectiveness analysis that will include total costs, total and marginal effects and cost-effectiveness ratios (average cost/quit and average cost/marginal quit) for TO and SH interventions. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00012948 •
Combination Nicotine Replacement for Alcoholic Smokers Condition(s): Smoking; Alcoholism Study Status: This study is currently recruiting patients. Sponsor(s): National Institute on Alcohol Abuse and Alcoholism (NIAAA) Purpose - Excerpt: The overall objective of the study is to develop recommendations for treatment programs to help alcoholic smokers to stop smoking. A sample of 175 alcohol dependent cigarette smokers will be recruited from the community and treated in a 6month outpatient alcohol and tobacco treatment program. The 175 patients will be divided into two groups. One group will receive an active nicotine patch and active nicotine gum. The other group will receive an active nicotine patch and placebo nicotine gum. Followup assessments will be conducted for 1-year from the beginning of treatment. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00064844
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Combinations of Pharmacologic Smoking Cessation Treatments Condition(s): Smoking Study Status: This study is currently recruiting patients. Sponsor(s): Department of Veterans Affairs Medical Research Service Purpose - Excerpt: The purpose of this study is to test the effectiveness of a combination of the drugs bupropion and mecamylamine along with a nicotine patch as a therapy for smoking cessation. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00018187
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Electrophysiologic Measures of Treatment Response in Alzheimer Disease Condition(s): Alzheimer Disease Study Status: This study is currently recruiting patients. Sponsor(s): Department of Veterans Affairs Medical Research Service
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Purpose - Excerpt: The main purpose of this study is to determine the electrophysiological effects of cholinergic therapy (cholinesterase inhibitors and transdermal nicotine) in Alzheimer disease. The attempt will be to locate electrophysiological markers and predictors of cognitive and clinical treatment response. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00018278 •
Facilitating Implementation of the PHS Smoking Cessation Guideline Condition(s): Smoking Study Status: This study is currently recruiting patients. Sponsor(s): Department of Veterans Affairs; Department of Veterans Affairs Health Services Research and Development Service Purpose - Excerpt: The adverse impact of tobacco use on disease prevalence and health care costs is well documented. Hence, finding effective ways to reduce tobacco dependence is an essential component of improving the outcomes, quality and efficiency of VHA care. The U.S. Public Health Service (PHS) Smoking Cessation Clinical Practice Guideline provides specific recommendations for treating tobacco dependence. Despite their strong evidence base, however, these recommendations have not been fully integrated into clinical practice within the VHA. Recent data suggest that logistical difficulties associated with identifying and linking smokers with appropriate treatments may explain why the PHS Smoking Cessation Guideline has not been more broadly implemented. The primary objective of this study is to assess the effectiveness of an intervention for increasing the rate of tobacco dependence treatment in a population of smokers identified through the VA Pharmacy Benefits Management database. Secondary objectives of this study include (1) assessing the effect of the intervention on smoking cessation rates, and (2) developing options for overcoming potential barriers to broad implementation of the strategies. The effectiveness of the intervention will be evaluated using a multi-center, randomized, controlled trial. Veterans receiving a prescription for transdermal nicotine, nicotine gum, or bupropion for smoking cessation in the past year at one of the participating VHA facilities (as determined from Pharmacy Benefits Management records) will be eligible for the study. A total of 2,400 eligible veterans selected from eight test sites will be randomly assigned to one of two groups: (1) patient phone call and tailored, computerized prompt to providers (intervention), or (2) usual care (control). The primary outcome is the proportion of patients receiving pharmacological or other smoking cessation treatment in the six month follow-up period, as assessed from VA pharmacy and outpatient data files. All patients will be recruited to a brief phone interview six months postintervention to gather secondary outcome measure data related to smoking status, quit history, and use of smoking cessation assistance. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00057070
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High-Dose Versus Regular-Dose Nicotine Patch for Nicotine Dependence in Individuals with Schizophrenia or Schizoaffective Disorder - 1 Condition(s): Tobacco Use Disorder Study Status: This study is currently recruiting patients. Sponsor(s): National Institute on Drug Abuse (NIDA) Purpose - Excerpt: High Dose Versus Regular Dose Nicotine Patch for Nicotine Dependence in Individuals with Schizophrenia or Schizoaffective disorder Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00046813
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How the loss of Dopamine and Dopamine-Restoring Medicines Affect Movement Performance Condition(s): Parkinson Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Neurological Disorders and Stroke (NINDS) Purpose - Excerpt: This study has two purposes: 1) to understand the effect of a decline of dopamine in the brain during normal aging and in patients with Parkinson's disease, and 2) to investigate how medicines used to treat Parkinson's disease improve movement performance in patients. Patients with Parkinson's disease have difficulty performing precise finger movements, mainly because of a dramatic decrease of a substance called dopamine in parts of the brain. Medicines such as levodopa, which help restore dopamine levels, can greatly improve function; however, little is known about how these drugs work. In normal aging, dopamine decreases slightly in certain parts of the brain, but the importance of this decline is poorly understood. This study may provide new information about Parkinson's disease and normal aging that might lead to better treatment strategies. Patients with mild to moderate Parkinson's disease and healthy volunteers 21 years of age and older may be eligible for this study. All participants must be right-handed. All candidates will be screened with a medical history and physical and neurological examinations, including memory tests and mood examination. Brain function will be studied using functional magnetic resonance imaging (fMRI) study and positron emission tomography (PET). Participants may be asked to stop using medications that can affect the central nervous system, such as sleeping pills or drugs for depression or anxiety, for 1 week before each study visit. Patients with Parkinson's disease may also be asked to stop using antiparkinsonian medications at least 12 hours before each visit. In addition, all participants will be asked to abstain from alcoholic beverages at least 24 hours before the fMRI and PET scans, and from nicotine and caffeine for at least 12 hours before the scans. Participants will have fMRI, which uses a strong magnetic field and radio waves to create images of the brain. The subject lies on a table in a tunnel-like cylinder (the scanner) for 1 to 2 hours, lying still for 5 to 15 minutes at a time. He or she can communicate with the technician or researcher at all times during the test through an intercom system. Scans will be done while the subject is at rest and while he or she is performing finger movements. The movements involve pushing five buttons on a box-each button every 3 seconds on average in a specific order. Patients with Parkinson's disease will be studied off- and then on- medications that restore the levels of levodopa in the brain. Some participants
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may be asked to undergo a PET scan on a separate visit. A PET scanner is a doughnutshaped machine similar in appearance to a CT (computed tomography) scanner. PET scans detect radioactivity used to provide information on brain activity. Before the test begins, subjects are given a dose of carbidopa-a medicine that increases the amount of levodopa in the brain. A catheter (thin, plastic tube) is then inserted into an arm or wrist vein, and a radioactive form of levodopa called 18Fluorodopa is injected through the catheter. A moldable plastic mask with large openings for eyes, nose, and mouth is placed on the face to help keep the head still during scanning. The total scan time is 2 hours or less. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00040196 •
Imaging of Brain Receptors in Healthy Volunteers and in Patients with Schizophrenia Condition(s): Schizophrenia Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: This study will use single photon emission computed tomography (SPECT) to study brain nicotine receptors (proteins on the surface of brain cells) in healthy subjects and in patients with schizophrenia. Autopsy findings in patients with schizophrenia show changes in their nicotine receptors. This study will use SPECT to look at these receptors in living schizophrenia patients and compare them with those in healthy subjects. The following individuals between 21 and 50 years of age (or between 21 and 80 years of age for Group 1 only) are eligible for this study: healthy non-smokers (Group 1); schizophrenia patients who smoke (Group 2); schizophrenia patients who do not smoke (Group 3); healthy smokers (Group 4); healthy non-smokers (Group 5). Patients with schizophrenia must be taking olanzapine (Zyprexa) or risperidone (Risperdal) for at least 6 months. All candidates will be screened at the first visit. Group 1 participants will have three more visits; Groups 2 through 5 will have two more visits. Visit 1 All participants will be screened with physical and neurological examinations; blood and urine tests; and neuropsychological tests to assess their ability to learn and remember words and numbers, to pay attention, and to quickly perform motor tasks, such as putting pegs into a piece of wood. In addition, they will have an eye movement test and event-related potential testing. For the eye test, the subject sits in a chair and leans forward with the chin on a chin rest. A band is tied around the head and very small amounts of invisible (infrared) light are shined into the eyes. The light is reflected back and measured. Wire electrodes are placed around the area of the eye and cheek to monitor eye blinks and eye movements. Subjects are asked to follow a light with their eyes and to look away from a light. For event- related potential testing, electrodes are placed on the scalp, forehead and cheeks, and brain activity is recorded while the subject identifies particular pictures and sounds. Visit 2 (and Visit 3 for Group 1) Participants will have a SPECT scan. On the night before the scan, the day of the scan, and for 4 days after the scan, subject take an oral dose of potassium iodide to protect the thyroid gland from the radioactive tracer used in the SPECT procedure. (Individuals allergic to potassium iodide will take potassium perchlorate instead.) For the SPECT scan, small radioactive markers containing 99mTc are glued to the subject's head. Two catheters (thin, flexible tubes) are placed in veins in the arms to inject the radioactive tracer [123I]5-I-A-85380 and to draw blood samples. During the scan, the subject lies on a bed
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with his or her head held still with a headholder. The scans are taken over a 9-hour period after injection of the tracer injection. An electrocardiogram, respiration, and blood pressure measures are taken before injection of [123I]5-I-A-85380, then 5 minutes after the injection, and again 30 to 60 minutes after the injection. Breath samples are collected every 60 minutes. Blood and urine samples are collected 5 to 6 hours after starting the scan. Group 1 subjects will have a second SPECT scan within 4 weeks of the first. Visit 3 (Visit 4 for Group 1) Participants will have a magnetic resonance imaging (MRI) scan. For this procedure, the subject lies on a table that slides into a narrow metal cylinder with a strong magnetic field for the scan. The scanner uses a magnetic field and radio waves to produce images that show structural and chemical changes in tissues. The test lasts up to 1 hour. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00061789 •
Naltrexone and Patch for Smokers Condition(s): Smoking Study Status: This study is currently recruiting patients. Sponsor(s): Department of Veterans Affairs Medical Research Service Purpose - Excerpt: The aim of this study is to investigate the effects of naltrexone, alone and combined with nicotine patch, on responses of smokers to smoking cues after 10 hours of tobacco deprivation. Smokers who are not seeking treatment will be assigned to one of six conditions: They will receive either 50 mg of naltrexone or a placebo pill, and also will wear a nicotine patch that has 0, 21, or 42 mg of nicotine during the tobacco deprivation period. Both the day before the medication and deprivation and at the end of 10 hours of deprivation all will be exposed to lit cigarette cues in the laboratory. Effects of the medications will be assessed on withdrawal measures, urge to smoke, psychophysiological measures, and the topography of smoking three test cigarettes. Studies such as these can help to identify potential interventions for tobacco cessation or withdrawal, and thereby could result in less suffering and mortality. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00018213
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Nicotine Replacement Treatment for Pregnant Smokers Condition(s): Nicotine Dependence; Pregnancy Study Status: This study is currently recruiting patients. Sponsor(s): Oncken, Cheryl, MD; Hartford Hospital; General Clinical Research Center at UCONN Health Center; Duke University Purpose - Excerpt: Smoking during pregnancy is an important modifiable cause of poor pregnancy outcomes. Even with augmented behavioral interventions, smoking cessation rates in pregnancy trials rarely exceed 20%. These low quit rates may be due to inadequate treatment of the physical dependence on nicotine. Indeed, medications, which may help to reduce nicotine withdrawal symptoms, are a first-line treatment for smoking treatment in non-pregnant smokers. However, little information is available on
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the safety or efficacy of medications to treat pregnant smokers. The purpose of this trial is to evaluate the safety and effectiveness of 2 mg nicotine gum in promoting smoking cessation during pregnancy. The design is a randomized, placebo controlled trial where subjects are randomized to nicotine gum (6 weeks ad libitum use followed by a 6 week taper) or a matching placebo. Women who are doing well at the end of the trial will also be offered gum post-partum for relapse prevention. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00064948 •
Quit Smoking Condition(s): Smoking Study Status: This study is currently recruiting patients. Sponsor(s): Department of Veterans Affairs Medical Research Service Purpose - Excerpt: This protocol evaluates the efficacy of combining pharmacologic treatments for smoking cessation, entailing the use of the nicotine skin patch with the nicotinic antagonist mecamylamine, with a specific behavioral therapy designed to inhibit the smoking urge. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00018161
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Single Photon Emission Computed Tomography to Study Receptors in Parkinson's Disease Condition(s): Parkinson Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Neurological Disorders and Stroke (NINDS) Purpose - Excerpt: This study will use single photon emission computed tomography, or SPECT (see below), to examine brain nicotine receptors in evaluating the role of a chemical called acetylcholine in memory and other problems in Parkinson's disease (PD). Acetylcholine acts by binding to these nicotine receptors. Healthy normal volunteers and patients with Parkinson's disease 40 years of age and older, with or without dementia, may be eligible for this study. Candidates will be screened with physical and neurological examinations, a pen and paper test of memory and other mental functions, blood tests, and, for women of childbearing potential, a pregnancy test. Patients with cognition problems will have more intensive mental function tests. All participants will undergo the following procedures: - Magnetic resonance imaging (MRI): This test uses a strong magnetic field and radio waves to show structural and chemical changes in the brain. During the scan, the subject lies on a table in a narrow cylinder (the scanner). The time required in the scanner is about 1 hour, during which the subject is asked to lie very still for 10 to 15 minutes at a time. He or she can speak with a staff member via an intercom system at all times during the procedure. - SPECT: This nuclear medicine test produces a picture of the receptors in the brain. On the night
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before the scan, the day of the scan, and for 4 days after the scan, subjects take an oral dose of potassium iodide to protect the thyroid gland from the radioactive tracer used in the SPECT procedure. (People allergic to potassium iodide will take potassium perchlorate instead.) Before the scan, small radioactive markers containing 99Tc are glued to the subject's head. Two catheters (thin, flexible tubes) are placed in veins in the arms to inject the radioactive tracer [123I]5-I-A-85380 and to draw blood samples. Another catheter is placed in an artery in the wrist to draw arterial blood samples. During the scan, the subject lies on a bed with his or her head held still with a head holder. The scans are taken over a 6-hour period after injection of [123I]5-I-A-85380. An electrocardiogram, respiration, and blood pressure measures are taken before the tracer is injected, then 5 minutes after the injection, and again 30 to 60 minutes after the injection. Blood and urine samples are collected 5 to 6 hours after starting the scan. Participants are asked to urinate at least every 2 hours for 12 hours after injection of [123I]5-I-A-85380 to decrease radiation exposure. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00058721 •
Smoking Cessation Treatment w Transdermal Nicotine Replaceme Therapy - 1 Condition(s): Tobacco Use Disorder Study Status: This study is currently recruiting patients. Sponsor(s): National Institute on Drug Abuse (NIDA); New York University Purpose - Excerpt: CTN-0009 Smoking Cessation Treatment w/ Transdermal Nicotine Replacement Therapy Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00067158
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Susceptibility to Breast Cancer Condition(s): Breast Cancer; Healthy Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: This study will explore whether different forms, or variants, of genes are related to a person's risk of developing breast cancer. The genes that are looked at have no clinical significance today, and thus will not impact your personal healthcare at this time. However, these results may help researchers better understand why some people develop breast cancer and others do not. The study will try to determine: if people with breast cancer have different gene variants from people without the disease; if these genetic differences influence a person's susceptibility to breast cancer when they are exposed to certain environmental substances, such as nicotine and estrogen; and if breast cancer that occurs in families is related to a grouping of these variants. The study will also look for certain proteins, cells, or other substances in fluid aspirated (by the use of gentle suction; no needles) from the nipple that might represent a pattern, or "fingerprint," indicating increased risk for breast cancer. Study participants will complete questionnaires on cancer risk factors, diet, and family history. A small blood
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sample (3 tablespoons) will be drawn for study of genetic differences between people with breast cancer and people who are cancer-free. Nipple aspirations, a noninvasive method to obtain fluid from a women's breast, will be attempted 4 to 6 times, over a 4 - 6 week period. For this procedure, the subject places a warm moist towel over the breasts for about 20 minutes. The breasts are then cleansed with a rubbing alcohol pad. The subject compresses the breast with both hands and a small plastic cup is inverted over the breast. Suction is applied to a small syringe (no needles) attached to the cup for about 15 seconds. The procedure may be repeated up to 5 times on each breast. Any drops of fluid obtained from the nipple will be collected in a glass tube. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004565 •
Timing of Smoking Intervention in Alcohol Treatment (nicotine patch) Condition(s): Alcoholism; Smoking Study Status: This study is currently recruiting patients. Sponsor(s): National Institute on Alcohol Abuse and Alcoholism (NIAAA) Purpose - Excerpt: This study will attempt to determine the best time to begin a smoking cessation program in individuals who undergo intensive treatment for alcohol dependence. The goal of this trial is to determine whether a smoking cessation program is more effective if it occurs at the same time as or after treatment for alcohol dependence. The study also will attempt to determine the effect of smoking cessation programs on the outcome of treatment for alcohol dependence. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000444
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Tobacco Dependence in Alcoholism Treatment (nicotine patch/naltrexone) Condition(s): Alcoholism; Smoking Study Status: This study is currently recruiting patients. Sponsor(s): National Institute on Alcohol Abuse and Alcoholism (NIAAA) Purpose - Excerpt: The purpose of this study is to determine the effectiveness of naltrexone (Revia) in reducing drinking and smoking in patients with both nicotine and alcohol dependence. Individuals will be randomly assigned to a 12-week trial of a fixed daily dose of either naltrexone (Revia) and nicotine replacement patch or placebos. All individuals will receive weekly coping skills and smoking-cessation behavioral therapy. Followup interviews will be conducted 3 and 6 months after treatment to determine smoking and drinking status and persistence of any dependence symptoms. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000437
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Combined Nortriptyline and Transdermal Nicotine for Smoking Cessation Condition(s): Smoking Study Status: This study is no longer recruiting patients. Sponsor(s): Department of Veterans Affairs Medical Research Service Purpose - Excerpt: Treatment of smokers with a tricyclic antidepressant, nortriptyline, can reduce tobacco withdrawal symptoms and increases long term cessation rates when combined with transdermal nicotine and a behavioral cessation programs. The study is a placebo-controlled, randomized, parallel group trial in which smokers aged 18-70 will be subject to the combination of oral and patch treatments. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00018148
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Effects of Labetalol on Nicotine Administration in Humans - 14 Condition(s): Tobacco Use Disorder Study Status: This study is completed. Sponsor(s): National Institute on Drug Abuse (NIDA); University of Minnesota Purpose - Excerpt: The goals of this study is to investigate the effects of lubetalol in response to intravenous nicotine Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000297
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Pharmacologic Intervention for Postcessation Weight Gain Condition(s): Cardiovascular Diseases; Heart Diseases; Obesity Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To test pharmacologic intervention for smoking postcessation weight gain using nicotine gum and phenylpropanolamine (PPA). Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005704
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Pharmacologic Relapse Prevention for Alcoholic Smokers Condition(s): Alcoholism; Smoking Study Status: This study is completed. Sponsor(s): National Institute on Alcohol Abuse and Alcoholism (NIAAA) Purpose - Excerpt: This study will compare the long-term use of bupropion (Wellbutrin) and placebo for reducing the rate of smoking relapse in recovering alcoholics who
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achieved initial abstinence from smoking with nicotine patch therapy. The study will also determine the cessation rate in the 8th week of treatment among recovering alcoholics using a nicotine patch. The patch dose is projected to serve as a 100-percent replacement. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000457 •
Role of Metabolites in Nicotine Dependence (1) - 1 Condition(s): Tobacco Use Disorder Study Status: This study is completed. Sponsor(s): National Institute on Drug Abuse (NIDA); University of Minnesota Purpose - Excerpt: To determine the effects of continine with or without a transdermal nicotine replacement on tobacco withdrawal symptoms. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000284
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Role of Metabolites in Nicotine Dependence (2) - 5 Condition(s): Tobacco Use Disorder Study Status: This study is completed. Sponsor(s): National Institute on Drug Abuse (NIDA); University of Minnesota Purpose - Excerpt: To determine the effects of varying doses of cotinine on cigarette selfadministration. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000288
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Role of Metabolites in Nicotine Dependence (3) - 6 Condition(s): Tobacco Use Disorder Study Status: This study is completed. Sponsor(s): National Institute on Drug Abuse (NIDA); University of Minnesota Purpose - Excerpt: To determine the effects of various doses of ondansetron transdermal nicotine replacement on tobacco withdrawal symptoms. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000289
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Role of Metabolites in Nicotine Dependence (4) - 13 Condition(s): Tobacco Use Disorder Study Status: This study is completed. Sponsor(s): National Institute on Drug Abuse (NIDA); University of Minnesota Purpose - Excerpt: To determine the effects of continine with or without a transdermal nicotine replacement on tobacco withdrawal symptoms. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000296
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Smoking Cessation in Alcoholism Treatment Condition(s): Alcoholism; Smoking Study Status: This study is completed. Sponsor(s): National Institute on Alcohol Abuse and Alcoholism (NIAAA) Purpose - Excerpt: This study is designed to increase understanding of the processes that affect the treatment outcome of individuals with both alcohol and nicotine dependence. Treatment outcome methodology will be combined with a computerized self-monitoring methodology to examine the extent to which smoking serves as a cue for alcohol craving and/or as a response to alcohol craving in treated alcoholics. Subjects will be veterans participating in the Substance Abuse Day Programs at the Newington and West Haven campuses of the VA Connecticut Healthcare System. Nonveteran women will be recruited from the community and enrolled in the day program. Subjects will be randomly assigned to one of the following two conditions: (1) intensive smoking cessation therapy (counseling plus nicotine replacement using nicotine patches) concurrent with alcohol treatment, or (2) brief smoking cessation advice concurrent with alcohol treatment. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000454
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The effects of ERT on appetitive behavior and withdrawal in short-term smoking cessation in postmenopausal females on transdermal nicotine replacement - 2 Condition(s): Tobacco Use Disorder Study Status: This study is completed. Sponsor(s): National Institute on Drug Abuse (NIDA) Purpose - Excerpt: Tobacco Cessation in Postmenopausal Women (Part II) Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00061074
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Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “nicotine” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •
For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/
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For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html
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For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/
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For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm
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For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm
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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm
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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp
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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm
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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/
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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm
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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm
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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm
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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm
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For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm
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For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials
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CHAPTER 6. PATENTS ON NICOTINE Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “nicotine” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on nicotine, we have not necessarily excluded non-medical patents in this bibliography.
Patents on Nicotine By performing a patent search focusing on nicotine, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We
9Adapted
from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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will tell you how to obtain this information later in the chapter. The following is an example of the type of information that you can expect to obtain from a patent search on nicotine: •
Agonist-antagonist combination to reduce the use of nicotine and other drugs Inventor(s): Rose; Jed E. (Venice, CA), Levin; Edward D. (Los Angeles, CA) Assignee(s): Schaap; Robert J. (Los Angeles, CA) Patent Number: 5,574,052 Date filed: April 29, 1994 Abstract: A method of treating and reducing a drug dependency such as a nicotine dependency is provided. The method comprises initially administering to a subject a drug, such as nicotine or another agonist of the drug in an amount which would normally provide the desired pharmacologic effects and at least partially satiate the needs for the drug by a user. The method also comprises administering to the subject an antagonist to the drug or its other agonist in an amount sufficient to at least partially block the pharmacologic effects of the drug or its other agonist while there is a substantial amount of the drug or other agonist present in the system of the user. In one embodiment of the invention, the drug and the antagonist are administered substantially simultaneously so as to occupy a substantial portion of the receptors of the user for that drug thereby blocking or attenuating the effects of any further intake of the drug or other agonist. In another embodiment, the drug or its other agonist is first administered and the antagonist is self-administered by a subject in a manner which mimics the use of the drug thereby counter-conditioning the drug user to the stimuli associated with the normal administration of the drug. The invention further provides a method of therapeutically treating psychophysiologic diseases and disorders involving neuronal dysregulation. The method additionally provides a pharmacologic composition for the treatment and reduction of drug dependence. Excerpt(s): This invention relates in general to certain new and useful improvements in methods and compositions for treating and reducing drug dependency and for therapeutically treating psychophysiologic diseases and disorders involving neuronal dysregulation and more particularly, to methods and compositions of the type stated which rely upon the administration of a combination of a drug or another agonist and an antagonist to the drug. This invention was made with the support of the Veterans Administration of the United States government. The government has certain rights in this invention. The substantial use of drugs and particularly, the widespread abuse of drugs has led to increased incidence of health problems and has even largely contributed to significant increases in crime. It has been well established that the intake of the drug nicotine through tobacco smoking has resulted in various adverse health conditions. While the use of drugs, such as nicotine, do not necessarily lead to increased incidence of crime, use of this drug and similar related drugs does present significant health problems. Web site: http://www.delphion.com/details?pn=US05574052__
Patents 383
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Agonists and antagonists to nicotine as smoking deterrents Inventor(s): Abood; Leo G. (45 Crandon Way, Rochester, NY 14618) Assignee(s): none reported Patent Number: 4,966,916 Date filed: March 20, 1989 Abstract: Agonists and antagonists to nicotine are used as smoking deterrents.The nicotinic antagonists have the following structural requirements:(1) Aromatic, cycloalkyl, and heterocyclic carbamic acid esters of di- and trialkylaminoalkyl alcohols.(2) Aromatic, cycloalkyl, and heterocyclic thiocarbamic acid esters of di- and trialkylaminoalkyl alcohols.(3) Aromatic, cycloalkyl, and heterocyclic carboxylic acid esters of di- and trialkylaminoalkyl alcohols.(4) Aromatic, cycloalkyl, and heterocyclic carboxylic acid esters of heterocyclic amino alcohols.(5) Lobelia alkaloids: lobeline, lobelanine, and lobelanidine.The nicotinic agonists (nicotine-like) have the following structural requirements:(1) methylcarbamic acid esters of di- and trialkylaminoalkyl alcohols.(2) methylthiocarbamic acid esters of di- and trialkylaminoalkyl alcohols. Excerpt(s): The field of the invention is tobacco and antismoking products (deterrents) and the present invention is particularly concerned with agonists and antagonists to nicotine. The state of the art of tobacco smoking deterrents may be ascertained by reference to U.S. Pat. Nos. 4,276,890 and 4,311,691 of FICHERA and U.S. Pat. No. 4,579,858 of FERNOE et al, the disclosures of which are incorporated herein by reference. Fernoe et al are aware of the prior art nicotine containing chewing gums as disclosed in U.S. Pat. Nos. 865,026; 940,521; 3,877,468; 3,901,248 and 3,845,217 and state that it seems particularly difficult to find other smoking substitutes equivalent to or as effective as these nicotine containing chewing gums. U.S. Pat. No. 4,579,858 discloses a smoking substitute composition for application directly into the nose, consisting essentially of an aqueous solution of nicotine or a physiologically acceptable acid addition salt thereof, having a pH value of 2 to 6, containing 10 to 0.5% w/v of nicotine calculated as the free base, containing a nasally-acceptable thickening agent, having a viscosity not less than 100 centipose, and having about 0.5 to 5 mg nicotine per every 0.05 to 0.5 ml thereof and a method of diminishing the desire of a subject to smoke, which comprises the step of administering to the subject intranasally this smoking substitute composition. Web site: http://www.delphion.com/details?pn=US04966916__
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Anti-nicotine agent prepared from a saccharide and rosin or turpentine Inventor(s): Mitsui; Hisashi (Yokohama, JP) Assignee(s): Ozawa; Miya (Yokohama, JP) Patent Number: 4,166,847 Date filed: March 2, 1977 Abstract: An anti-nicotine agent including the combination of a monosaccharide or disaccharide, acetic acid or glacial acetic acid, rosin or turpentine, and an aqueous 28% ammonia solution. Excerpt(s): This invention relates to a new anti-nicotine agent. The adverse effects of nicotine on the human system which are occasioned by habitual smoking have aroused grave public concern in recent years. In spite of such circumstances, no proper anti-
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nicotine agent for effectively inhibiting nicotinism has been made available. A primary object of this invention, therefore, is to provide an effective anti-nicotine agent. Web site: http://www.delphion.com/details?pn=US04166847__ •
Apparatus for the controlled delivery of nicotine, process for the production thereof and use thereof Inventor(s): Jaeger; Halvor (New-Ulm, DE), Hoffmann; Hans-Ranier (Neuwied, DE), Meconi; Reinhold (Neuwied, DE), Klein; Robert-Peter (Neuwied, DE) Assignee(s): LTS Lohmann Therapie-Systeme GmbH & Co. KG (Neuwied, DE) Patent Number: 5,411,739 Date filed: May 3, 1994 Abstract: The invention relates to an apparatus for the controlled delivery of nicotine with a contact adhesive nicotine reservoir with uniform or irregular distribution of the nicotine, characterized in that the reservoir is produced using a hot melt contact adhesive with a processing temperature of 40.degree. to 80.degree., preferably 40.degree. to 60.degree. and in particularly preferred manner 40.degree. to 55.degree. C., a process for the production thereof and the use of the apparatus in human or veterinary medicine, particularly for stopping people smoking, or as a respiratory, contact or stomach poison in pest control. Excerpt(s): The invention relates to an apparatus for the controlled delivery or release of nicotine with a pressure sensitive adhesive nicotine reservoir with a uniform or irregular distribution of the nicotine, processes for the production thereof and the use thereof. Nicotine-containing plasters, particularly for the purpose of stopping smoking are known. Thus, for example, DE-OS 34 38 284 (Tilly) describes a nicotine-containing depot plaster. It is proposed in "Drug and Alcohol Dependence" vol. 13, 1984, pp. 209-213 by J. E. Rose, N. E. Jarvic and K. D. Rose to supply nicotine transdermally to nicotinedependent patients, in order to prevent habitual smokers, who are nicotine-dependent, from inhaling carcinogenic substances. Tests have been carried out with aqueous nicotine solutions, which were protected by means of a thin polyethylene coating from evaporating following application to the skin and it was found that nicotine permeates the skin and the same nicotine level as through smoking can be obtained by means of transdermal nicotine administration. Etscorn proposes in U.S. Pat. No. 3,597,961 a simple nicotine plaster for the purpose of enabling people to stop smoking, in which the nicotine, which is present in a cavity in a plaster and optionally covered by a nicotinepermeable membrane, can be brought into contact with the skin, so as to permit the permeation of the nicotine into the human body and to combat nicotine dependence of smokers. Web site: http://www.delphion.com/details?pn=US05411739__
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Battery powered nicotine vaporizer Inventor(s): MacDonald; Angus C. (3335 Fernside Blvd., Alameda, CA 94501), Claytor, III; William G. (San Francisco, CA) Assignee(s): MacDonald; Angus Collingwood (Alameda, CA) Patent Number: 5,564,442 Date filed: November 22, 1995 Abstract: A nicotine vaporizer is provided with a housing with a battery compartment size for a pair of AA dry cells and a compartment for containing tobacco, a lower portion of which has a hole for passing tobacco into a firebox cavity arranged there below and shiftable from a tobacco receiving to a tobacco burning position. Electric coil means are set in the firebox cavity and energized to bring the tobacco to combustion temperature. A mouth piece equipped suction tube extends into the housing so that as air is withdrawn through the suction tube with the coil energized the tobacco will combust as to the microcharge contained in the firebox cavity. The microcharge of tobacco is of such volume that no more smoke is created than can be processed by the lungs in one breath. Excerpt(s): This invention relates to tobacco smoking and more particularly to an improved apparatus and method serving to achieve the effect of smoking without releasing second hand smoke into the surrounding area. Tobacco was in use in the New World well before the arrival of Christopher Columbus. It is normally smoked in cigarettes or in a pipe or chewed or used in powder form as snuff. All of these modes of using tobacco are distasteful in some way or other, especially to non-smokers, due to second hand smoke, spitting of tobacco and its juices, etc. An important constituent of tobacco, nicotine, is also available as a drug and may be delivered in a chewable gum or as an arm patch, both by a physician's prescription. These systems for delivering the nicotine are not distasteful and they assist smokers to quit using tobacco but they are not satisfying as there is no associated pleasure as when the concentration of nicotine rises sharply in the bloodstream. The rapid transfer of any substance into the bloodstream is most quickly effected by a directed injection and inhalation is a close second, with eating and transdermal absorption tied for third place for speed of transfer. Often the rate at which the bloodstream concentration rises is critical to the perceived effect. This is why it is often difficult for cigarette smokers to switch to any other form of nicotine delivery. Cigarette smoke, unlike pipe or cigar smoke, is fully inhaled into the lungs so the effect is felt almost immediately. An unfortunate side effect of smoking cigarettes is that the smoker inhales into the lungs tars and other products of combustion which are subsequently exhaled as "second hand smoke". There is ample documentation that the smoking of cigarettes as well as prolonged exposure to second hand smoke makes the human body vulnerable to emphysema, heart disease and cancer. Electric heating of tobacco for smoking is well known. U.S. Pat. No. 5,269,327 issued Dec. 14, 1993 to Mary E. Counts, et al. discloses a cigarette shaped article containing a plurality of charges of tobacco flavored medium equal to an average number of puffs per cigarette. The charges are individually heated electrically as the smoker puffs on the unit. The complexity of this device as well as the need for specialized tobacco charges are serious practical drawbacks. Web site: http://www.delphion.com/details?pn=US05564442__
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Bridged nicotine compounds for use in the treatment of CNS pathologies Inventor(s): Crooks; Peter A. (Lexington, KY), Dwoskin; Linda P. (Lexington, KY), Xu; Rui (New York, NY), Grinevich; Vladimir P. (Lexington, KY) Assignee(s): University of Kentucky Research Foundation (Lexington, KY) Patent Number: 6,503,922 Date filed: August 30, 2001 Abstract: Pharmaceutical compounds comprising bridged nicotine analogs of Noctylnicotinium iodide (NONI) having selective antagonist properties at.alpha.3.beta.2containing nicotinic receptor subtypes, and compositions containing these compounds. The compounds and compositions are used to treat central nervous system pathologies. Excerpt(s): This invention relates to bridged nicotine analogs of N-octylnicotinium iodide (NONI) that have selective antagonist properties at.alpha.3.beta.2-containing nicotinic receptor subtypes and to a method of using such compounds to treat central nervous system pathologies. The present invention also relates to pharmaceutical compositions containing these compounds, as well as various uses thereof. Formula (I) below shows the structure of S-(-)-nicotine (NIC), which activates neuronal nicotinic receptors evoking release of dopamine (DA) from presynaptic terminals in the central nervous system (CNS). NIC is a legal substance of dependence that produces many of its effects on the CNS, some of which may be considered to be beneficial, e.g., mood elevation, arousal and learning and memory enhancement. NIC produces its effect by binding to a family of ligand-gated ion channels, stimulation by acetylcholine (ACh) or NIC causes the ion channel to open, and cations to flux with a resulting rapid (in msec) depolarization of the target cell. Over the last 12 years, there has been a substantial increase in studies on brain nicotinic receptors. These nicotinic receptors are composed of four subunit domains: 2.alpha.,.beta.,.gamma. and.delta. or.epsilon. Neuronal nicotinic receptors are composed of only two subunits,.alpha. and.beta. and are believed to assemble with the general stoichiometry of 2.alpha. and 3.beta. Eight subtypes of the.alpha. subunit (.alpha.2 to.alpha.9) and three subtypes of the.beta. unit (.beta.2 to.beta.4) are found in CNS. The most common nicotinic receptor species in the brain is composed of two.alpha.4 and three.beta.2 subunits, i.e.,.alpha.4.beta.2. These subunits display different, but overlapping, patterns of expression in the brain. Web site: http://www.delphion.com/details?pn=US06503922__
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Cigarette holder with nicotine extractor Inventor(s): Miura; Noriyoshi (1-5, Takashimadaira 4-chome, Itabashi-ku, Tokyo, JP) Assignee(s): none reported Patent Number: 4,344,444 Date filed: November 13, 1980 Abstract: A cigarette holder having an attractive appearance and a compact structure suitable for use by ladies without any feel of reluctance, and capable of effectively removing nicotine and tar while permitting a visual check of the state of removal of nicotine and tar from the outside. A nicotine extractor made of a colored material, for removing the nicotine and tar by impact caused by collision of smoke, is fitted in a cigarette holder body made of a transparent material. When the colored nicotine
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extractor has become invisible from the outside of the cigarette holder body due to accumulation of nicotine and tars, the cigarette is no longer usable and can be discarded. Excerpt(s): The present invention relates to a compact cigarette holder having a superior effect in removing nicotine and tars. Recently, the habit of smoking has become popular also among ladies, which poses a problem that the mother and the embryo are adversely affected by nicotine and tar contained in the tobacco smoke. Various cigarette holders capable of removing nicotine and tar have been proposed already. These cigarette holders, however, are generally expensive and large-sized, and have appearance suitable for men, so that ladies are usually somewhat reluctant to use these pipes. Web site: http://www.delphion.com/details?pn=US04344444__ •
Colonic delivery of nicotine to treat inflammatory bowel disease Inventor(s): Sandborn; William (Rochester, MN), Rhodes; John (Cardiff, GB) Assignee(s): Mayo Foundation for Medical Education and Research (Rochester, MN) Patent Number: 6,166,044 Date filed: March 23, 1999 Abstract: A method is provided to treat inflammatory bowel disease by locally administering to the colon an effective amount of nicotine or a pharmaceutically acceptable salt thereof, preferably via formulations adapted for delayed oral release or rectal administration. Further provided is a novel formulation for the oral administration of nicotine comprising a polyacrylic polymer complexed with nicotine. Excerpt(s): Inflammatory bowel disorders or diseases (IBD) encompass a spectrum of overlapping clinical diseases that appear to lack a common etiology. IBD, however, are characterized by chronic inflammation at various sites in the gastrointestinal (GI) tract. Illustrative IBD are regional enteritis (or Crohn's disease), idiopathic ulcerative colitis, idiopathic proctocolitis, pouchitis and infectious colitis. Symptoms of IBD may include persistent diarrhea, abdominal pain, fever, weight loss, joint pain, skin lesions and general fatigue. The inflammatory conditions of ulcerative colitis are confined to the colon, unlike Crohn's disease which can involve any portion of the intestinal tract. Current treatment for IBD includes oral, IV and colonically administered corticosteroids and oral and colonically administered 5-aminosalicylic acid (Edsbacker et al., Gastroenterology 104:A695 (1993); Greenberg et al., NEJM 317:1625-29 (1987). cyclosporin is another treatment for IBD, but this is limited to oral administration since colonic administration was not efficacious; (Gastroenterology 1994, 108:1429-1435). Several types of colonic drug delivery systems are currently available, including enemas (Sutherland et al., Med. Clin. North Amer., 74:119 (1990)); rectal foams (Drug Ther. Bull., 29:66 (1991)); and delayed oral release formulations in the form of enteric-coated capsules which disintegrate at pH7 in the terminal ileum (Schroeder et al., NEJM, 317:1625 (1987)). Web site: http://www.delphion.com/details?pn=US06166044__
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Composition and method for treating nicotine craving in smoking cessation Inventor(s): Callaway; Enoch (Tiburon, CA) Assignee(s): Regents of the University of California (Oakland, CA) Patent Number: 5,480,651 Date filed: March 15, 1994 Abstract: A method for relieving craving in a nicotine-habituated patient and a composition for treating the patient is provided. The composition administered has a non-specific acetylcholine agonist and a muscarinic agonist. A particularly preferred composition for relieving craving takes the form of a tablet where the first component is a water soluble physostigmine and the second component is a water soluble scopolamine. Patients treated have reported a slight increase in alertness and a diminished craving for nicotine. Excerpt(s): The present invention generally relates to treating smoking withdrawal symptoms, and more particularly to a composition useful in relieving craving in a nicotine-habituated patient abstaining from or reducing nicotine intake. The statistical risk of dying from lung cancer in the United States has doubled in the past thirty years for male cigarette smokers and has quadrupled for female cigarette smokers. Lung cancer has now displaced cardiovascular disease as the single most important cause of excess mortality among smokers. Yet, about 50 million Americans continue to smoke. The benefits for smoking cessation are many, and are summarized in a publication entitled "The Health Benefits of Smoking Cessation: A Report of the Surgeon General, 1990", available from the Office on Smoking and Health, Center for Disease Control, Rockville, Md. Among the benefits summarized are that within twenty-four hours the chance of a heart attack decreases, within about two weeks to three months lung function increases up to thirty percent, and in one year the excess risk of coronary heart disease becomes half that of a smoker. Web site: http://www.delphion.com/details?pn=US05480651__
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Composition for drug delivery comprising nicotine or a derivative thereof and starch microspheres and method for the manufacturing thereof Inventor(s): Albrechtsen; Sten (Hillerod, DK), Orup-Jacobsen; Lene (Gentofte, DK), Hansen; Jens (Allerod, DK), Mollgaard; Birgitte (Virum, DK) Assignee(s): Pharmacia and UpJohn AB (Helsingborg, SE) Patent Number: 5,939,100 Date filed: August 26, 1996 Abstract: A powdery pharmaceutical composition comprising nicotine or a derivative thereof and starch microspheres. The starch microspheres are preferably degradable epichlorhydrin cross-linked starch microspheres. The average diameter of the microspheres is from around 1.mu.m to around 200.mu.m, preferably around 45.mu.m. The invention also encompasses a method for manufacturing a powdery pharmaceutical composition comprising nicotine and starch microspheres. The invention further comprises a method of diminishing the desire of a subject to use tobacco which comprises the step of administering to the subject the above powdery pharmaceutical composition.
Patents 389
Excerpt(s): The present invention concerns a composition for drug delivery and a method for the manufacturing thereof. Specifically the invention concerns a composition in which a drug is bound to starch microspheres. The composition according to the invention is of particular interest for nasal delivery. The composition is primarily intended as an aid in nicotine replacement therapy. A primary objective of the invention is to provide for a new and inventive pharmaceutical composition for nasal, oral, buccal or pulmonary administration of nicotine. The objective is achieved with a powdery composition comprising nicotine incorporated in degradable starch microspheres. A further objective of the invention is to provide for a method of incorporating nicotine into starch microspheres. Web site: http://www.delphion.com/details?pn=US05939100__ •
Compositions and methods for using low-swell clays in nicotine containing dermal compositions Inventor(s): Mantelle; Juan (Miami, FL), Kanios; David (Miami, FL) Assignee(s): Noven Pharmaceuticals Inc., (Miami, FL) Patent Number: 5,725,876 Date filed: May 17, 1996 Abstract: A dermal composition for transdermal administration of nicotine includes a blend of: one or more acrylic-based polymers in an amount of from about 10-90% w/w, nicotine in an amount of from about 3 to 15% w/w, and a cohesiveness increasing amount of one or more low-swell clays in an amount of from about 0.5 to 30% w/w. The low-swell clay has a swell of 3-23 mls as determined by the bentonite USP/NF swelling power test. Also disclosed is a method for producing a dermal composition and a method for increasing the cohesiveness of a nicotine containing dermal composition. Excerpt(s): The present invention relates to compositions and methods for dermal administration of nicotine. More specifically, the present invention relates to the use of low-swell clays in dermal compositions containing nicotine. The present invention also relates to a method for the dermal administration of nicotine. Dermal compositions of a drug within a polymer matrix for systemic or topical sustained released drug delivery are known in the art. One problem with drugs which are normally liquid at room temperature, such as nicotine, or drugs which have been solubilized with other liquid components, is the plasticizing effect that the liquid has on the polymer matrix in the dermal composition. Namely, the liquid can have an excessive plasticizing effect on the polymer, resulting in a composition that is "leggy or gummy." This renders the composition unsuitable for adhesion to the epidermis. Another difficulty with excessive liquidity in a dermal composition is the effect that the liquid has on the adhesiveness of the system. The use of clays in dermal compositions is also generally known in the art. These clays are generally added as fillers as described in U.S. Pat. No. 4,421,737. Clays are also described as being used in dermal compositions for increasing the adhesiveness of these compositions as described in U.S. Pat. No. 5,300,291. The objective of using clay to increase other properties, such as cohesiveness, is also broadly described in U.S. Pat. No. 5,300,291 and in copending application Ser. No. 08/447,361. None of the related art, however, is able to describe what aspect of clay controls its effect on the wear and other properties a dermal composition, especially, in relation to cohesiveness or shear resistance. Web site: http://www.delphion.com/details?pn=US05725876__
390 Nicotine
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Edible herbal compositions for relieving nicotine craving Inventor(s): Wolfson; Philip (San Anselmo, CA), Jacobs, III; Payton (Lafayette, CA), Shulgin; Alexander T. (Lafayette, CA) Assignee(s): Phytos, Inc. (San Anselmo, CA) Patent Number: 6,534,527 Date filed: June 4, 2001 Abstract: Compositions useful in relieving craving in nicotine habituated patients are provided that include an herbal component. The herbal component provides multiple nicotine agonists, one of which is anabasine. The compositions are preferably in the form of chewing gum, tablets, capsules, or lozenge. Excerpt(s): The present invention generally relates to compositions useful in relieving craving in a nicotine habituated patient who is abstaining from or reducing nicotine intake, and more particularly relates to edible compositions including an herbal component which provides multiple nicotine agonists, one of which is anabasine, but has little or no nicotine. Using 1996 data, the prevalence of cigarette smoking in the United States among adults was about 27% or 55 million people. Each year some 30% of smokers try to quit, but only about 10% are successful. The efficacy rate for formal cessation programs, defined as abstinence at one year follow-up, is between 20 and 40% of those enrolled. The most telling fact is that the majority of smokers who are successful in quitting tobacco have done so on their own. In the past ten years, 47.5% of persons attempting to quit smoking on their own were successful compared to 23.6% of those who used smoking cessation programs to quit. There have been many therapies and pharmacologic agents used to assist in smoking cessation. Nicotine delivered through gum, transdermal patches, and nasal sprays in declining dosages over time have been the principal pharmacologic strategies, i.e., a withdrawal over time minus the tar of actual cigarettes. Web site: http://www.delphion.com/details?pn=US06534527__
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Hapten-carrier conjugates for treating and preventing nicotine addiction Inventor(s): Ennifar; Sofiane (Silver Spring, MD), Fattom; Ali Ibrahim (Rockville, MD), Naso; Robert B. (Gaithersburg, MD) Assignee(s): NABI (Rockville, MD) Patent Number: 6,518,031 Date filed: February 16, 2001 Abstract: Novel hapten-carrier conjugates are capable of inducing the production of antibodies, in vivo, that specifically bind to nicotine. These conjugates comprise a nicotine hapten conjugated to an immunogenic carrier protein. The novel conjugates preserve the chirality of nicotine in its native (S)-(-) state, and have good stability properties. The conjugates are useful in formulating vaccines for active immunization, that are used to prevent and treat nicotine addiction. The antibodies raised in response to the nicotine hapten-carrier conjugate are used for passive immunization. These antibodies are administered for prevention and treatment of nicotine addiction.
Patents 391
Excerpt(s): The present invention relates to treatment and prevention of nicotine addiction. In particular, the invention relates to novel hapten-carrier conjugates which are capable of inducing the production of antibodies. Such antibodies are capable of specifically binding to nicotine. Furthermore, the present invention envisages preventing or treating nicotine addiction by administering a nicotine-carrier conjugate in a pharmaceutically-acceptable formulation. The present invention also contemplates using the antibodies raised in response to the hapten-carrier conjugate for the prevention and treatment of nicotine addiction. Smoking of cigarettes, cigars, and pipes is a prevalent problem in the United States and worldwide. Smoking tobacco and smokeless tobacco are rich in nicotine, which is a known addictive substance. Nicotine is an alkaloid derived from the tobacco plant that is responsible for smoking's psychoactive and addictive effects. Nicotine is formed of two rings linked together by a single bond: an aromatic six-membered ring (pyridine) and an aliphatic five-membered ring (pyrrolidine). The pyrrolidine is N-methylated and linked through its carbon-2 to the carbon-3 of pyridine. Thus, the carbon-2 is chiral, and there is virtually free rotation around the single bond linking the two rings. It has been established that the absolute configuration of carbon-2 is S. Thus, the natural configuration of nicotine is (S)-(-)nicotine. Nicotine use is widespread due to the easy availability of cigarettes, cigars, pipes and smokeless tobacco. According to the U.S. Department of Health and Human Services, cigarette smoking is the single leading cause of preventable death in the United States. See also McGinnis et al., J. Am. Med. Assoc., 270, 2207-2211 (1993). Exposure to second hand smoke also has been reported to have serious detrimental health effects, including exacerbation of asthma. Web site: http://www.delphion.com/details?pn=US06518031__ •
Inhibition of psychostimulant-induced and nicotine-induced craving Inventor(s): Breiter; Hans C. (Lincoln, MA), Rosen; Bruce R. (Lexington, MA), Marota; John J. A. (Boston, MA), Mandeville; Joseph B. (Somerville, MA), Kosofsky; Barry E. (Swampscott, MA) Assignee(s): The General Hospital Corporation (Boston, MA) Patent Number: 6,517,812 Date filed: September 24, 1998 Abstract: The invention provides methods for inhibiting psychostimulant-induced or nicotine-induced craving of additional psychostimulants (e.g., cocaine or amphetamine) or nicotine. In these methods, D1-like antagonists or D1-like agonists are administered to a patient dependent on psychostimulant drugs or nicotine and therefore susceptible to, or suffering from, such a craving. Also disclosed is an animal model system useful for measuring the ability of test compounds to inhibit pyschostimulant-induced or nicotine-induced cravings in humans. Excerpt(s): This invention relates to inhibition of psychostimulant-induced or nicotineinduced craving in humans. The use of psychostimulants, such as cocaine, and of nicotine often leads to repeated use and a profound state of addiction in humans, which is characterized by compulsive drug use and an inability to control use despite significant adverse consequences. Cocaine, for example, is one of the most reinforcing drugs known (Johanson et al., 1989, Pharmacol. Rev. 41:3-52). Progress toward understanding the neural substrates of addiction to cocaine and other addictive drugs has mostly been limited to research with animal models. The use of such animal models, however, has been limited by the inability to correlate observed patterns of brain
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activation with subjective information about emotional and cognitive responses to drugs, such as euphoria or craving typically experienced after use of addictive drugs. It has now been shown that a distinct pattern of brain activation is exhibited by humans during periods of craving induced by a psychostimulant. As determined by functional magnetic resonance imaging (fMRI), psychostimulant-induced craving (e.g., cocaineinduced craving) is strongly correlated with early, but sustained, signal changes (positive or negative) in the nucleus accumbens and in the amygdala. In contrast, as shown below, the cocaine-induced experience of rush is associated with a pattern of brain activation distinct from the pattern exhibited during cocaine-induced craving. As discussed in further detail below, the studies described herein demonstrate that (a) humans have the same extended neural network of reward circuitry as animals, and (b) this circuitry performs both reinforcement reward and incentive reward function (e.g., craving). These observations, along with (1) observations from animal studies, showing that drugs specific for D1 receptors alter reward processes in the brain and (2) observations regarding the distribution of dopamine receptor subtypes in the brain, indicate that agonists and antagonists of the D1-like receptors can be used to inhibit craving of psychostimulants in humans, with or without inhibition of euphoria. In addition, such agonists and antagonists can be used to inhibit craving of the stimulant nicotine, which is associated with intense craving and is predicted to induce patterns of brain activation that parallel those seen with psychostimulants such as cocaine. Web site: http://www.delphion.com/details?pn=US06517812__ •
Intestinal absorption of nicotine to treat nicotine responsive conditions Inventor(s): Rhodes; John (Cardiff, GB), Evans; Brian K. (Dinas Powis, GB), Rhodes; Peter (Nomansland, GB), Sandborn; William J. (Rochester, MN) Assignee(s): Mayo Foundation for Medical Education and Research (Rochester, MN) Patent Number: 6,238,689 Date filed: April 30, 1999 Abstract: A delayed and sustained release composition of an additive and/or toxic agent such as nicotine is delivered systemically in therapeutic amounts while avoiding the peak plasma levels which gives rise to addiction and/or toxic side effects. The composition is delivered for absorption predominantly from the colon. Excerpt(s): The present invention relates to the use of nicotine composition delivered for absorption from the intestine, particularly the ileum and colon, for the treatment of nicotine responsive conditions particularly schizophrenia, Alzheimer's disease, Tourette's syndrome, Parkinson's disease, depression (particularly associated with cessation of smoking), inflammatory skin conditions, and as an aid to cease smoking. Cigarette smoking has been reported as altering the inflammatory response in the skin following application of irritants and rubefacients (Mills et al, BMJ 1993;307:911). In a follow up study, Mills administered nicotine via a transdermal delivery system and was found to suppress the cutaneous inflammatory response to sodium lauryl sulphate (irritant) and UVB radiation, as well as reactive hyperaemia following arterial occlusion (Workshop on Nicotine as a Therapeutic Agent--May 15, 1996, Frankfurt, Germany). In the same workshop, Sandberg et al reported that administration of nicotine (either 2 mg nicotine gum or 7 mg transdermal nicotine patch) along with neuropleptics produce a decrease in tic symptoms in patients suffering from Tourette's syndrome. A beneficial response of Alzheimer's and Parkinson's disease patients to nicotine was also reported at the workshop. However, nicotine has a substantial effect on the cardiovascular
Patents 393
system including increased heart rate and blood pressure resulting in greater myocardial work and oxygen requirement and coronary vasocontriction. Nicotine has also be purported to activate platelets and to adversely affect blood lipids, thereby promoting atherosclerosis and increasing the risk of acute coronary events. Furthermore nicotine from tobacco products has also been associated with an increased risk of cancer and cerebral haematoma. Web site: http://www.delphion.com/details?pn=US06238689__ •
Low tar and low nicotine cigarette adapted to provide enhanced smoking satisfaction Inventor(s): Rose; Jed E. (Durham, NC), Behm; Frederique M. (Durham, NC) Assignee(s): Duke University (Durham, NC) Patent Number: 5,383,478 Date filed: January 12, 1993 Abstract: A low tar cigarette product and method of use which enhances the sensory impact of low tar and low nicotine cigarettes in order to increase their acceptability and reduce the likelihood that smokers will exhibit compensatory smoking during use thereof. The novel cigarette utilizes an irritant selected from the group consisting of one or more constituents from black and/or red pepper, capsaicinoids, and mixtures of the foregoing in the tobacco thereof. Subsequent to igniting the tobacco and inhaling from the cigarette, the irritant creates respiratory tract sensations in a user substantively similar to those obtained by inhalation of tobacco smoke from a conventional cigarette. Excerpt(s): The present invention relates in general to low tar and low nicotine cigarettes, and more particularly to an improved low tar and low nicotine cigarette which serves to increase the acceptability of low tar and low nicotine cigarettes so as to reduce the harmful effects of cigarette smoking. The most popular brands of conventional cigarettes deliver about 16 milligrams of tar, 1 milligram of nicotine and 16 milligrams of carbon monoxide per cigarette. These potentially harmful substances are believed to account for a considerable number of diseases which have been causally connected to cigarette smoking. This connection between cigarette smoking and health hazards is, of course, well known to the general population today due to efforts by government entities (such as the Office on Smoking and Health of the U.S. Department of Health and Human Services) to educate the general public as to the risks involved in habitual smoking of cigarettes. In recognition of this issue, cigarette manufacturing companies began making and selling a variety of brands of "low tar" cigarettes which deliver relatively small amounts of tar, nicotine and carbon monoxide which could potentially significantly reduce the health hazards associated with smoking cigarettes. Unfortunately, it has been discovered that only a small proportion of the total smoking population (e.g., less than 25%) has substituted low tar cigarettes (e.g., cigarettes that deliver less than 10 milligrams of tar) for conventional and more hazardous cigarettes. Also of note, only about 2.0-3.0% of total cigarette sales are accounted for by very low tar cigarettes (e.g., cigarettes that deliver less than 3 milligrams of tar). Moreover, even among the cigarette smokers who have substituted low tar cigarettes for conventional cigarettes, it has been discovered that these individuals will tend to smoke low tar cigarettes more intensively in order to extract more tar and nicotine than the nominal values listed on the pack. This, of course, defeats part of the objective of the low tar cigarettes. Web site: http://www.delphion.com/details?pn=US05383478__
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Medicated chewing gum delivery system for nicotine Inventor(s): Cherukuri; Subraman R. (Vienna, VA), Pinney; John M. (Bethesda, MD), Henningfield; Jack E. (Baltimore, MD), Sasan; Aradhana (Springfield, VA), Cone; Edward J. (Severna Park, MD), Shiffman; Saul (Pittsburgh, PA), Gitchell; Joe (Chevy Chase, MD), Malvestutto; Carlos D. (Silver Spring, MD) Assignee(s): JSR LLC (Bethesda, MD) Patent Number: 6,344,222 Date filed: September 2, 1999 Abstract: A chewing gum delivery system has nicotine, gum base and a buffer system with an improved release rate for the nicotine. The resulting delivery system advantageously provides a convenient, reliable, practical, and relatively painless system for delivering an active. The delivery system is capable of delivering initial and second doses of a craving reduction active or other actives (e.g., nicotine), the combination of which rapidly reduces cravings, or provides some other pharmacological effect, and provides the pharmacological effect or protection from such cravings over a prolonged period of time beyond the initial dose. Notably, the delivery system is capable of rapidly achieving a pharmacologically effective concentration of the active (e.g., nicotine) in the bloodstream (e.g., within 5 minutes, or more desirably within 3 minutes, or in some cases, within 1-2 minutes), and is also capable of keeping the concentration of the active in the bloodstream at or near the pharmacologically effective concentration for at least 20 minutes after chewing of the delivery system begins, or more desirably about 30 minutes to about 50 minutes after chewing begins. Excerpt(s): The present invention relates to medication delivery systems, and more specifically to nicotine delivery systems, and particularly to a nicotine chewing gum delivery system that provides for an improved nicotine release profile over existing systems. Delivery systems containing actives for oral administration now include various chewing gum formulations. Chewing gums permit release of the active over time as the gum product is masticated, or chewed. The action of saliva on the gum further facilitates release of the active, as well as its subsequent absorption by the mucous membranes lining the mouth, throat, larynx and esophagus. A problem with many chewing gum formulations is that they fail to deliver an adequate dosage of medicament or active in the appropriate manner over the entire dosing interval. This results in insufficient active being absorbed into the bloodstream for effective therapeutic or pharmacological actions. There are many reasons for inadequate dosing. Many chewing gum formulations release active medication slowly over time in a more or less continuous fashion. These formulations may also retain a significant portion of the active during the prescribed dosing period, resulting in inadequate dosing of the patient. Further, the particular gum base material chosen to contain and subsequently release the active material may not perform optimally. The gum base may be difficult to chew or unusually hard, thereby damaging the teeth and gums. The art has not suggested the appropriate gum base formulation, as well as other non-actives, which can be most successfully utilized in combination with a particular type of active. It has therefore proven quite elusive to find the right qualitative and quantitative parameters for both actives and non-actives in the delivery system which will ensure a reliable release rate for the active substance. Web site: http://www.delphion.com/details?pn=US06344222__
Patents 395
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Method and device for transdermally/transbuccally
providing
nicotine
replacement
therapy
Inventor(s): Wong; Ooi (Fremont, CA), Farinas; Kathleen C. (San Francisco, CA), Cleary; Gary W. (Menlo Park, CA), Chiang; Chia-Ming (Foster City, CA), Xia; Jun (Redwood City, CA) Assignee(s): Cygnus Terapeutic Systems (Redwood City, CA) Patent Number: 5,603,947 Date filed: July 21, 1994 Abstract: A skin or buccal patch for providing nicotine replacement therapy which comprises a matrix type laminated composite in which the matrix is composed of a mixture of nicotine in a polymer wherein the amount of nicotine in the matrix, diffusion coefficient of nicotine in the matrix and the thickness of matrix are such that the release of nicotine is: (1) controlled by the patch; (2) rapid and at a relatively high flux over the prescribed wearing time of patch; and (3) such that a substantial proportion of the nicotine initially in the patch has been released at the end of the prescribed wearing time. Excerpt(s): This application relates to transdermal/transbuccal nicotine replacement therapy. More particularly, it relates to a device for and a method of providing transdermal/transbuccal nicotine replacement therapy via a unique dosing regimen which is applicable to heavy smokers. Nicotine replacement therapy is used to provide smokers with nicotine from sources other than cigarettes. It is employed as an aid to assist smokers to quit smoking or to sate smokers who wish to reduce smoking or who are temporarily prevented from smoking for legal and/or social reasons. In nicotine replacement therapy, the nicotine is typically administered parenterally through a body membrane. In the case of administering nicotine via chewing gum, the nicotine is delivered via the mucosal membranes of the oral cavity (i.e., the buccal mucosa). Nasal administration involves transmitting the nicotine to circulation by passage through the nasal mucosa. Finally, in the case of transdermal administration, the nicotine is passed through the skin to the vessels of the circulatory system. Web site: http://www.delphion.com/details?pn=US05603947__ •
Method and product for reducing tar and nicotine in cigarettes Inventor(s): Sung; Michael (1604 Reston Ct., Raleigh, NC 27614) Assignee(s): none reported Patent Number: 6,153,119 Date filed: May 9, 1997 Abstract: A process, and product which uses the process, for reducing tar and nicotine in cigarettes, whereby a novel emulsified complex of Sterotex/permanganate is incorporated into a cigarette. The complex displays a synergistic reaction having a dose response relationship permitting linear adjustment to reduce more than 85% of the tar and nicotine in the mainstream smoke of a cigarette. Chemical analysis of the smoke condensate demonstrates the oxidation of nicotine to nicotinic acid, a B6 vitamin. Excerpt(s): This invention relates to a chemical process, and product which uses the process, for reducing tar and nicotine in cigarettes. The existence of tar and nicotine in cigarette smoke has presented a very serious problem in cigarettes for many years. The
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extent of the health hazards associated with the tar and nicotine have been the focus of many studies and much publicity in recent years. The tar and nicotine in the cigarette smoke is the result of partial combustion. The tar and nicotine exists in both the mainstream smoke, which the smoker draws from the cigarette, and the sidestream smoke, which is commonly known as "second-hand" smoke. Thus, there has been a long-felt need for effective reduction and control of tar and nicotine levels in smoking articles, such as cigarettes, pipes, and cigars. Conventionally, attempts to reduce or control tar and nicotine levels in cigarette smoke have focused on filters which physically remove particulate matter, such as tar and nicotine, from the mainstream smoke condensate, thereby reducing the total particulate matter ("TPM") in the smoke condensate. Thus, the range of cigarettes, from the "full flavor" cigarette to the "light" cigarette to the "ultralight" cigarette, are graded according to the effectiveness of their filters, which can eliminate approximately 50% of the potential tar and nicotine in a normal unfiltered cigarette. Further refinement of filter technology has led to the invention of laser perforated high porosity air dilution filters to further reduce the tar and nicotine in the mainstream smoke. Even these filters, however, fail to reduce the tar and nicotine levels sufficiently and fail to provide adequate control of the tar and nicotine levels. Web site: http://www.delphion.com/details?pn=US06153119__ •
Method for the anhydrous loading of nicotine onto ion exchange resins Inventor(s): Bellamy; Simon Andrew (Redhill, GB), Hughes; Lyn (Harleysville, PA) Assignee(s): Rohm and Haas Company (Philadelphia, PA) Patent Number: 6,607,752 Date filed: June 20, 2001 Abstract: An environmentally friendly method of loading nicotine onto cation exchange resins under anhydrous conditions is described. The method eliminates many of the processing problems that are associated with loading in aqueous media. Excerpt(s): The present invention relates to a method for the loading of nicotine onto cation exchange resins under anhydrous conditions. Nicotine is a naturally occurring alkaloid that is found in the tobacco plant, Nicotiana tobacum. It finds great use in the pharmaceutical and agricultural industries. In the pharmaceutical industry it is extensively used in smoking cessation formulations. In this use the nicotine can be administered in the form of lozenges, chewing gum, and inhalers. When nicotine is formulated into chewing gum and lozenges it is first loaded onto a cation exchange resin which has the effect of controlling the release rate of the nicotine during chewing or sucking in the mouth. Such complexes of nicotine with ion exchange resins are the subject of GB1325011. In agriculture it is used as a pesticide; and it is formulated as the nicotine sulfate salt in water, at a 40% concentration. Web site: http://www.delphion.com/details?pn=US06607752__
Patents 397
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Method for the treatment of nicotine withdrawal syndrome Inventor(s): Hapworth; William E. (250 W. 57th St., New York, NY 10019), Hapworth; Mada S. (250 W. 57th St., New York, NY 10019) Assignee(s): none reported Patent Number: 4,940,585 Date filed: February 17, 1989 Abstract: A therapeutic method for treatment of nicotine withdrawal syndrome symptoms of a patient in need thereof by administering to the patient a therapeutic composition of a pharmaceutically acceptable carrier and fluoxetine in an amount effective to provide physiological relief from the withdrawal symptoms. Excerpt(s): The present invention relates to a method for creating tobacco addiction and in particular to a method in which symptoms of nicotine withdrawal syndrome are relieved, especially the craving for a tobacco product. Jan. 1989 marks the 25th anniversary of the Surgeon General's report linking cigarette smoking to cancer, heart disease, respiratory disease and other conditions. Despite such information being available to the public, a report prepared by the Surgeon General to mark the anniversary concluded that cigarette smoking remains the single most important preventable cause of death in the United States. Benowitz, N. Eng. J. Med. Vol. 319, No. 20, pp. 1318-1330 (Nov. 17, 1988) notes that many people who smoke cigarettes would like to quit but cannot because they are addicted to the psychoactive drug that is the dependence-producing constituent of tobacco, nicotine. Web site: http://www.delphion.com/details?pn=US04940585__
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Method for treating hypertension with nicotine Inventor(s): Hutchinson; Ronald R. (Augusta, MI), Emley; Grace S. (Augusta, MI) Assignee(s): Foundation for Behavioral Research (Augusta, MI) Patent Number: 4,748,181 Date filed: May 15, 1985 Abstract: Hypertension is treated by chronic administration of nicotine or pharmaceutically acceptable salt of nicotine. More specifically, essential hypertension is treated in primates using effective dosages of nicotine. Excerpt(s): This invention relates to a method of treating hypertension which comprises administering to a hypertensive subject requiring such treatment, nicotine or a pharmacologically acceptable acid addition salt of nicotine, for an extended period of time. Nicotine or nicotine related substances have previously been employed or proposed for employment as a treatment for colic (U.S. Pat. No. 101,145), tobacco substitute (U.S. Pat. Nos. 904,521 and 2,981,641), insecticide and parasiticide (U.S. Pat. No. 2,175,980), snake repellent (U.S. Pat. No. 3,069,314), antihistamine potentiator (U.S. Pat. No. 3,126,319), swine food additive (U.S. Pat. No. 3,252,802) and skin care agent (U.S. Pat. No. 2,437,561). U.S. Pat. No. 3,870,794 discloses administering nicotine and related substances to ameliorate emotional disorders, such as anger, hostility, irritability and frustration. Web site: http://www.delphion.com/details?pn=US04748181__
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Method for treating nicotine withdrawal Inventor(s): Rasmussen; Kurt (Fishers, IN) Assignee(s): Eli Lilly and Company (Indianapolis, IN) Patent Number: 5,696,115 Date filed: April 21, 1995 Abstract: The invention provides a method for treating a condition resulting from the cessation and withdrawal of nicotine comprising administering an effective amount of 2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno›2,3-b!›1,5!-benzodiazepine. Excerpt(s): This invention provides a method for using 2-methyl-4-(4-methyl-1piperazinyl)-10H-thieno›2,3-b!›1,5!-benzodiazepine, for the treatment nicotine withdrawal and alleviation of the craving for a tobacco product. Over 25 years ago, the Surgeon General issued a report linking cigarette smoking to cancer, heart disease, respiratory disease and other conditions. Despite such information being available to the public, cigarette smoking remains a significant preventable cause of death in the United States and other developed countries. Benowitz, N. Eng. J. Med. 319:20, 1318-1330 (Nov. 17, 1988) notes that many people who smoke cigarettes would like to quit but cannot because they are addicted to the psychoactive drug that is the dependence-producing constituent of tobacco, nicotine. Web site: http://www.delphion.com/details?pn=US05696115__
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Method for treatment of nicotine craving Inventor(s): Ebbesen; Gerald K. (Dover Rd., South Newfane, VT 05351) Assignee(s): none reported Patent Number: 4,778,677 Date filed: August 15, 1983 Abstract: A method for the treatment of the craving for nicotine in nicotine withdrawal syndrome comprising administering to the patient a composition including glucose or a sugar convertable to glucose in the body of the patient, potassium in ionic form (K+) or a potassium compound capable of dissociating in vivo to release potassium ions, and caffeine or a xanthine equivalent to caffeine in its capacity to elevate the metabolic rate, the glucose and potassium being present in an amount to quickly restore the levels of blood glucose and potassium in the patient to that which his body has become accustomed as a result of repeated nicotine stimulation, caffeine being present in an amount to stimulate metabolism and mental alertness to which his central nervous system has become accustomed by repeated nicotine stimulation. Excerpt(s): This invention relates to the oral administration of a composition of matter having the therapeutic property of alleviating the craving for nicotine that accompanies the nicotine withdrawal syndrome. Therapeutic efforts to break the tobacco smoking habit either through psychological approaches or through the use of various filters or cigarette substitutes have met with varying degrees of sucess. It is generally recognized that bio-feedback from altered physical states can exert an influence on the psyche. The altered physical state induced by tobacco influences the psyche to an extent sufficient to account for a significant measure of its habit forming potential. This physiological component of the cigarette habit can be treated by oral therapy.
Patents 399
Web site: http://www.delphion.com/details?pn=US04778677__ •
Method of administering nicotine transdermally Inventor(s): Osborne; James L. (2365 Thompson Ct., Mountain View, CA 94043), Nelson; Melinda K. (1127 Hollenbeck, Sunnyvale, CA 94087), Enscore; David J. (18291 Montpere Way, Saratoga, CA 95070), Yum; Su I. (1021 Runnymead Ct., Los Altos, CA 94022), Gale; Robert M. (1276 Russell Ave., Los Altos, CA 94022), Causey; Donna D. (1286 Calle Aurora, Camarillo, CA 93010) Assignee(s): none reported Patent Number: 5,633,008 Date filed: August 12, 1993 Abstract: A method of administering nicotine transdermally in which a nicotine patch, capable of administering nicotine for at least 16 hours at rates that are efficacious in smoking cessation therapy, is applied in the morning upon waking and removed prior to sleep. This method is effective even though nicotine is not essential during sleep and many smokers experience morning craving. Excerpt(s): This invention relates to the transdermal administration of nicotine for an extended period of time for smoking cessation. Transdermal devices for the delivery of a wide variety of biologically active agents have been known for some time and representative systems which utilize rate controlling membranes and in-line adhesives are disclosed in U.S. Pat. Nos. 3,598,122; 3,598,123; 3,742,951; 4,031,894, 4,144,317; 4,201,211 and 4,379,454 which are incorporated herein by reference. Such devices generally comprise an impermeable backing, a drug or active agent reservoir and a contact adhesive layer which can be laminated or heat sealed together to produce a transdermal delivery device and an agent release rate controlling membrane is often included between the reservoir and the skin. It has also been proposed to deliver nicotine transdermally to aid in the cessation of smoking, see for example U.S. Pat. Nos. 4,597,961, 4,758,434, and 4,839,174 which are incorporated herein by reference. Web site: http://www.delphion.com/details?pn=US05633008__
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Method of determining the nicotine content of tobacco Inventor(s): Long; Terence M. (Yatton, GB2), Johnson; Joseph C. (Frampton Cotterell, GB2), Naylor; Maurice (Backwell, GB2) Assignee(s): Imperial Tobacco Limited (Bristol, GB2) Patent Number: 4,783,418 Date filed: January 13, 1987 Abstract: A method of determining on a discrete analyzer the nicotine content of tobacco or a smoking-related product by preparing an aqueous extract of a sample of tobacco or smoking-related product, pre-reacting the extract with an acidic buffered solution of pH not more than 6 for at least two minutes, reacting the pre-reacted extract in the discrete analyzer with aniline and cyanogen bromide, measuring the intensity of yellow coloration generated, and comparing said intensity with that produced by a nicotine standard to determine the nicotine content of said sample.
400 Nicotine
Excerpt(s): This invention concerns improvements in or relating to the chemical analysis of tobacco or smoking-related products, in particular for the analysis of nicotine content. In the quality control of cigarettes or other smoking articles it has long been customary to carry out chemical analyses on auto-analyzers of tobacco and other smoking-related products such as filter rod material and cigarette paper. These analyses include analyses for naturally occurring sugars and nicotine in tobacco, glycerol triacetate (triacetin) in cellulose acetate based filter rod material, and citrate salts, which are used as burn modifiers, in cigarette paper. Hitherto, such analyses have been carried out by a number of laboratory technicians, each assigned to a separate analytical task. It is now proposed to carry out simultaneous chemical analyses of tobacco or tobacco-related products for a number of constituents by means of a discrete analyzer (one example of which being the Technicon RA-1000), such as is used in clinical analysis of physiological samples, but adapted to carry out chemical analyses peculiar to the tobacco industry. The use of a discrete analyzer enable analyses to be carried out simultaneously, more effectively, more accurately, and more consistently, on one machine, than can be carried out by a number of separate analytical processes and operators. Web site: http://www.delphion.com/details?pn=US04783418__ •
Method of estimating rate of nicotine metabolism in individuals Inventor(s): Horst; W. Dale (Newton, KS) Assignee(s): Via Christi Research, Inc. (Wichita, KS) Patent Number: 6,472,222 Date filed: February 16, 1999 Abstract: A simple screening method is provided for determining biological variations among individuals in a smoking cessation program so that a therapy regimen can be adjusted appropriately for each individual. The method includes the steps of having an individual intake a predetermined dose of nicotine, taking a saliva sample at a predetermined time subsequent to intake of the dose of nicotine, and measuring the nicotine and cotinine levels in the sample. Thereafter, a ratio is calculated which includes both the nicotine and cotinine levels as an indicator of the rate of nicotine metabolism of the individual being screened. Excerpt(s): The present invention relates generally to smoking cessation methods and, more particularly, to a method for determining biological variations among individuals in a smoking cessation program so that a therapy regimen can be adjusted appropriately for each individual. In the decades since the Surgeon General's report associating smoking with serious diseases and increased death rates, a variety of smoking cessation programs have been employed to help smokers stop smoking. Initially, such programs consisted primarily of behavior modification strategies. Subsequently, nicotine replacement therapy (NRT) was developed in the form of nicotine-containing gum and transdermal patches for use as aids during smoking cessation. Later still, the antidepressant, bupropion was approved for smoking cessation therapy, and was marketed under the trademark ZYBAN.RTM. Over the past decade several programs have been offered which combine behavioral and pharmacological therapies. Smoking a cigarette causes a rapid but short-lived rise in plasma nicotine. Presumably, the trigger to smoke again occurs as one's nicotine level falls sufficiently to produce a "craving" sensation. Thus, the height and duration of the nicotine "spike" has a major impact on smoking frequency, as well as other behaviors such as puff depth and duration, and nicotine content of the preferred brand of cigarette.
Patents 401
Web site: http://www.delphion.com/details?pn=US06472222__ •
Method of loading nicotine into porous polymeric items Inventor(s): Oldham; Ronald G. (San Antonio, TX), Ellis; Michael P. (San Antonio, TX), Hill; Ira D. (Locust, NJ) Assignee(s): Advanced Tobacco Products (San Antonio, TX) Patent Number: 4,736,755 Date filed: January 8, 1986 Abstract: A method of loading nicotine into porous polymeric items consisting essentially of a polyolefin. The method comprises contacting the items with nicotine or nicotine dissolved in a carrier. The polyolefin item, preferably polyethylene or polypropylene, may be loaded with nicotine by several variations on the basic method. The items may be emplaced in a vessel with nicotine and the vessel then closed for a period of time prior to removal of said items.A preferred method of producing porous polyethylene items loaded with nicotine comprises first emplacing porous polyethylene items in a vessel. A solution comprising between about 1% nicotine and about 10% nicotine and a solvent for nicotine demonstrating an adherence for polyethylene surfaces is prepared. A quantity of this solution sufficient to contact at least a majority of the polyethylene items is added to the vessel. Excess solution is then drained from the items and the solvent evaporated from the items to produce porous polyethylene items loaded with nicotine. Excerpt(s): This invention relates to methods of loading porous polyolefinic items with nicotine. These nicotine-loaded porous polyolefinic items are adapted for usage in nicotine dispensers simulating in appearance, for example, cigarettes. The polyolefinic items absorb nicotine in a manner as yet incompletely defined but characterized by a reversibility, i.e., absorbed nicotine may be liberated as a vapor or gas. Previous U.S. patents, for example U.S. Pat. No. 3,280,823, described a tobacco smoke filter comprising nicotine held in ionic bondage to an ion-exchange resin. The use of polyolefins to absorptively and reversibly retain nicotine has not been described except in the copending U.S. patent application Ser. No. 738,120. A method of loading nicotine into porous polymeric items consisting essentially of a polyolefin or polyolefindiene. The method comprises contacting the items with nicotine or nicotine dissolved in a carrier. The polymeric item, preferably consisting essentially of polyethylene or polypropylene, may be loaded with nicotine by several variations on the basic method. The items may, for example, be emplaced in a vessel with nicotine and the vessel then closed for a period of time prior to removal of said items. Web site: http://www.delphion.com/details?pn=US04736755__
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Method of making non-nicotine cigarettes Inventor(s): Liu; Chien-Ching (No. 103, Yi Hua St., Taichung, TW) Assignee(s): none reported Patent Number: 5,150,724 Date filed: March 20, 1991
402 Nicotine
Abstract: The present invention provides a method for making cigarettes with the stems and leaves of fennel and/or foeniculum vulgare in place of tobacco in order to provide a nicotine-free cigarette. Cigarettes made in accordance with this invention minimize the harm to smokers and allow smokers to maintain their health. To produce the cigarettes, fennel and/or foeniculum vulgare may be mixed together or used alone, based on the availability of either plant. The process of making cigarettes from these ingredients is simplified due to differences in the nature and form of the foeniculum vulgare and fennel. The process for making cigarettes of the present invention is simplified and is less costly in comparison to making cigarettes from tobacco. The present invention is beneficial to both smokers and manufacturers. Excerpt(s): The present invention relates to a new type of cigarette filler which does not contain any toxic nicotine. The filler, being made with the stems and leaves of fennel and/or foeniculum vulgare, such as Asiatic foeniculum vulgare, do not contain any toxic nicotine. Cigarettes made in accordance with this invention are not only harmless to habitual smokers, but they are also enjoyable and provide a refreshing feeling. Cigarettes made from tobacco contain nicotine and such cigarettes when lighted and smoked, are deleterious to the health of smokers. The harmful nature of nicotine containing cigarettes is universally known. In fact, it was even known and written about by the ancient Chinese. For example, in the collection of words, book II, it says on page 2,470, "Yen Chien or Yen Tsao Su" is a chemical term for a type of alkaloid. In English it is called nicotine. Nicotine exists in tobacco in formation with malic acid or citric acid. It is a colorless, oily liquid which contains no oxide. It is volatile and water soluble. It smells like tobacco and becomes brown when exposed to air. It is a strong poison; since two or three drops would be fatal for humans. Even a small amount in the lungs causes drowsiness, headache and dizziness. Excessive long term smoking causes clumsiness and stomach and eye disorders. Nicotine has been implicated as a carcinogenic substance by many cancer research organizations throughout the world. For example, in the 1978 and 1982 Journals of the International Agency for Research on Cancer (IARC) it is said that nicotine is a major factor in the cause of cancer. Web site: http://www.delphion.com/details?pn=US05150724__ •
Method of reducing nicotine and tobacco craving in mammals Inventor(s): Coffin; Vicki L. (Basking Ridge, NJ), Glue; Paul W. (Flemington, NJ) Assignee(s): Schering Corporation (Kenilworth, NJ) Patent Number: 6,262,049 Date filed: October 23, 1998 Abstract: A method of reducing cravings in a mammal to nicotine or tobacco is disclosed. The method comprises administering to the mammal an effective amount of a D.sub.1 /D.sub.5 antagonist or a D.sub.1 /D.sub.5 partial agonist alone or in combination with other specified CNS compounds. Excerpt(s): This invention is directed at reducing cravings in mammals. More specifically the present invention is directed at reducing the cravings of a mammal to any dopamine mediated cravings including food or addictive substances. Considerable research has been directed at obesity, nicotine addiction and substance abuse. The cost to society is very high from the health costs associated with obesity, tobacco consumption, and drug and alcohol abuse. While many individuals choose to lose weight, stop smoking and/or cease abusing drugs or alcohol, they frequently relapse
Patents 403
into their former patterns of behavior during or shortly after they complete their treatment programs. Often this may be caused by subtle signals in the environment which initiate cravings in the individual for food or the substance which they had abused. Accordingly, it would be desirable to provide a substance which would suppress cravings for food and/or abused substances in a predisposed mammal. The use of D.sub.1 antagonists in the treatment of drug abuse is known. U.S. Pat. Nos. 4,973,586 and 5,302,716 disclose the use of D.sub.1 antagonists in treating drug dependence. A dosage range of 0.02-10 mg/kg was suggested, with 2.0 mg/kg divided over 1-3 administrations per day being particularly preferred. Web site: http://www.delphion.com/details?pn=US06262049__ •
Method of removing nicotine in smoking and a smoking filter to be used therefor Inventor(s): Minami; Isao (No. 10-3, Aza-kashikiri, Nakamura, Kitajima, Itano, Tokushima, JA) Assignee(s): none reported Patent Number: 3,943,940 Date filed: September 13, 1974 Abstract: This invention relates to a method of removing nicotine in smoking and a smoking filter to be used therefore. The method according to the present invention comprising the impregnation of smoking filter with an aqueous solution of potassium permanganate and chlorine just before smoking and thereby to change, by the smoking filter through which smoke passes, poisonous nicotine contained in the smoke produced from burning of tobacco into nutritious vitamin which is a factor of vitamin B complex. Excerpt(s): In the art of smoking filter, a lot of methods of removing nicotine and smoking filters used for carrying out the methods have been provided conventionally, the methods constituting to remove poisonous substances contained in the smoke produced from burning of tobacco. However, most of the conventional smoking filters are adapted to filtrate only physically the smoke which passes therethrough and remove poisonous substances and they have an inherent defect not to sufficiently remove poisonous substance of nicotine contained in the smoke. A smoking filter is well known in which extremely fine fibers of capillarity and the like having sufficient density are packed in a cylindrical filter case opposite ends of which are opened, in order to filtrate the smoke, however, in this case, the smoking filter filtrates poisonous substances contained in passing smoke only physically so that most of the poisonous substances pass through the smoking filter without removed thereby to affect smokers. In the meantime, it is known that nicotine is dissolved in water. Another smoking filter taking advantages of this feature is also conventionally known in which the nicotine in the smoke produced from burning of tobacco is removed by dissolving the nicotine in the water. In the smoking filter as above-mentioned, a cigar or a cigarette can be insertable to the top end thereof and a water absorbable member is provided in the inside of a filter case having a longitudinal smoke passing aperture therethrough from the top end to the rear end. However, the smoking filter having the above-mentioned construction cannot remove nicotine so efficiently as to be expected because the nicotine once dissolved in the water contained in the smoking filter is evaporated again in the smoke passing through the smoking filter to be mixed therewith and is inhaled into the human body without removed due to extremely high volatile feature of nicotine even in the room temperature. In other words, in the smoking filter containing water, the amount of removing nicotine is estimated at the difference between dissolution amount and
404 Nicotine
evaporation amount of nicotine, however, the evaporation amount of nicotine is so large that the rate of removing nicotine could not be increased. The more cigarettes are used for a smoking filter to remove nicotine, the more nicotine is dissolved in the smoking filter. This results in reducing dissolution volume of nicotine, but, adversely, the evaporation volume of nicotine which is once dissolved in the smoke increased thus reducing conspicuously nicotine removing effect. The present invention comprises to impregnate just before smoking an oxidizing liquid of predetermined concentration in a smoking filter having both features of water absorbability and ventilation, in order to oxidize volatile and deadly poisonous nicotine contained in the smoke produced from burning of tobacco. The oxidizing liquid impregnated in the filter can oxidize a sufficient amount of nicotine contained in the smoke effectively in a short time in which smoke passes through the filter. The oxidizing liquid used for the invention is of a kind and a concentration to be harmless to the human body. The oxidizing liquid is adapted to be impregnated in the smoking filter justs before smoking a cigarette in order to minimize a chemical change of the liquid prior to smoking. Web site: http://www.delphion.com/details?pn=US03943940__ •
Method of treating nicotine dependence Inventor(s): Mason; Barbara J. (Coconut Grove, FL) Assignee(s): The University of Miami (Miami, FL) Patent Number: 5,852,032 Date filed: November 20, 1996 Abstract: A method of treating a subject afflicted with nicotine dependence with the opiate antagonist, nalmefene is described. The subjects will not gain significant amounts of weight as a result of smoking reduction or cessation. Excerpt(s): This application claims the benefit of U.S. Provisional Appln. No. 60/006,962, filed Nov.20, 1995. The invention pertains to methods of treating human subjects suffering from nicotine dependence or addiction. Nicotine dependence accounts for more mortality and morbidity in this country than does dependence on any other substance of abuse, including alcohol, cocaine and heroin. Thus, nicotine dependence represents an enormous cost to the American economy, in terms of health services and lost work days due to illness and premature death. Consequently, the development of safe and effective smoking cessation strategies is an important public health priority. Web site: http://www.delphion.com/details?pn=US05852032__
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Method of using nicotine in the treatment of conditions susceptible to said treatment Inventor(s): Masterson; Joseph G. (Dublin, IE) Assignee(s): Elan Corporation, PLC (Athlone, IE) Patent Number: 5,069,904 Date filed: January 5, 1990 Abstract: A method of using nicotine in the treatment of various conditions susceptible to alleviation by nicotine therapy such as disease states characterized by reduced central cholinergic function. Nicotine is administered to a subject initially having a blood supply substantially free of nicotine at a dose and for a period sufficient to allow the
Patents 405
subject to tolerate the dose and thereafter increasing the dose of nicotine at intervals until a therapeutic dose is achieved. Smokers may also benefit from the treatment regimen. Excerpt(s): This invention relates to a method of using nicotine in the treatment of conditions susceptible to such treatment. Nicotine is the major alkaloid of tobacco and is the most potent alkaloid in tobacco smoke. Nicotine has been shown to act as a primary reinforcer in animals and many of its pharmacological effects are potentially rewarding. It induces tolerances and smokers suffer from physical, as well as, subjective effects when it is withdrawn. Web site: http://www.delphion.com/details?pn=US05069904__ •
Methods and articles of manufacture for nicotine cessation and monitoring nicotine use Inventor(s): Eswara; Amruta R. (Beverly, MA), Muni; Neal (N. Reading, MA), Schneider; F. Howard (Yarmouth, MA), Mione; Peter J. (Abington, MA) Assignee(s): DynaGen, Inc. (Cambridge, MA) Patent Number: 5,780,051 Date filed: January 22, 1997 Abstract: The present invention features methods and articles of manufacture for treating nicotine withdrawal symptoms and promoting smoking cessation. The methods and articles feature the administration of an effective amount of a nicotine substitute and monitor the presence of nicotine in the biological sample of such subject with a nicotine detection system. Excerpt(s): Greater understanding of the adverse health effects of tobacco consumption and associated nicotine intake has led to a marked increase in research on the nature of nicotine addiction and its treatment. Addiction to nicotine, as described in past U.S. Surgeon General's reports on smoking, is widespread, with over 50 million smokers in the United States alone. Addiction to nicotine is a major barrier to an individual's ability to successfully and permanently stop smoking. As with other addictions, addiction to nicotine encompasses two key components. One component is a physiological addiction to nicotine itself. The physiological addiction is mediated through adaptive changes in specific brain nicotine receptors that lead to typical withdrawal symptoms upon abstaining from nicotine. A second component is a complex behavioral component. The behavior component is linked to learned internal cues associated with various positive or negative emotional feelings tied to tobacco smoking or abstinence. The physiological addiction to nicotine is significant. The American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (third edition, revised) lists the officially recognized diagnostic criteria for nicotine withdrawal as the presence of at least four of the following signs: (1) craving for nicotine; (2) irritability, frustration, anger; (3) anxiety; (4) difficulty concentrating; (5) restlessness; (6) decreased heart rate; and (7) increased appetite or weight gain. Web site: http://www.delphion.com/details?pn=US05780051__
406 Nicotine
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Methods and articles of manufacture for the treatment of nicotine withdrawal and as an aid in smoking cessation Inventor(s): Schneider; F. Howard (Yarmouthport, MA), Muni; Indu A. (North Reading, MA), Murty; B. Ram (Lexington, KY), Pandya; Mahendra K. (Massillon, OH), Matharu; Rajinder P. S. (Lexington, KY) Assignee(s): DynaGen, Inc. (Cambridge, MA) Patent Number: 5,414,005 Date filed: October 28, 1993 Abstract: The present application features methods and articles of manufacture for alleviating acute symptoms of nicotine withdrawal and as an aid in smoking cessation. The invention features lobeline held in sublingual tablets for administration to the sublingual and nasal mucosa. Excerpt(s): The present invention features methods and articles of manufacture for the administration of lobeline to humans for the purpose of reducing symptoms of tobacco or nicotine withdrawal and as an aid in smoking cessation. Greater understanding of the adverse health effects of tobacco consumption and associated nicotine intake has led to a marked increase in research on the nature of nicotine addiction and its treatment. Addiction to nicotine, as described in past U.S. Surgeon General's reports on smoking, is widespread, with over 50 million smokers in the United States alone. Addiction to nicotine is a major barrier to an individual's ability to successfully and permanently stop smoking. As with other addictions, addiction to nicotine encompasses two key components. One component is a physiological addiction to nicotine itself. The physiological addiction is mediated through adaptive changes in specific brain nicotine receptors that lead to typical withdrawal symptoms upon abstaining from nicotine. A second component is a complex behavioral component. The behavior component is linked to learned internal cues associated with various positive or negative emotional feelings tied to tobacco smoking or abstinence. Web site: http://www.delphion.com/details?pn=US05414005__
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Methods for nicotine replacement dosage determination Inventor(s): Sachs; David P. L. (3618 Laguna Ave., Palo Alto, CA 94306) Assignee(s): none reported Patent Number: 6,602,892 Date filed: April 13, 1995 Abstract: A method for predicting nicotine replacement dosage to achieve a target nicotine serum concentration relies on measuring blood nicotine concentration prior to smoking cessation. At least two values corresponding to other patient characteristics, such as body mass, cumulative smoking, psychological dependence, age, and menopausal status, are also determined and used to predict expected blood nicotine concentrations based on nicotine replacement dosages. Such methods are useful in achieving target blood nicotine concentrations for smoking cessation and therapy. Excerpt(s): The present invention relates generally to methods for smoking cessation assistance, and more particularly to methods for determining and predicting dosages utilized in nicotine replacement therapy employed in conjunction with smoking cessation techniques. Cigarette smoking is a serious health concern in the United States
Patents 407
and throughout the world, being a significant causative factor in several types of cancer, heart disease, and other disabilities. While the risk of these diseases can be greatly reduced by simply stopping smoking, tobacco dependency makes stopping very difficult for many patients. Thus, there is a continuing need to provide aids for use in smoking cessation therapy. Of particular interest to the present invention, a number of products have been commercially developed for providing nicotine replacement while a patient is undergoing smoking cessation and may suffer the symptoms of nicotine withdrawal. Such nicotine replacement can be achieved by a variety of products, including gums, transdermal patches, nasal spray, inhalers, lozenges, and the like. Frequently, the use of such nicotine replacement products will be combined with physician counseling, group and/or psychological counseling to further increase the chances of long term sustained abstinence. Web site: http://www.delphion.com/details?pn=US06602892__ •
Nasal drug delivery composition containing nicotine Inventor(s): Illum; Lisbeth (The Park, GB) Assignee(s): Danbiosyst UK Limited (Nottingham, GB) Patent Number: 5,935,604 Date filed: July 1, 1996 Abstract: The present invention provides a nasal drug delivery composition comprising nicotine or a pharmacologically-acceptable salt or derivative thereof wherein the composition is adapted to delivery a pulse of nicotine for rapid absorption and a controlled release of nicotine for subsequent sustained absorption. The controlled release phase can be achieved by providing an ion-exchange material which will form a complex with the nicotine. The ion-exchange material may be a polymeric material such as a polysaccharide, or may be in the form of bioadhesive ion-exchange microspheres. The pulse release can be achieved by overloading the ion-exchange material with nicotine so that the composition contains some excess nicotine for immediate release and absorption. Alternatively, some nicotine may be associated with a non ion-exchange material which will release the nicotine immediately on contact with the nasal mucosa, for example non-ion-exchange bioadhesive microspheres. Excerpt(s): The present invention relates to compositions for nasal administration and, more particularly, to compositions for nasal administration of nicotine. Smoking remains the single most important preventable cause of death in modern society. It can be estimated that in the US alone more than 430,000 deaths in 1988 were attributable to cigarette smoking. At least nine out of ten smokers are to some extend dependent upon nicotine and 75% are moderately to strongly dependent and continue smoking despite attempts to stop. In the United States the strong interest in stopping smoking is demonstrated by the fact that nearly 20 million people try to quit smoking each year. Their need for additional help can be seen in the fact that more than 90% fail to maintain their abstinence. The major problem with nicotine is that it is highly addictive. Nicotine fulfils all criteria of an addictive drug, it is psychoactive, it affects the mood, it can act as a primary reinforcer, it induces tolerance, and physical as well as psychological changes occur on withdrawal. Web site: http://www.delphion.com/details?pn=US05935604__
408 Nicotine
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Nicotine addiction treatment Inventor(s): Cary; Douglas D. (Great Falls, VA) Assignee(s): Cary Medical Corporation (Bethesda, MD) Patent Number: 6,197,827 Date filed: November 16, 1999 Abstract: The present invention encompasses methods of treating patients for tobacco addiction and nicotine addiction, for palliating the effects of nicotine withdrawal, for providing or facilitating the effects of smoking cessation therapies and as long-term smoking cessation maintenance therapy. The invention also includes related pharmaceutical compositions comprising nicotine receptor antagonists and either an anti-depressant or an anti-anxiety drug. Specific combinations of drugs (mecamylamine HCl and bupropion HCl) as well as mecamylamine in combination with certain drug classes (e.g., anti-anxiety drugs and anti-depressants) comprise the pharmaceutical compositions disclosed. These compositions are also contemplated for use in the treatment of cocaine addiction and the treatment of alcohol dependence. Excerpt(s): The present invention relates to pharmaceutical compositions and methods of using these compositions to treat patients for tobacco addiction and nicotine addiction, to palliate the effects of nicotine withdrawal and to enhance the outcomes of other smoking cessation therapies. Each agent of the pharmaceutical compositions disclosed has an unique mechanism of action, and when administered concurrently, the combined drugs provide unexpected advantages over existing therapies. Tobacco addiction represents the most important preventable cause of illness and death in our society, responsible for more than 400,000 deaths each year. Currently, one out of five Americans smoke cigarettes, representing almost 50 million smokers in the United States alone. Half of all smokers will die of diseases directly related to tobacco use, and many smokers will suffer significant morbidity. Approximately 15 million smokers try to quit, but only one million of those succeed in smoking cessation each year. A great deal of evidence supports the view that people continue to smoke because of the reinforcing effects of nicotine. Relevant findings include the fact that when allowed to control the nicotine content of each puff, smokers previously deprived of cigarettes, or administered a centrally acting nicotine antagonist, select higher nicotine concentrations. Moreover, under certain conditions, smokers, as well as animals, will self-administer intravenous nicotine. Web site: http://www.delphion.com/details?pn=US06197827__
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Nicotine and/or nicotine metabolite detection Inventor(s): Eswara; Amruta R. (Beverly, MA), Muni; Neal (Reading, MA) Assignee(s): DynaGen, Inc. (Cambridge, MA) Patent Number: 5,707,872 Date filed: June 7, 1995 Abstract: A solid phase capable of detecting the presence of nicotine and/or nicotine metabolites is described. The solid phase is impregnated with assay reagents including a color determinant, a buffer, a cyanogen releasing agent and a cyanogen halide forming agent. The solid phase provides a means whereby unprocessed urine samples over a wide range of different pH values can be tested for the presence of nicotine and/or
Patents 409
nicotine metabolites. The assay results may be determined by direct visualization of the color of the solid phase. Also described are methods of preparing and using the solid phase, and kits containing the solid phase. Excerpt(s): Nicotine use such as by cigarette smoking is a major public health problem. Clinicians and epidemiologists often need an accurate assessment of whether and to what extent a person smokes or otherwise uses nicotine. Relying upon self-reporting by nicotine users regarding their nicotine habits is often inaccurate. In addition, clinicians and epidemiologists may require information concerning inhalation of secondary smoke by non-smokers as well as concerning other passive exposure to nicotine as a result of environmental conditions. Various assays have been developed to independently obtain such information. High performance liquid chromatography (HPLC) has been used to specifically determine the level of cotinine, a nicotine metabolite, in the urine of subjects. (Watson, J. D., J. Chromatogr, 143:203 (1977); Kyerematen, G. A., Clin. Pharmacol. Ther., 32:769 (1982)). Cotinine levels also have been tested using gas chromatography (GC). (Jacob, P. et al., J. Chromatogr. 222:61 (1981); Hengen, N. and Hengert, M., Clin. Chem. 24:50 (1978); Feyerabend, C. and Russell, M., Analyst 105:993 (1980)). Both of these methods require expensive equipment, trained personnel, and are very time consuming. Radioimmunoassays (RIA) (Langone, J., et al., Biochemistry 12:5025 (1973); Knight, G. et al. Clin. Chem. 31:118 (1985)), and enzyme linked immunoassays (ELISA) that measure cotinine have also been developed. (Langone et al. J. Immunol. Methods 114:73 (1988)). Such assays also require special equipment, trained personnel and special reagents. Various assays for isoniazid, a drug used in the treatment of tuberculosis, have been reported. Originally, Rubin et al. (Dis. Chest. 21: 439 (1952)) developed a method for the identification of isoniazid metabolites using cyanogen bromide. Nielsch and Giefer (Arzneimittel-Forschung 9: 636 (1959); Arzneimittel-Forschung 9: 700 (1959)), using chloramine-T and potassium cyanide, developed an assay by which the pyridine ring of isoniazid metabolites is split by cyanogen chloride and condensed with barbituric acid to give a blue to purple color. This was modified by Belle and Littleman (Med. J. Aust. 2: 588 (1962)) for a quantitative determination of isoniazid metabolites, and was later modified by Kasik et al. to be used as a qualitative liquid spot test (Amer. Rev. Resp. Dis. 85: 282 (1962)). Kilburn and Kubica (Amer. J. Clinical Pathology 38: 530 (1968)) modified this test system to enable detection of niacin, utilizing a strip that was impregnated with p-amino salicylic acid, potassium thiocyanate in citric acid and chloramine-T. Subsequently, the reagent impregnated paper strip method was adapted for the detection of isoniazid metabolites. (Kilburn et al., Amer. Rev. Resp. Dis. 106: 923 (1972)). This paper strip system contained barbituric acid, potassium thiocyanate in citric acid, and chloramine-T. Presence of isoniazid metabolites gave a blue to purple color in this assay. Web site: http://www.delphion.com/details?pn=US05707872__ •
Nicotine antagonists for nicotine-responsive neuropsychiatric disorders Inventor(s): Sanberg; Paul R. (Spring Hill, FL), Shytle; Roland D. (Lutz, FL), Silver; Archie A. (Tampa, FL) Assignee(s): University of South Florida (Tampa, FL) Patent Number: 6,034,079 Date filed: November 23, 1998 Abstract: Nicotine-responsive neuropsychiatric disorders can be treated by administering a nicotine antagonist, particularly mecamylamine. Combination therapy
410 Nicotine
of mecamylamine with a neuroleptic drug also is disclosed. The neuropsychiatric disorders include Tourette's syndrome, schizophrenia, depression, bipolar disorder, tremors, attention deficit hyperactivity disorder, obsessive-compulsive disorder, hemidystonia, rage outbursts and tardive dyskinesia. Excerpt(s): The present invention is in the field of pharmacotherapy of nicotineresponsive neuropsychiatric disorders by administering a nicotine antagonist alone, particularly mecamylamine, or in combination with a neuroleptic agent. Examples of such disorders are schizophrenia, bipolar disorder, obsessive compulsive disorder, attention deficit hyperactivity disorder, Tourette's syndrome, and other movement disorders. Tourette's syndrome (TS) is an autosomal dominant neuropsychiatric disorder characterized by a range of symptoms, including multiple motor and phonic tics. It is a hyperkinetic movement disorder expressed largely by sudden, rapid, brief, recurrent, nonrhythmic, stereotyped motor movements (motor tics) or sounds (phonic tics), experienced as irresistible impulses but which can be suppressed for varying lengths of time (Tourette Syndrome Classification Study Group, Arch Neurol 50: 101316). Motor tics generally include eye blinking, head jerking, shoulder shrugging and facial grimacing, while phonic or vocal tics include throat clearing, sniffling, yelping, tongue clicking and coprolalia. The symptoms typically begin in childhood and range from relatively mild to very severe over the course of a patient's lifetime (Robertson M M, Br J Psychiatry, 154:147-169, 1989). Many TS patients also exhibit other neuropsychiatric abnormalities including obsessive compulsive symptoms (Pauls D L et al. Psychopharm Bull, 22:730-733, 1986), hyperactivity and attention deficits (Comings D E, Himes J A, Comings B G, J Clin Psychiatry, 51:463-469, 1990). Problems with extreme temper or aggressive behavior also are frequent (Riddle M A et al. Wiley Series in Child and Adolescent Mental Health, Eds. Cohen D J, Bruun, R D, Leckman J F, New York City, John Wiley and Sons, pp. 151-162, 1988; Stelf M E, Bornstein R A, Hammond L, A survey of Tourette syndrome patients and their families: the 1987 Ohio Tourette Survey, Cincinnati, Ohio Tourette Syndrome Association, 1988), as are school refusal and learning disabilities (Harris D, Silver A A, Learning Disabilities, 6(1):1-7, 1995; Silver A A, Hagin R A, Disorders of Learning Childhood, Noshpitz J D, ed. New York City: Wiley, pp. 469-508, 1990). While the pathogenesis of TS is still unknown, excessive striatal dopamine and/or dopamine receptor hypersensitivity has been proposed (Singer H S et al. Ann Neurol, 12:361-366, 1982), based largely on the therapeutic effectiveness of dopamine receptor antagonists. T S is frequently treated with the dopamine antagonist haloperidol (Haldol.RTM., McNeil Pharmaceutical, Raritan, N.J.), which is effective in about 70% of cases (Erenberg G, Cruse R P, Rothner, A D, Ann Neurol, 22:383-385, 1987; Shapiro A K, Shapiro E, Wiley series in child and adolescent mental health, Eds. Cohen D J, Bruun R D, Leckman J F, New York City, John Wiley and Sons, pp. 267-280, 1988). Other neuroleptics include pimozide (Shapiro E S et al. Arch Gen Psychiatry, 46:722-730, 1989), fluphenazine (Singer H S, Gammon K, Quaskey S. Pediat Neuroscience, 12:71-74, 1985-1986), and risperidone (Stamenkovic et al., Lancet 344:1577-78, 1994). An alternative medication frequently employed is the.alpha.adrenergic agonist clonidine, which also is effective for associated attention deficit hyperactivity disorder (ADHD) but has only a 40% success rate for motor and vocal tics (Bruun R D, J Am Acad Child Psychiatry, 23: 126-133, 1984; Cohen D J et al. Arch Gen Psychiatry 37: 1350-1357, 1980). Other medications that have been used with varying degrees of effectiveness include clonazepam (Gonce M, Barbeau A. Can J Neurol Sci 4:279-283, 1977), naloxone (Davidson P W et al. Appl Res Ment Retardation 4: 1-4, 1983) and fluoxetine (Riddle M A et al. J Am Acad Child Adol Psychiatry 29: 45-48, 1990). One of the most commonly used medications is haloperidol (Erenberg G, Cruse R P, Rothner A D, Ann Neurol, 22:383-385, 1987). However, therapeutic doses of haloperidol have
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frequent side effects that affect compliance, including difficulty in concentration, drowsiness, depression, weight gain, parkinsonian-like symptoms--and with long-term use--tardive dyskinesia (Shapiro A K, Shapiro E, Tourette's syndrome and Tic Disorders: Clinical Understanding and Treatment. Wiley series in child and adolescent mental health. Eds. Cohen, D J, Bruun, R D, Leckman J F, New York City, John Wiley and Sons, pp. 267-298, 1988). The side effect of tardive dyskinesia is particularly bothersome because it may add additional abnormal, involuntary movements of the tongue, jaw, trunk and/or extremities. Web site: http://www.delphion.com/details?pn=US06034079__ •
Nicotine beverage Inventor(s): Thompson; Marshall Anlauf (1253 N. Modesto, Camarillo, CA 93010) Assignee(s): none reported Patent Number: 6,268,386 Date filed: June 25, 1998 Abstract: A liquid composition including a Nicotine or alkaloid having the same direction of activity, content of between 0.0001% and 0.1% that can be consumed orally. Excerpt(s): Tobacco which contains a natural nicotine content has a enormously large and devoted following. This dedication however carries the price of highly accelerated incident of negative health events. While it is the nicotine in tobacco that people seek it is not the nicotine that is the primary cause of negative health events. It is therefore reasoned that if a product could provide nicotine without the other ingredients of tobacco then the risk of negative health events would also diminish. It is insufficient for a safer nicotine product to be available to the public if the form is unacceptable to current tobacco users. Previous nicotine delivery patents have directed their efforts toward mimicking tobacco method of usage or variations of drug application techniques. The goal of this innovation is to introduce the nicotine by a delivery system which is already utilized by all people, the oral consummation of fluids. To be effective however the fluid must be such that is acceptable to its intended users, preferably one or more that are already established. The majority of consumable fluids available to the public have one of these three fluids as their primary ingredients, water, carbonated water or natural juice. Therefore, the objective of this innovation is to form a liquid consisting of nicotine or alkaloid having the same direction of activity with one or any combination of water, carbonated water or natural juice and that the resulting composition could be consumed orally. Said composition may also include one or more ingredients to help make it more appealing to the public. Web site: http://www.delphion.com/details?pn=US06268386__
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Nicotine candy cigarette Inventor(s): Brown; Graham H. (15032 Hanover La., Huntington Beach, CA 92647) Assignee(s): none reported Patent Number: 6,082,368 Date filed: September 9, 1997
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Abstract: A nicotine candy is provided for consumption in small volumes and in a cigarette shaped package. Each portion of the candy is obtained by removing it from a cigarette shaped package from the end. In a first embodiment, standard paper is used to wrap the a series of linearly disposed candy portions. In a second embodiment, the package is made of edible rice paper, and may be torn off of the end in a single piece. The formulation of the candy preferably uses a food grade Beta-pyridyl-alpha-Nmethylpyrrolidine dissolved into any standard hard sugar candy. This material is water soluble and is admixed into the sugar candy composition during candy formation. Preferably, the candy composition is available in a range of strengths which further enables users to regulate their doses. One or two or three pieces can be ingested simultaneously to enable control of the intake, in addition to the availability of the composition in different strengths. Excerpt(s): The present invention relates to the field of chemical and sensory delivery systems, and more particularly to a nicotine candy and packaging which will satisfy both the craving for nicotine as well as the sensory inputs for cigarette consumption, and includes two embodiments for providing a nicotine delivery mechanism. A number of mechanisms are available to assist in smokeless delivery of nicotine to smokers who have acquired the need for such substance in their system. The smokeless nicotine delivery system is needed for a variety of strategies to help smokers deal with a variety of circumstances. For those who need or want to quit, a cessation therapy which involves an alternative delivery system can assist the smoker in tapering off and quitting. Smokers who continue to have the need for nicotine, even where they are unwilling or do not want to quit, need to have nicotine delivery in situations where smoking is unacceptable. There have been external patches for placement on the skin which delivers a timed stream of nicotine in skin permeable form. Side effects of this transdermal delivery approach has included skin irritation, rashes and difficulty in controlling the delivery rate of the nicotine. Web site: http://www.delphion.com/details?pn=US06082368__ •
Nicotine compositions Inventor(s): Spindler; Frank R. (42 Abang Avenue, Tanah Merah, Queensland, 4129, AU), Rawal; Bhupat (Suite 1, Kenmore Village Shopping Centre, Kenmor, QLD, 4069 both of, AU) Assignee(s): none reported Patent Number: 5,326,563 Date filed: September 22, 1992 Abstract: A composition is provided for use in the suppression of a smoking habit, containing a tobacco plant extract which includes between 0.1% and 8.0% of nicotine and at least one additional tobacco derivative in a water based solvent. Excerpt(s): This invention relates to a composition having application in assisting cigarette smokers to abandon their habit. Conventionally, the top leaves of the tobacco plant are harvested at an appropriate time and these are cured and processed for use by smokers. The maturing of leaves, and the temperatures during smoking, generate many different and harmful chemicals. Smoking cigarettes has been linked with lung cancer, cardiovascular diseases, etc. There are many proposals by which those who smoke may he assisted to avoid their habit, hut none are universally effective. It is an object of the present invention to provide a composition which may be utilised by persons who
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require the stimulus that is the motivation for smoking without the risks attendant to smoking. Other objects, and various advantages of the present invention will hereinafter become apparent. Web site: http://www.delphion.com/details?pn=US05326563__ •
Nicotine containing lozenge Inventor(s): Shaw; Alec S. W. (Birch House, Off Crimbles Lane, Cockerham, Lancs, GB2) Assignee(s): none reported Patent Number: 4,967,773 Date filed: June 26, 1987 Abstract: There is disclosed a lozenge formed by compression of at least two mixed components, one of said components including lactose or a lactose containing substance and the other of said components comprising a carrier having nicotine or a nicotine derivative absorbed therein such that there is no direct contact between the nictone and the lactose whilst together in the lozenge. Excerpt(s): This invention concerns a nicotine containing lozenge. Such lozenges are used by smokers either as a substitute for cigarettes or the like in no-smoking areas or as an aid in giving up the smoking habit. One problem with such lozenges is the nausea and discomfort that can follow the ingestion of nicotine or nicotine containing substances. Web site: http://www.delphion.com/details?pn=US04967773__
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Nicotine containing stimulant unit Inventor(s): Dam; Anders (Sollerod Park 16-St. 3, DK-2840 Holte, DK) Assignee(s): none reported Patent Number: 6,110,495 Date filed: November 17, 1997 Abstract: A saliva-soluble stimulant unit comprising an active ingredient and optional ingredients comprising flavor and aroma additives incorporated in a gel prepared by gelling a water-binding gelling agent, in which the active ingredient comprises nicotine or other alkaloids with the same direction of activity, said unit having i) a texture profile, determined by texture profile analysis, with parameter values of firmness, hardness, brittleness, adhesiveness, elasticity, and cohesiveness within given ranges; (ii) a disintegration time within the range 5-60 minutes; and (iii) a nicotine content from 0.5 to 10 mg or a corresponding content of said alkaloids. Excerpt(s): The present invention relates to a saliva-soluble nicotine containing stimulant unit. It is a generally recognized fact that active as well as passive smoking of tobacco products such as pipe tobacco, cigars and cigarettes presents serious hazards to public health as well as to the social environment. It is an equally recognized fact that giving up a smoking habit presents serious problems for a person accustomed to smoking tobacco. Web site: http://www.delphion.com/details?pn=US06110495__
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Nicotine delivery compositions Inventor(s): Blank; Izhak (4 Simtat Arnon, Kiriat Ono 55000, IL) Assignee(s): none reported Patent Number: 6,479,076 Date filed: January 12, 2001 Abstract: A composition containing nicotine and an uncrosslinked, water-insoluble vinylpyrrolidone copolymer is applied on the skin of patients in the form of a gel, ointment, solution, suspension or film which slowly releases nicotine and creates levels of the drug in the blood to reduce nicotine-craving in smokers, thereby assisting in smoking-cessation programs. Excerpt(s): This invention relates to a new method for transdermal nicotine delivery which is particularly useful as a smoking-cessation aid in the treatment of addition to cigarette smoking. Nicotine is the most widely used additive drug. Nicotine is more addictive than heroin, cocaine and alcohol. Every year, 30% of the smokers try to get rid of the habit but only about 3% succeed. In the United States alone there are 50 million smokers, each consuming an average of 10,000 cigarettes a year. This is estimated to cause 420,000 deaths due to lung and heart diseases and cancer. There are at present 1.1 billion smokers in the whole world and the World Health Organization has indicated that by the year 2020 tobacco related illness will be the cause of around 10% of all diseases affecting mankind and will be responsible for 14% of all deaths. The use of tobacco products produces a yearly loss of 200 billion dollars to the economy. In Israel the problem is quite severe. Recent data shows that 28% of adults and 18% of youngsters (below 18 years old) are smokers. It is estimated that every year 10,000 people die due to the smoking habit and another 1,400 die due to passive smoking. Life insurance companies charge approximately double premium payments to smokers as compared to non-smokers. For a one million shekel life insurance policy ($=4 shekel) a 50 year old man will pay 6,690 shekel if he is a smoker and only 3,540 shekel if he is not. Web site: http://www.delphion.com/details?pn=US06479076__
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Nicotine dispenser with polymeric reservoir of nicotine Inventor(s): Ray; Jon P. (12544 Judson Rd., San Antonio, TX 78233), Turner; James E. (307 Wayside, San Antonio, TX 78213), Ellis; Michael P. (811 River Rd., San Antonio, TX 78212), Oldham; Ronald G. (1410 Tarton, San Antonio, TX 78231) Assignee(s): none reported Patent Number: 4,800,903 Date filed: May 24, 1985 Abstract: A nicotine dispenser comprising a polyolefin porous plug with reversibly retained nicotine therein. The dispenser is mounted in a tubular configuration to provide a cigarette-shaped product adapted to dispense nicotine vapor when air is drawn therethrough. The polymeric reservoir of nicotine comprises a polyolefin, preferably polyethylene or polypropylene, which reversibly absorbs nicotine. Excerpt(s): This invention relates to non-combustible nicotine dispensing devices designed to reduce or eliminate the disadvantages associated with conventional
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smoking habits. Nicotine is a toxic liquid alkaloid having the formula C.sub.5 H.sub.4 NC.sub.4 H.sub.7 NCH.sub.3. When nicotine is obtained from tobacco, as by chewing, sniffing or smoking the substance, the amount of nicotine absorbed into the body generally does not build up to a harmful dose, but produces certain pleasurable effects, frequently leading to habitual use. One of the most popular versions of nicotine use involves the smoking of cigarettes. When the tobacco in a conventional cigareete is ignited, the combustion of the processed tobacco leaves within the cigarette causes the release of vaporous nicotine, which is drawn through the cigarette and into the user's mouth and lungs when the user sucks or inhales air through the cigarette. Web site: http://www.delphion.com/details?pn=US04800903__ •
Nicotine dispensing device and method for the manufacture thereof Inventor(s): Ray; J. Philip (2929 Mossrock, Ste. 130, San Antonio, TX 78230) Assignee(s): none reported Patent Number: 4,813,437 Date filed: January 9, 1984 Abstract: An improved nicotine dispensing device for non-pyrolytic use which is adapted to release nicotine-bearing vapors into air drawn through the device. The device comprises one or more nicotine-bearing sections, one or more insulating sections which are linearly aligned with nicotine-bearing sections and a fluid impermeable housing. The housing retains the nicotine-bearing and insulating sections. This invention also includes a method for the preparation of an improved nicotine dispensing device. The method includes the steps of preparing one or more fluid retaining sections and one or more insulating sections. The fluid retaining sections and insulating sections are linearly arranged and wrapped with a fluid impermeable housing material. A nicotine containing material is then injected into, or incorporated within, the fluid retaining sections. Excerpt(s): The use of nicotine has long been practiced by persons in many cultures, who derive satisfaction from the substance. Nicotine is a liquid alkaloid having the formula C.sub.5 H.sub.4 NC.sub.4 H.sub.7 NCH.sub.3 and which is toxic in humans above certain levels. When nicotine is obtained from tobacco, as by chewing, sniffing, or smoking the substance, the amount of nicotine absorbed into the body generally does not build up to a harmful dose, but produces a certain pleasurable effect, frequently leading to habitual use. One of the most popular versions of nicotine use involves the smoking of cigarettes. When the tobacco in a conventional cigarette is ignited, the combustion of the processed tobacco within the cigarette causes the release of vaporous nicotine, which is drawn through the cigarette and into the user's mouth and lungs when the user sucks or inhales air through the cigarette. The relative mildness of a cigarette, as compared to a pipe or cigar, permits a user to draw the smoke from the burning cigarette directly into the lungs. The nicotine vapors in the cigarette smoke are rapidly assimilated into the bloodstream of the user from the lungs, so that cigarette smoking provides a method by which a user may very quickly feel the effects of the nicotine. Preferably to the cigarette user, nicotine is absorbed by the lungs and therefore reaches physiologically significant levels in the bloodstream leading to the brain much more rapidly than if absorbed in the mouth (bucal mucosa) or other tissue. Web site: http://www.delphion.com/details?pn=US04813437__
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Nicotine dispensing device and methods of making the same Inventor(s): Hill; Ira D. (Clay Court, Locust, NJ 07760) Assignee(s): none reported Patent Number: 4,793,366 Date filed: November 12, 1985 Abstract: An improved nicotine dispensing device for non-pyrolytic use which is adapted to release nicotine bearing vapors into air drawn through the device. The device includes a housing and a plurality of microporous polymer filaments which are nicotine loaded. The microporous polymer filaments are characterized by a relatively homogeneous, three-dimensional cellular microstructure. The microporous polymer filaments are made from materials which are selected from olefinic polymers, condensation polymers, oxidation polymers and combinations thereof. Excerpt(s): This invention relates to non-combustible nicotine dispensing devices designed to reduce or eliminate the disadvantages associated with conventional smoking habits. Nicotine is a liquid alkaloid having the empirical formula C.sub.10 H.sub.14 N.sub.2. When nicotine is obtained from tobacco, as by chewing, sniffing or smoking the substance, the amount of nicotine absorbed into the body generally does not build up to a harmful dose, but produces certain pleasurable effects, frequently leading to habitual use. One of the most popular versions of nicotine use involves the smoking of cigarettes. When the tobacco in a conventional cigarette is ignited, the combustion of the processed tobacco leaves within the cigarette causes the release of vaporous nicotine, which is drawn through the cigarette and into the user's mouth and lungs when the user sucks or inhales air through the cigarette. Web site: http://www.delphion.com/details?pn=US04793366__
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Nicotine enhanced smoking device Inventor(s): Ellis; Michael P. (San Antonio, TX), Ray; Jon P. (San Antonio, TX) Assignee(s): Advanced Tobacco Products Inc. (San Antonio, TX) Patent Number: 4,676,259 Date filed: March 21, 1985 Abstract: A nicotine-enhanced smoking article having a first tobacco portion and a second filter portion attached thereto. The filter portion containing filter fibers and a nicotine solution having 5-15%, by weight of total solution, nicotine or a nicotine salt in a solvent. The interaction of the combination products from the first portion with the nicotine solution results in the absorption by the combustion products of nicotine from the solution providing increased nicotine to the user. Excerpt(s): The present invention relates to a nicotine-enhanced smoking device such as a combustible cigarette. The invention also relates to a combustible cigarette enhanced with a nicotine solution which efficiently delivers increased nicotine to the smoker. The invention further relates to a nicotine-enhanced combustible cigarette which delivers increased nicotine to the user without substantially increasing the amount of tar or other combustion products. Tobacco has been used for hundred of years by many cultures throughout the world. Presently, the most popular method is smoking in the form of a cigarette. However, smoking cigarettes is associated with inherent health hazards. Cigarettes low in both tar and nicotine are the result of recent efforts to provide a safer
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cigarette. Medical research has established that nicotine is the active ingredient in tobacco. Small doses of nicotine provide the user with certain pleasurable effects resulting in the desire for additional doses. However, recent medical research published by Russell et al, "Nasal Nicotine Solution, A Potential Aid To Giving Up Smoking?", British Medical Journal, Volume 286 p. 683 (Feb. 26, 1983), indicates that the nicotine itself is not a carcinogen. There is also evidence that nicotine is not responsible for the high rate of premature death among cigarette smokers, for example, see Wald, N. J. et al., Serum Nicotine Levels in Pipe Smokers; Evidence Against Nicotine As Cause of Coronary Heart Disease, The Lancet, Oct. 10, 1981, p. 775. However, one who uses tobacco in the form of conventional cigarettes for the pleasurable effects of nicotine must also risk the dangers of coronary heart disease and cancer that may arise from other components of the smoke which may not contribute to the pleasurable effects that nicotine may produce. Web site: http://www.delphion.com/details?pn=US04676259__ •
Nicotine impact modification Inventor(s): Hill; Ira D. (Locust, NJ) Assignee(s): Advanced Tobacco Products, Inc. (San Antonio, TX) Patent Number: 4,917,120 Date filed: February 7, 1989 Abstract: Compositions comprising nicotine and a volatile nicotine-miscible substance may be used to create sources of modulated nicotine vapor. The modulation of nicotine vapor may be one of quantity or of perceived physiological impact or a combination of both. The substance should have a volatility somewhat similar to that of nicotine and have a normal boiling point between about 175.degree. C. and about 275.degree. C. These compositions may be placed in the nicotine reservoir of a personal oral nicotine inhaler. Esters are preferred nicotine miscible substances, particularly when substantially flavorless and generally recognized as safe for human consumption. Nicotine and nicotine-miscible substance in a weight/weight ratio between about 0.5 and 40.0 are emplaced in a nicotine reservoir, for example absorbed in a porous polyethylene item, for insertion into the tubular passageway of a smokeless cigarette. Excerpt(s): The present invention relates to compositions of nicotine with nicotine impact modification agents and uses of such compositions. Nicotine may be used in the construction of tobacco substitutes. Non-combustible cigarette substitutes, which may be termed "smokeless cigarettes" or "personal oral nicotine inhalers", preferably contain purified nicotine which is dispensed to passing air. Such a smokeless cigarette is described in U.S. Pat. No. 4,284,089, assigned to the assignee of the present invention. 3. the ability to construct mildly-perceived smokeless cigarettes without unacceptably detracting from the self-life of such a product. Web site: http://www.delphion.com/details?pn=US04917120__
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Nicotine in therapeutic angiogenesis and vasculogenesis Inventor(s): Cooke; John (Palo Alto, CA), Jang; James (San Bruno, CA), Tsao; Phillip (San Jose, CA), Heeschen; Christopher (Menlo Park, CA) Assignee(s): The Board of Trustees of the Leland Stanford Jr. University (Palo Alto, CA) Patent Number: 6,417,205 Date filed: July 28, 2000 Abstract: The present invention features methods for induction of angiogenesis by administration of nicotine or other nicotine receptor agonist. Induction of angiogenesis by the methods of the invention can be used in therapeutic angiogenesis in, for example, treatment of ischemic syndromes such as coronary or peripheral arterial disease. Excerpt(s): The invention relates generally to the field of regulation of angiogenesis and vasculogenesis, particularly to induction of angiogenesis to promote growth of new vasculature. Angiogenesis and vasculogenesis are processes involved in the growth of blood vessels. Angiogenesis is the process by which new blood vessels are formed from extant capillaries, while vasculogenesis involves the growth of vessels deriving from endothelial progenitor cells. Angiogenesis and vasculogenesis, and the factors that regulate these processes, are important in embryonic development, inflammation, and wound healing, and also contribute to pathologic conditions such as tumor growth, diabetic retinopathy, rheumatoid arthritis, and chronic inflammatory diseases (see, e.g., U.S. Pat. No. 5,318,957; Yancopoulos et al. (1998) Cell 93:661-4; Folkman et al. (1996) Cell 87;1153-5; and Hanahan et al. (1996) Cell 86:353-64). Both angiogenesis and vasculogenesis involve the proliferation of endothelial cells. Endothelial cells line the walls of blood vessels; capillaries are comprised almost entirely of endothelial cells. The angiogenic process involves not only increased endothelial cell proliferation, but also comprises a cascade of additional events, including protease secretion by endothelial cells, degradation of the basement membrane, migration through the surrounding matrix, proliferation, alignment, differentiation into tube-like structures, and synthesis of a new basement membrane. Vasculogenesis involves recruitment and differentiation of mesenchymal cells into angioblasts, which then differentiation into endothelial cells which then from de novo vessels (see, e.g., Folkman et al. (1996) Cell 87:1153-5). Web site: http://www.delphion.com/details?pn=US06417205__
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Nicotine lozenge Inventor(s): Santus; Gian Carlo (Milan, IT) Assignee(s): Pharmacia AB (Helsingborg, SE) Patent Number: 6,280,761 Date filed: May 15, 1996 Abstract: A method for smoking cessation therapy is described that utilizing an improved nicotine lozenge to satisfy transient craving. The lozenge contains nicotine, a nonnutritive sweetener and an absorbent excipient. Excerpt(s): This invention pertains to compositions and therapeutic methods for reducing the craving for nicotine and for smoking cessation. More particularly, this invention is directed to improved compositions of nicotine lozenges and therapeutic methods to provide periodic doses of nicotine to persons who are attempting to quit smoking. Nicotine replacement therapy as an aid to quitting smoking has been become
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increasingly popular. Nicotine chewing gum (nicotine polacrilex) and transdermal nicotine are two of the more popular forms of nicotine replacement available commercially. It has become clear, however, that the mere replacement of cigarettes with another nicotine source may not be sufficient to insure success in smoking cessation therapy. Specifically, conventional nicotine replacement therapy does not adequately address the symptoms associated with the cessation of smoking. Of the many smoking withdrawal symptoms, craving for cigarettes is one of the most difficult to alleviate. As described in Steuer, J. D. and Wewers, M. E. in Oncology Nursing Forum 1989, 16, 193-198, cigarette craving is one of the most consistent, most severe, and earliest withdrawal symptoms experienced by those attempting to quit smoking. Some reports suggest that craving peaks over the first 24 to 72 hours of abstinence and then declines, although craving has been reported after five years of abstinence. Web site: http://www.delphion.com/details?pn=US06280761__ •
Nicotine lozenge and therapeutic method for smoking cessation Inventor(s): Santus; Gian Carlo (Milan, IT) Assignee(s): Pharmacia AB (Helsingborg, SE) Patent Number: 5,662,920 Date filed: May 15, 1996 Abstract: A method for smoking cessation therapy is described that utilizing an improved nicotine lozenge to satisfy transient craving. The lozenge contains nicotine, a nonnutritive sweetener and an absorbent excipient. Excerpt(s): This invention pertains to compositions and therapeutic methods for reducing the craving for nicotine and for smoking cessation. More particularly, this invention is directed to improved compositions of nicotine lozenges and therapeutic methods to provide periodic doses of nicotine to persons who are attempting to quit smoking. Nicotine replacement therapy as an aid to quitting smoking has been become increasingly popular. Nicotine chewing gum (nicotine polacrilex) and transdermal nicotine are two of the more popular forms of nicotine replacement available commercially. It has become clear, however, that the mere replacement of cigarettes with another nicotine source may not be sufficient to insure success in smoking cessation therapy. Specifically, conventional nicotine replacement therapy does not adequately address the symptoms associated with the cessation of smoking. Of the many smoking withdrawal symptoms, craving for cigarettes is one of the most difficult to alleviate. As described in Steuer, J. D. and Wewers, M. E. in Oncology Nursing Forum 1989, 16, 193-198, cigarette craving is one of the most consistent, most severe, and earliest withdrawal symptoms experienced by those attempting to quit smoking. Some reports suggest that craving peaks over the first 24 to 72 hours of abstinence and then declines, although craving has been reported after five years of abstinence. Web site: http://www.delphion.com/details?pn=US05662920__
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Nicotine metabolites and human body weight Inventor(s): Keenan; Robert M. (2901 Boston St. #209, Baltimore, MD 21224) Assignee(s): none reported Patent Number: 5,869,503 Date filed: May 2, 1994 Abstract: A therapeutic method is provided to alleviate the tobacco withdrawal syndrome, the symptoms of nicotine withdrawal or the management of human body weight in nicotine-experienced or nicotine-naive individuals, comprising of administering an amount of nicotine metabolites or a pharmaceutically acceptable salts thereof to a human in need of such treatment, in an amount which is effective to reduce or eliminate at least one of the symptoms of the tobacco withdrawal syndrome, nicotine withdrawal or manage human body weight. Excerpt(s): The invention relates to the therapeutic methods and articles of manufacture to alleviate the tobacco withdrawal syndrome or manage human body weight with the use of nicotine metabolites or pharmaceutically acceptable salts thereof. The invention includes methods and articles of manufacture using nicotine metabolites or pharmaceutically acceptable salts thereof to alleviate symptoms of nicotine withdrawal and craving associated with cessation of tobacco or nicotine use, as well as the management of human body weight in nicotine-experienced or nicotine-naive humans. Cigarette smoking continues to be the major preventable cause of death in the United States resulting in nearly 400,000 deaths per year due to cancer and cardiovascular disease. Despite the potential adverse health effects, the vast majority of cigarette smokers are unable to cease smoking. The lack of smoking cessation success is thought to be related to the tobacco withdrawal syndrome or tobacco abstinence syndrome that most smokers experience during their attempts to quit. See, Office of Smoking and Health, The Health Consequences of Smoking: Nicotine Addiction. A Report to the Surgeon General, U.S. Govt. Print. Off., Washington D.C., DHHS Pub. No. (CDC) 888406 (1988). The most common effects are similar to those in almost all abstinence syndromes, and include decreased heart rate, anxiety, tension, difficulty concentrating, impatience, depression, increased appetite with accompanied weight gain, irritability and restlessness. See, American Psychiatric Assoc., Diagnostic and Statistical Manual, Washington D.C. (3rd ed. 1980) at pages 159-160, 176-178. Most withdrawal effects occur within 24 hours, peak in the first 1-2 weeks and significantly decrease at one month. It is widely believed that the effects of abstinence from tobacco are due to nicotine deprivation, and that abstinence effects from smoking prevent smokers from stopping. See, J. R. Hughes et al., in Research and Advances in Alcohol and Drug Problems, Vol. 10, L. T. Kozlowski et al., eds., Plenum Pub. Corp. (1990) at pages 317-398. The relationship between tobacco use and decreased body weight has been known for more than 100 years. It has been well established that smokers weigh less than non-smokers. Recent research has shown that nicotine is the substance responsible for the decreased body weight of tobacco users (See, Chapter on Nicotine Dependence, The National Institute On Drug Abuse's Fourth Triennial Report to Congress, In Press). Two major factors related to nicotine use cessation are responsible for weight gain in the posttobacco cessation period including 1) decreased metabolism and/or 2) increased dietary intake. Conversely, it must be the case that nicotine use results in increased metabolism and/or decreased dietary intake. Web site: http://www.delphion.com/details?pn=US05869503__
Patents 421
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Nicotine metabolites and nicotine dependence Inventor(s): Keenan; Robert M. (2901 Boston St. #209, Baltimore, MD 21224) Assignee(s): none reported Patent Number: 5,869,505 Date filed: February 2, 1993 Abstract: A therapeutic method is provided to alleviate the tobacco withdrawal syndrome, the symptoms of nicotine withdrawal or the management of human body weight in nicotine-experienced or nicotine-naive individuals, comprising of administering an amount of nicotine metabolites or a pharmaceutically acceptable salts thereof to a human in need of such treatment, in an amount which is effective to reduce or eliminate at least one of the symptoms of the tobacco withdrawal syndrome, nicotine withdrawal or manage human body weight. Excerpt(s): The invention relates to the therapeutic methods and articles of manufacture to alleviate the tobacco withdrawal syndrome or manage human body weight with the use of nicotine metabolites or pharmaceutically acceptable salts thereof. The invention includes methods and articles of manufacture using nicotine metabolites or pharmaceutically acceptable salts thereof to alleviate symptoms of nicotine withdrawal and craving associated with cessation of tobacco or nicotine use, as well as the management of human body weight in nicotine-experienced or nicotine-naive humans. Cigarette smoking continues to be the major preventable cause of death in the United States resulting in nearly 400,000 deaths per year due to cancer and cardiovascular disease. Despite the potential adverse health effects, the vast majority of cigarette smokers are unable to cease smoking. The lack of smoking cessation success is thought to be related to the tobacco withdrawal syndrome or tobacco abstinence syndrome that most smokers experience during their attempts to quit. See, Office of Smoking and Health, The Health Consequences of Smoking: Nicotine Addiction. A Report to the Surgeon General, U.S. Govt. Print. Off., Washington D.C., DHHS Pub. No. (CDC) 888406 (1988). The most common effects are similar to those in almost all abstinence syndromes, and include decreased heart rate, anxiety, tension, difficulty concentrating, impatience, depression, increased appetite with accompanied weight gain, irritability and restlessness. See, American Psychiatric Assoc., Diagnostic and Statistical Manual, Washington D.C. (3rd ed. 1980) at pages 159-160, 176-178. Most withdrawal effects occur within 24 hours, peak in the first 1-2 weeks and significantly decrease at one month. It is widely believed that the effects of abstinence from tobacco are due to nicotine deprivation, and that abstinence effects from smoking prevent smokers from stopping. See, J. R. Hughes et al., in Research and Advances in Alcohol and Drug Problems, Vol. 10, L. T. Kozlowski et al., eds., Plenum Pub. Corp. (1990) at pages 317-398. The relationship between tobacco use and decreased body weight has been known for more than 100 years. It has been well established that smokers weigh less than non-smokers. Recent research has shown that nicotine is the substance responsible for the decreased body weight of tobacco users (See, Chapter on Nicotine Dependence, The National Institute On Drug Abuse's Fourth Triennial Report to Congress, In Press). Two major factors related to nicotine use cessation are responsible for weight gain in the posttobacco cessation period including 1) decreased metabolism and/or 2) increased dietary intake. Conversely, it must be the case that nicotine use results in increased metabolism and/or decreased dietary intake. Web site: http://www.delphion.com/details?pn=US05869505__
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Nicotine metabolites, nicotine dependence and human body weight Inventor(s): Keenan; Robert M. (2901 Boston St. #209, Baltimore, MD 21224) Assignee(s): none reported Patent Number: 5,573,774 Date filed: June 6, 1995 Abstract: A therapeutic method is provided to alleviate the tobacco withdrawal syndrome, the symptoms of nicotine withdrawal or the management of human body weight in nicotine-experienced or nicotine-naive individuals, comprising of administering an amount of nicotine metabolites or a pharmaceutically acceptable salts thereof to a human in need of such treatment, in an amount which is effective to reduce or eliminate at least one of the symptoms of the tobacco withdrawal syndrome, nicotine withdrawal or manage human body weight. Excerpt(s): The invention relates to the therapeutic methods and articles of manufacture to alleviate the tobacco withdrawal syndrome or manage human body weight with the use of nicotine metabolites or pharmaceutically acceptable salts thereof. The invention includes methods and articles of manufacture using nicotine metabolites or pharmaceutically acceptable salts thereof to alleviate symptoms of nicotine withdrawal and craving associated with cessation of tobacco or nicotine use, as well as the management of human body weight in nicotine-experienced or nicotine-naive humans. Cigarette smoking continues to be the major preventable cause of death in the United States resulting in nearly 400,000 deaths per year due to cancer and cardiovascular disease. Despite the potential adverse health effects, the vast majority of cigarette smokers are unable to cease smoking. The lack of smoking cessation success is thought to be related to the tobacco withdrawal syndrome or tobacco abstinence syndrome that most smokers experience during their attempts to quit. See, Office of Smoking and Health, The Health Consequences of Smoking: Nicotine Addiction. A Report to the Surgeon General, U.S. Govt. Print. Off., Washington D.C., DHHS Pub. No. (CDC) 888406 (1988). The most common effects are similar to those in almost all abstinence syndromes, and include decreased heart rate, anxiety, tension, difficulty concentrating, impatience, depression, increased appetite with accompanied weight gain, irritability and restlessness. See, American Psychiatric Assoc., Diagnostic and Statistical Manual, Washington D.C. (3rd ed. 1980) at pages 159-160, 176-178. Most withdrawal effects occur within 24 hours, peak in the first 1-2 weeks and significantly decrease at one month. It is widely believed that the effects of abstinence from tobacco are due to nicotine deprivation, and that abstinence effects from smoking prevent smokers from stopping. See, J. R. Hughes et al., in Research and Advances in Alcohol and Drug Problems, Vol. 10, L. T. Kozlowski et al., eds., Plenum Pub. Corp. (1990) at pages 317-398. The relationship between tobacco use and decreased body weight has been known for more than 100 years. It has been well established that smokers weigh less than non-smokers. Recent research has shown that nicotine is the substance responsible for the decreased body weight of tobacco users (See, Chapter on Nicotine Dependence, The National Institute On Drug Abuse's Fourth Triennial Report to Congress, In Press). Two major factors related to nicotine use cessation are responsible for weight gain in the posttobacco cessation period including 1) decreased metabolism and/or 2) increased dietary intake. Conversely, it must be the case that nicotine use results in increased metabolism and/or decreased dietary intake. Web site: http://www.delphion.com/details?pn=US05573774__
Patents 423
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Nicotine mucosal spray Inventor(s): Jones; Richard L. (10928-81 Street, Edmonton Alberta, CA T5H 1L5) Assignee(s): none reported Patent Number: 6,596,740 Date filed: October 24, 2001 Abstract: A composition for administration to the nasal mucosa of a subject comprises a solution of nicotine or a pharmaceutically acceptable salt thereof in a pharmaceutically acceptable solvent. The composition has a nicotine concentration less than 10 mg/ml. The composition used alone assists in reduction of the desire of a subject to smoke tobacco. It also reduces the nasal symptoms associated with administration of higher concentrations of nicotine to the nasal mucosa. Excerpt(s): The invention relates to the field of nicotine mucosal sprays, to compositions comprising nicotine that can be administered in a mucosal spray form and to methods and uses therefore. In one embodiment, the invention relates to compositions and methods useful for subjects who wish to reduce tobacco smoking. Due to the reported harmful effects of tobacco smoke and also due to the current social attitudes to smoking, resulting in ever-increasing smoke-free public areas, there is great pressure on tobacco smokers to stop smoking or to find a more socially acceptable alternative. To achieve these goals various forms of nicotine-replacement therapy have been suggested. One such therapy is a nicotine nasal spray (NNS). A commercially available NNS has a nicotine (concentration of 10 mg/ml (Nicotrol NS.RTM., Pharmacia & Upjohn) and is described in U.S. Pat. No. 5,656,255 (the '255 patent). The '255 patent teaches a NNS with a lower limit of nicotine concentration of 10 mg/ml and a preferred concentration of 20 mg/ml (1). Studies using the 10 mg/ml product show that it is an effective aid to quitting smoking (2-9), especially for heavy smokers (2). Recent studies show that, in heavy smokers who successfully quit smoking while using 10 mg/ml NNS, venous plasma nicotine levels were approximately two-thirds the level seen while smoking (9). Therefore, 10 mg/ml NNS is an effective nicotine replacement therapy in which plasma nicotine levels reach the range where most of the nicotine withdrawal symptoms are avoided (10, 11). Studies leading to the '255 patent suggested that a nicotine concentration of 10 mg/ml was the lower limit capable of delivering sufficient nicotine to the blood plasma (2/3 of nicotine level seen while smoking) to avoid withdrawal symptoms. Web site: http://www.delphion.com/details?pn=US06596740__
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Nicotine oral delivery device Inventor(s): Gross; Joseph (Dublin, IE), Kelly; John Gerard (Dublin, IE) Assignee(s): Elan Medical Technologies Limited (Athlone, IE) Patent Number: 5,799,663 Date filed: December 23, 1996 Abstract: A nicotine oral delivery device, which includes a hollow housing (10) and a hollow mouthpiece (14) which may be detachable connected to the housing (10) or may form with the housing a single piece. The mouthpiece includes a nicotine-containing material (16), in the form of a gel, on one or more of the outer surfaces of the mouthpiece. The housing (10) may also include flavoring (20), such as menthol. The
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nicotine-containing material (16) may be located as a layer on the mouthpiece (14), or in holes in the mouthpiece or under a permeable membrane (18) covering a portion of the mouthpiece (14). Where the mouthpiece and housing are separate pieces, the mouthpiece may be disposable while the housing reusable. Excerpt(s): The present invention relates to means for aiding in the breaking of the cigarette smoking habit and, more particularly, to a device for the oral delivery of nicotine. It has been amply established that cigarette smoking is addictive in at least two respects. First, the typical cigarette smoker is chemically addicted to the nicotine contained in the cigarette. In addition, most smokers are also physically addicted to the cigarette as an object of stimulation and manipulation by the lips, and to some extent, the hands. There is overwhelming evidence linking cigarette smoking to cancer, most significantly, to lung cancer which is believed to be initiated and stimulated by the repeated contact of cigarette smoke with sensitive lung tissue. Web site: http://www.delphion.com/details?pn=US05799663__ •
Nicotine packaging materials Inventor(s): Hunt; James A. (Fremont, CA), Osborne; James L. (Mountain View, CA), Dunn; John T. (Redwood City, CA), Nelson; Melinda K. (Sunnyvale, CA), Roth; Nathan (San Francisco, CA) Assignee(s): Alza Corporation (Palo Alto, CA) Patent Number: 5,268,209 Date filed: October 21, 1991 Abstract: The invention herein pertains to methods and materials for producing a nicotine maintenance pouch. Laminates comprising a nicotine barrier layer and a nicotine degradation agent barrier layer are disclosed. In a preferred embodiment, the nicotine barrier layer comprises a nitrile rubber modified acrylonitrilemethyl acrylate copolymer. An especially preferred nicotine barrier material comprises, by weight percent, 75% acrylonitrile, and 25% methyl acrylate with 10% butadiene (AN-MA/B). The nicotine degradation agent barrier layer is preferably aluminum foil. In an especially preferred embodiment, the laminate comprises a layer of AN-MA/B adhered to a layer of aluminum foil, which in turn is adhered to a layer of paper stock.Pouches comprising a self-sealed nicotine barrier layer and a nicotine degradation agent barrier layer are disclosed. These pouches are preferably formed from the laminates above.A method for production of pouches comprises: (a) providing a laminate including a selfsealable nicotine barrier layer and a nicotine degradation agent barrier layer; and (b) sealing the self-sealable nicotine barrier layer to enclose a nicotine device. Excerpt(s): The invention herein pertains to materials and methods for the manufacture of nicotine storage pouches. Nicotine base is a reactive species which decomposes in the presence of oxygen or light. It is highly hygroscopic. Nicotine base causes the solvation of standard adhesives, which cannot be effectively used to seal nicotine-containing pouches. The problem of providing containment for consumer products containing nicotine base has heretofore found no simple solution. A transdermal system for the delivery of nicotine is disclosed in Australian Patent Application Au-A-81454/87. In that system two nicotine precursors are sealed in burstable pouches. Only after application to skin and rupture of the pouches is the highly reactive nicotine base formed. Web site: http://www.delphion.com/details?pn=US05268209__
Patents 425
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Nicotine removal process Inventor(s): Casey; William J. (Trumbull, CT) Assignee(s): AMF Incorporated (White Plains, NY) Patent Number: 4,068,671 Date filed: July 25, 1975 Abstract: This invention concerns a method of removing nicotine from tobacco by rapid drying of an alkaline aqueous dispersion of tobacco. Preferably, the dried tobacco is remoistened with water and subsequently rapidly re-dried to realize higher efficiency of nicotine removal. Excerpt(s): This invention relates to a method of removing nicotine from tobacco. Nicotine is an alkaloid which is physiologically active in human hosts and the nicotine of cigarette smoke has been associated with cardiovascular disturbances in cigarette smokers (see: The Health Consequences of Smoking, A Public Health Service Review: 1967). A number of methods for removing nicotine from tobacco are known, most of these relying on extraction procedures using solvents, including reactive solventsystems. The most common solvent systems employ water as at least a component, and usually include a basic material to neutralize the nicotine acid salts thus liberating the free base which is soluble in a variety of solvents. In this latter regard, U.S. Pat. No. 2,822,306 describes the removal of nicotine from tobacco by solvent extraction as by the Soxhlet method, or by leaching with large volumes of water, containing basic materials to neutralize the nicotine acid salts contained in natural tobacco, i.e. phosphoric acid salts. As pointed out in the said patent, and as is inherent in any of the solvent extraction or water-leaching methods of removal of nicotine, a considerable amount of tobacco solubles other than nicotine is also removed from the tobacco. These solubles have to be returned to the tobacco in order to preserve the original tobacco taste characteristics, and are so returned after solvent extraction of nicotine from the original extract and after concentration of the extract. Web site: http://www.delphion.com/details?pn=US04068671__
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Nicotine removal process and product produced thereby Inventor(s): Lenkey; Attila A. (Short Hills, NY) Assignee(s): Helme Tobacco Company (Stamford, CT) Patent Number: 4,848,373 Date filed: April 13, 1987 Abstract: A process for removing nicotine from tobacco which does not adversely affect the flavor and aroma of the product tobacco is disclosed. The process entails mixing a tobacco having a moisture content of 25% to 53% with an alkalinizing agent to obtain a pH of 8 to 11 and maintaining the tobacco in an aerobic environment at a temperature of 40.degree. F. to 120.degree. F. at a pressure of 1 atmosphere for a period of 4 to 14 weeks. The product so produced is also disclosed. Excerpt(s): The present invention relates to tobacco and more particularly to a process for preparing a low nicotine, smokeless tobacco product having good flavor and aroma. This process is especially suited for moist snuff. Smokeless tobacco products, such as
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moist snuff and chewing tobacco, are enjoyed by inserting the smokeless tobacco product between the gum and the lip or cheek and extracting the solubles from the product with saliva. Flavor and aroma are especially important in smokeless tobacco products because of the direct contact between the product and the user's taste buds. Known methods for reducing the nicotine content of tobacco involve the removal of the nicotine from tobacco by subjecting the tobacco to extreme conditions which remove other solubles along with nicotine and adversely effect the flavor and aroma properties of the smokeless tobacco product. For example, it has been suggested that nicotine be removed from tobacco by: spray drying tobacco in an alkaline environment, see U.S. Pat. No. 4,068,671; microbial treatment of tobacco, see U.S. Pat. Nos. 4,011,141 and 4,038,993; using a donor tobacco at 140.degree. F. to receive the nicotine from the tobacco, see U.S. Pat. No. 4,215,706; using a gas or liquid at high pressure or temperature, see U.S. Pat. Nos. 4,289,147 and 2,822,306. These methods are drastic and call for extreme conditions which have a deleterious effect on the flavor and aroma of smokeless tobacco product made from tobacco product of these processes. Web site: http://www.delphion.com/details?pn=US04848373__ •
Nicotine therapy method and oral carrier for assuaging tobacco-addiction Inventor(s): Smith; Steve (5100 Channel Ave., Richmond, CA 94804), Wilhelmsen; Paul C. (281 Livorna Heights, Alamo, CA 94507) Assignee(s): none reported Patent Number: 6,583,160 Date filed: August 23, 2001 Abstract: A method for assuaging tobacco addiction comprises pulsing doses of nicotine into a user's bloodstream so it reaches the brain before passing through the liver. A nicotine-burst tablet is held in the mouth by a user to receive each nicotine-pulse dose. The tablet is configured to suddenly release its entire nicotine payload from an otherwise inert or benign material. Such nicotine payload is relatively small, e.g., under one milligram. The therapeutic effects depend on the change of nicotine levels in the blood over a change in time. Rapid nicotine onset of a small dose is more assuaging than a slow build-up to a high dosage. An oral carrier comprises a nicotine saturated instantdissolve paper that delivers one nicotine pulse. An additive prevents abuse by causing excessive use to catalyze a foul taste or sickening sensation. Excerpt(s): The present invention relates to tobacco-addiction therapies, and more particularly to methods and devices for assuaging nicotine cravings in users. Tobaccoaddiction is a serious health problem through out the world. The hundreds of compounds carried along with the nicotine cause most of the trouble, but the nicotine is responsible for the chemical addiction. Tobacco users find it too difficult to quit because both the nicotine cravings and ritual behaviors are too severe and ingrained. The prior art has therefore developed a multitude of therapies, devices, and methods for helping people quit tobacco. Many of them follow similar ritual patterns of putting things in the mouth. Given the large number of users who continue using tobacco, it can be assumed that no prior art attempt has been completely successful. Web site: http://www.delphion.com/details?pn=US06583160__
Patents 427
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Nicotine transfer process Inventor(s): Larson; Thomas M. (McLeansville, NC), Moring; Thomas B. (Jamestown, NC), Ireland; M. Sue (Greensboro, NC) Assignee(s): Loew's Theatres, Inc. (New York, NY) Patent Number: 4,215,706 Date filed: October 13, 1978 Abstract: Tobacco (donor tobacco) is contacted with a receiving substrate which has been treated with a strong acid or an ammonium salt of a strong acid. Part of the nicotine in the donor tobacco is transferred from the donor tobacco to the receiving substrate. Thereafter the donor tobacco and the substrate may be separated. The donor tobacco has a reduced nicotine content and hence more desirable for use in a smoking product. Where the receiving substrate is a low nicotine tobacco by-product (or artificial smoking material) said substrate, enriched in nicotine as a result of the transfer, may be used as a filler material for smoking products. Excerpt(s): The present invention relates to a novel and highly efficient nicotine transfer process, and, more particularly, to a process for transferring nicotine from a tobacco source to a nicotine deficient tobacco, a tobacco filler material, reconstituted tobacco (referred to as "reconstituted leaf" or "RL") or to a non-tobacco substance. The flavor of tobacco, RL or the like to which naturally occurring nicotine is transferred by the process, is usually improved and the receiving material is thus more desirable for use in a tobacco product. The nicotine source tobacco (from which nicotine is transferred) may, because of a lowered nicotine content, also be improved and more useful. The transfer process of the present invention is also useful outside the tobacco industry in that the nicotine-receiving material can be used as a nicotine source for various purposes unrelated to tobacco products. Various techniques are known for producing nicotine free tobacco or a tobacco having a reduced nicotine content. Denicotinizing processes frequently employed are based either on the principle of direct solvent extraction of nicotine compounds whereby soluble compounds are washed out, or on the principle of leaching the tobacco with an alkaline aqueous solution which depends upon a chemical reaction to break down insoluble compounds which thereafter are washed out. Most, if not all of these prior art techniques, however, suffer from the fact that they significantly rob the treated tobacco of properties generally identified with a quality smoking product. The process of the present invention offers a significant advance in tobacco technology by, for one thing, providing a simple, economical and effective process for reducing the nicotine content of tobacco without the usual accompanying degredation of the physical properties of the tobacco or smoke, such as the flavor, fragrance or burning qualities. Moreover, the process is useful for transferring naturally occurring nicotine from tobacco having a generally high nicotine content to a nicotine deficient tobacco, tobacco filler materials, or RL (reconstituted leaf) which are used in the production of cigarettes and other smoking products. It should be noted however that a low nicotine tobacco having properties which make it generally unusable can also be used as the nicotine donor in the present process. Web site: http://www.delphion.com/details?pn=US04215706__
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Nicotine-containing dental floss Inventor(s): Mondre; Steven J. (370 E76 B1501, New York, NY 10021) Assignee(s): none reported Patent Number: 5,035,252 Date filed: December 14, 1990 Abstract: Nicotine treated dental floss is disclosed which is useful in alleviating tobacco smokers' urges to smoke. Excerpt(s): The present invention relates to dental floss. More particularly, the present invention relates to dental floss treated with nicotine and preferably to nicotinecontaining dental floss. Most particularly, the present invention relates to a novel dental floss combination, and related method, for alleviating the urge to smoke tobacco while at the same time providing for the beneficial effects resulting from frequent dental flossing. Many persons who have acquired the habit of smoking tobacco are desirous of quitting. However, the addicting effects of tobacco smoking make it difficult for smokers to quit. Further, tobacco smoke is known to have deleterious effects to a person's teeth, gums and periodontal areas such as discoloration and gingivitis. The health hazards from tobacco smoking are well established. Of the approximately 4,000 by-products of combustion found in cigarette smoke, many of which are known carcinogens, the three substances studied most have been tars, carbon monoxide and nicotine. Tars and carbon monoxide have been directly implicated in the production or exacerbation of numerous health disorders. Web site: http://www.delphion.com/details?pn=US05035252__
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Nicotine-containing, controlled release composition and method Inventor(s): Walling; John Allen (Union Grove, WI) Assignee(s): Cambrex Charles City, Inc. (Charles City, IA) Patent Number: 6,586,449 Date filed: May 28, 2002 Abstract: A nicotine product having a nicotine release rate of not less than 70% over a 10 minute period as well as a process to produce such product Such product is produced by a process comprising the steps of(a) preparing an aqueous solution of an organic polyol;(b) mixing said aqueous solution of the organic polyol with a cation exchange resin selected from the group consisting of (i)--a methacrylic, weakly acidic type of resin containing carboxylic functional groups (ii)--polystyrene, strongly acidic type of resin containing sulfonic functional groups and (iii)--polystyrene, intermediate acidic type of resin containing phosphonic functional groups thereby forming a cation exchange resin mixture having some of its ion exchange sites partially blocked with said polyol;(c) admixing with said mixture of step (b) an aqueous solution of nicotine to form a nicotine-coated cation exchange resin admixture; and(d) removing water from said admixture. The nicotine composition having a nicotine release rate of not less than 70% over a 10 minute period results. Excerpt(s): This invention relates to a method for producing a nicotine-containing composition having a controlled release rate of nicotine. More particularly, this invention relates to a process for producing product comprising nicotine and a cation exchange resin, such product having a nicotine release rate of at least 70% over a 10
Patents 429
minute period. Nicotine is a well know, highly characterized alkaloid that can be isolated from the dried leaves of Nicotiana tabacum. Its numerous commercial uses include utilities such as a fimnigant, an insecticide and the like. It is therapeutically valuable in the treatment of the smoking withdrawal syndrome. This treatment is based on the fact that the administration of nicotine into the body has been readily accomplished by the method of smoking, e.g., from cigarettes, pipes or cigars. The smoker experiences a satisfactory sensation from such administration. However, smoking may be associated with health hazards not necessarily associated with nicotine administration itself. As a result, non-smoking methods have been devised to administer nicotine to the body. These include nicotine-containing chewing gums, nicotine-impregnated dermal patches, nicotine inhalers and the like. A variety of patents have disclosed such products. Web site: http://www.delphion.com/details?pn=US06586449__ •
Nicotine-impermeable container and method of fabricating the same Inventor(s): Turner; James E. (Atascosa, TX), Ellis; Michael P. (San Antonio, TX), Oldham; Ronald G. (San Antonio, TX), Hill; Ira (Locust, NJ), Malmborg; Bengt E. (Helsingborg, SE), Andersson; Sven-Borje (Od.ang.kra, SE) Assignee(s): Pharmacia Biosystems Aktiebolag (SE) Patent Number: 5,400,808 Date filed: November 25, 1992 Abstract: The present invention relates to a nicotine-impermeable container including a barrier layer of acrylonitrile and methyl acrylate and a method for fabricating same. Additionally, the invention relates to a nicotine inhaling device which allows a user to ingest nicotine vapors orally. The nicotine inhaling device of the present invention is primarily directed to a device which can be used as a smoking cessation aid. Excerpt(s): The present invention relates to a nicotine-impermeable container and a method for fabricating same. A preferred embodiment of the invention is a nicotine inhaling device which allows a user to ingest nicotine vapors orally and is primarily used as a smoking cessation aid. Evidence has been mounting over the years linking many diseases such as high blood pressure and lung cancer to cigarette smoking. The U.S. Surgeon General's report of 1988 on the health consequences of smoking estimated that in the United States alone about 300,000 deaths are caused each year by cigaretterelated diseases. Indeed, excessive smoking is now recognized as one of the major health problems throughout the world. Because of the addictive nature of nicotine, it is extremely difficult for a heavy smoker to stop smoking completely. Even though nicotine is one of the risk factors in tobacco smoke, other substances formed during the combustion of tobacco such as carbon monoxide, tar products, aldehydes and hydrocyanic acid are considered to be even greater risk factors. Web site: http://www.delphion.com/details?pn=US05400808__
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Nicotine-impermeable container and method of fabricating the same Inventor(s): Turner; James E. (Atascosa, TX), Ellis; Michael P. (San Antonio, TX), Oldham; Ronald G. (San Antonio, TX), Hill; Ira (Locust, NJ), Malmborg; Bengt Eber (Helsingborg, SE), Andersson; Sven-Borje (Od.ang.kra, SE) Assignee(s): Pharmacia & Upjohn AB (SE) Patent Number: 6,098,632 Date filed: February 20, 1997 Abstract: The present invention relates to a nicotine-impermeable container and a method for fabricating same. Additionally, the invention relates to a nicotine inhaling device which allows a user to ingest nicotine vapors orally. The nicotine inhaling device of the present invention is primarily directed to a device which can be used as a smoking cessation aid. Excerpt(s): The present invention relates to a nicotine-impermeable container and a method for fabricating same. A preferred embodiment of the invention is a nicotine inhaling device which allows a user to ingest nicotine vapors orally and is primarily used as a smoking cessation aid. Evidence has been mounting over the years linking many diseases such as high blood pressure and lung cancer to cigarette smoking. The U.S. Surgeon General's report of 1988 on the health consequences of smoking estimated that in the United States alone about 300,000 deaths are caused each year by cigaretterelated diseases. Indeed, excessive smoking is now recognized as one of the major health problems throughout the world. Because of the addictive nature of nicotine, it is extremely difficult for a heavy smoker to stop smoking completely. Even though nicotine is one of the risk factors in tobacco smoke, other substances formed during the combustion of tobacco such as carbon monoxide, tar products, aldehydes and hydrocyanic acid are considered to be even greater risk factors. Web site: http://www.delphion.com/details?pn=US06098632__
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Non-combustible anti-smoking device with nicotine impregnated mouthpiece Inventor(s): Edwards; Patrica T. (P.O. Box 61194, San Angelo, TX 76906) Assignee(s): none reported Patent Number: 5,293,883 Date filed: May 4, 1992 Abstract: The invention includes a non-pyrolytic cigarette, having an elongated tube of approximately the same, shape, dimensions, and weight of a traditional cigarette. The elongated tube contains two tobacco-filled chambers along its length and incorporates a filter at the end placed in the mouth of the user. The chambers contain pre-burned tobacco and unburned tobacco. A central air passageway communicates with the tobacco-containing chambers, and provides the taste, smell and sensation of a traditional cigarette as air is drawn through the tube and is delivered to the user. Additionally, a multiplicity of nicotine-containing ampules located within the mouth filter release liquid nicotine into the mouth of the user when pressure is applied to the filter. Excerpt(s): This invention relates to smoking devices and, more particularly, to a smokeless cigarette which provides the look, feel and taste of a traditional cigarette without the ignition and combustion of tobacco. The most popular use of nicotine, an
Patents 431
addictive, relatively harmless agent produced from the combustion of tobacco, involves the smoking of cigarettes or cigars. Individuals inhale the smoke from these devices in an effort to obtain the pleasant physiological effect that nicotine has on the body. Nicotine is absorbed by the lungs when the smoker inhales the smoke. Unfortunately, nicotine is only one of over four thousand components of cigarette smoke, four hundred of which are known carcinogens or harmful toxins. It is now widely known that these other elements of cigarette smoke are responsible for a number of serious physical ailments, including lung cancer. Additionally, recent studies indicate that even secondhand smoke (i.e., smoke inhaled while in close proximity to a smoker) can cause these same maladies in non-smokers. Furthermore, a substantial number of fires are caused as a result of smoking. Thousands of people are injured or killed, and millions of dollars in property loss occur each year in the United States as a direct result of cigarette smoking. Finally, a few relatively minor problems associated with smoking--stained teeth, dry and wrinkle-prone skin, and smoke-damaged clothing--make the habit annoying as well as dangerous. Web site: http://www.delphion.com/details?pn=US05293883__ •
Non-nicotine smoking cessation aid Inventor(s): Rose; Jed E. (Durham, NC), Behm; Frederique M. (Durham, NC) Assignee(s): Duke University (Durham, NC) Patent Number: 5,893,371 Date filed: September 21, 1994 Abstract: A non-nicotine method and apparatus for use to reduce the need to smoke tobacco and which utilizes one or more constituents from black pepper or red pepper which are introduced into the user's respiratory tract by inhalation from either a vapor delivery system or an aerosol delivery system. Subsequent to inhalation, the constituents from black pepper or red pepper create respiratory tract sensations similar to those created by tobacco smoke and thereby serve to reduce the need to smoke tobacco. The one or more constituents from black and/or red pepper include essential oils of black and/or red pepper as well as pepper irritants including capsaicin, piperine and phellandrene. Excerpt(s): The present invention relates in general to a smoking cessation aid, and more particularly to a non-nicotine smoking cessation aid which uses one or more constituents from black and/or red pepper to simulate sensations in the respiratory tract which would normally be caused by tobacco smoke in order to reduce the need of the user to smoke tobacco. With the increasing recognition of the health hazards associated with cigarette smoking, increasing attention has been focused on less harmful means to provide some of the same satisfaction obtained by smoking. Some of the methods rely on nicotine replacement through nicotine chewing gum, nicotine skin patches or nicotine nasal sprays. Research conducted over the last 12 years by applicants has explored the role of nicotine as a reinforcer for smoking and has investigated the efficacy of nicotine replacement as an aid to smoking cessation. While it is clear from applicants' work and that of others that nicotine replacement can facilitate smoking cessation by providing some relief for certain withdrawal symptoms, such as irritability and difficulty concentrating, it is equally clear that subjective craving for cigarettes is not effectively relieved by the pharmacologic effects of nicotine alone. An analogy can be drawn to hunger and food consumption, in which intravenous or intragastric feeding is not nearly as satisfying as eating a meal.
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Web site: http://www.delphion.com/details?pn=US05893371__ •
Novel transdermal nicotine patch Inventor(s): Baker; Richard W. (Palo Alto, CA), Kochinke; Frank (Mt. View, CA), Huang; Carl (Palo Alto, CA) Assignee(s): Pharmetrix Corporation (Menlo Park, CA) Patent Number: 4,839,174 Date filed: October 5, 1987 Abstract: A controlled release transdermal delivery system for nicotine administration. The system comprises an impermeable backing layer, a polyurethane matrix layer containing between about 5 wt % and 50 wt % nicotine, and an adhesive skin-contacting layer. The system is designed to administer nicotine for smoking cessation therapy or other uses over a period of 24 hours or more. Excerpt(s): The invention relates to a controlled release transdermal delivery system for administering nicotine. Delivery of drugs by the transdermal route has been known to be theoretically possible for many years. The earliest patented transdermal devices were medicated bandages, usually with the drug mixed into the adhesive, that were designed to bring a known quantity of drug to a known area of skin for a known time. Such devices usually did not control the rate at which the drug was released. Since the 1970's interest in using the transdermal route for controlled release therapy has grown substantially, as evidenced by the large number of U.S. Patents in the area now. Controlled release transdermal devices rely for their effect on delivery of a known flux of drug to the skin for a prolonged period of time, generally a day, several days, or a week. Two mechanisms are used to regulate the drug flux: either the drug is contained within a drug reservoir, which is separated from the skin of the wearer by a synthetic membrane, through which the drug diffuses; or the drug is held dissolved or suspended in a polymer matrix, and through which the drug diffuses to the skin. Devices incorporating a reservoir will deliver a steady drug flux across the membrane as long as excess undissolved drug remains in the reservoir; matrix or monolithic devices are typically characterized by a falling drug flux with time, as the matrix layers closer to the skin are depleted of drug. To date limited commercial exploitation of this technology has been achieved, because of the many practical problems to be overcome with real devices. The skin is an effective barrier against the majority of drugs. Unless the delivery device is made unacceptably large, or the natural skin permeation rate of the drug is somehow increased by the use of enhancers, then the drug flux across the skin is inadequate for useful therapy. Thus although in theory any drug might be delivered by this route, serious investigation of candidate drugs has been limited to those few that exhibit suitable properties, namely: small molecular size; short half-life; they are metabolized rapidly by the liver, and thus difficult to administer orally; high in vivo skin permeability; and small effective therapeutic dose. Despite active work in the field since at least 1970, at present commercial patches are available for delivery of only four drugs: nitroglycerin, scopolamine, clonidine, and estradiol. The U.S. Surgeon General has determined that cigarette smoking is a major risk factor in coronary heart disease and is the cause of approximately 30% of all cancer deaths. However, it is very difficult to give up smoking, and any smoking cessation therapy has to deal with both the pharmacological and the psychological dependence on cigarettes. Separating the treatment of these two factors is an approach that has been tried with modest success, for example by satisfying the pharmacological craving with nicotine pills or chewing
Patents 433
gum, while treating the psychological dependence. The difficulty with oral administration is that it leads to irregular and unpredictable blood plasma levels. To date, the best results have been obtained with nicotine chewing gum, which achieves direct delivery to the systemic circulation by buccal absorption. However, chewing gum formulations taste bad, may lead to mouth ulcers and heartburn, cannot be used effectively by denture wearers, and dosage control depends too much on patient compliance. Web site: http://www.delphion.com/details?pn=US04839174__ •
Oral osmotic device for delivering nicotine Inventor(s): Place; Virgil A. (Kawaihe, HI), Wong; Patrick S. L. (Palo Alto, CA), Barclay; Brian L. (Sunnyvale, CA), Childers; Jerry D. (Sunnyvale, CA) Assignee(s): Alza Corporation (Palo Alto, CA) Patent Number: 5,147,654 Date filed: November 15, 1991 Abstract: An osmotic device (10) for the controlled systemic delivery of nicotine through an oral mucosal membrane of a human patient is disclosed. The device (10) has a size and shape adapting it to be comfortably retained in the mouth for extended periods of time. The device (10) comprises a semipermeable wall (12) surrounding a compartment (13) containing a nicotine salt (14) and optionally an alkaline salt which is capable of reacting with the nicotine salt in the presence of water to form nicotine base. The conversion of nicotine salt to nicotine base may take place within the device (10) and/or outside the device and in the patient's mouth. Nicotine base and/or salt is delivered from the compartment (13) through a passageway (17) in the wall (12). The nicotine salt exhibits good stability and shelf life while the nicotine base exhibits excellent absorption through oral mucosal membranes. Excerpt(s): This invention pertains to an osmotic device for systemically delivering nicotine to a patient. More particularly, the invention relates to an osmotic device for systemically delivering nicotine base through the oral mucosal membranes of a patient. Systemic delivery of nicotine has been suggested as a treatment for smoking cessation. See "Longterm Effects of Transdermal Nicotine Substitution in Behavioral Smoking Cessation, " G. Buchkremer et al, Abstracts 6th World Conference on Smoking and Health, Nov. 9-12, 1987, Tokyo, Japan and "Nicotine Replacement: The Role of Blood Nicotine Levels, Their Rate of Change, and Nicotine Tolerance," M. Russell, Nicotine Replacement: A Critical Evaluation, pp 79-83 (1988). To date, nicotine replacement for smoking cessation has taken two forms: nicotine-containing chewing gum and transdermal nicotine delivery systems. See for example U.S. Pat. Nos. 3,845,217; 3,901,248; 4,597,961 and 4,758,434. In summary, the prior art has taught both the transdermal delivery of nicotine and the trans-oral-mucosal membrane delivery of nicotine from chewing gum as an aid to smoking cessation. When administering nicotine buccally from a chewing gum (i.e., by absorption of the drug through the highly vascularized buccal tissues of the mouth), a number of conditions are present which make it difficult to effectively deliver the nicotine in a controlled and therapeutically effective amount for a prolonged period of time (e.g., for periods greater than several minutes). The rate and vigor of chewing can vary greatly from patient to patient, thereby making controlled delivery of the nicotine nearly impossible. A further problem with chewing gums is that the patient's jaws become tired after extended chewing. This severely limit the time period for nicotine delivery.
434 Nicotine
Web site: http://www.delphion.com/details?pn=US05147654__ •
Pharmaceutical composition containing deoxypeganine for the treatment of nicotine dependence Inventor(s): Asmussen; Bodo (Bendorf, DE), Hille; Thomas (Neuwied, DE), Hoffmann; Hans-Rainer (Neuwied, DE), Opitz; Klaus (Munster, DE) Assignee(s): LTS Lohmann Therapie Systeme AG (Andernach, DE), HF Arzneimittelforschung GmbH (Werne, DE) Patent Number: 6,548,510 Date filed: July 19, 2001 Abstract: Desoxypeganine and its pharmaceutically acceptable acid addition salts are useful in treating nicotine dependence. Excerpt(s): This application is a 371 of PCT/EP00/00975 filed Feb. 8, 2000. The present invention relates to the novel use of a little-known active compound for the treatment of nicotine dependence. In particular, the present invention is directed at pharmaceutical use in formulations by means of which deoxypeganine or one of its pharmaceutically acceptable acid addition salts is delivered in a controlled, e.g. continuous, manner for the treatment of nicotine dependence. Web site: http://www.delphion.com/details?pn=US06548510__
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Pharmaceutical formulation for the treatment of nicotine dependence Inventor(s): Moormann; Joachim (Werne, DE) Assignee(s): Therapie-System GmbH & Co., KG (Neuwied, DE), Arzneimittelforschung GmbH & Co. KG (Werne, DE) Patent Number: 5,643,905 Date filed: October 30, 1995 Abstract: The present invention relates to the use of galanthamine and the pharmaceutically acceptable acid addition salts thereof for the treatment of nicotine dependence. The active substances are released from pharmaceutical formulations, e.g., orally, transdermally, or otherwise parenterally in a continuous and controlled manner. Excerpt(s): This application is a 371 of PCT/EP94/00055 filed Jan. 10, 1994. The present invention relates to pharmaceutical formulations for the treatment of nicotine dependence. The present invention is particularly directed to pharmaceutical formulations and devices by which galanthamine or one of its pharmaceutically acceptable acid addition salts is released in a controlled, for instance continuous manner to treat nicotine dependence. Web site: http://www.delphion.com/details?pn=US05643905__
Patents 435
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Plantago major and hypericum perforatum compound for use in treating a tobacco or nicotine habit Inventor(s): Cody; Mary E. (15 Meadowbrook Rd., Boonton Township, NJ 07005) Assignee(s): none reported Patent Number: 6,294,193 Date filed: March 14, 2000 Abstract: A composition containing the herbs Plantago major and Hypericum perforatum is presented. Use of the composition, of the present invention, in a form adapted to be orally ingested produces a diminished desire for tobacco (i.e., nicotine) without the use of nicotine itself and provides an anti-depressive effect. Excerpt(s): The present invention relates generally to an aid for use in treating a tobacco or nicotine habit. More particularly, the present invention relates to a composition containing as an active ingredient the herbs Plantago major and Hypericum perforatum for use as an aid in controlling a tobacco (i.e., nicotine) habit. The U.S. Surgeon General has determined that cigarette smoking is a major risk factor in coronary artery disease and is the cause of approximately 30% of all cancer deaths. Tobacco chewing has been shown to cause cancers of the mouth and throat. Because of the undesirable effects of tobacco smoking or tobacco chewing, many devices have been developed as aids for treatment of the tobacco and nicotine habit. For example, in a simulated smoking device, the tobacco therein is heated rather than burned, releasing nicotine vapor which is then drawn into the smoker's lungs. Thus, the smoker obtains the desired nicotine, but without also ingesting the full range and concentration of harmful products of burning tobacco. One such simulated smoking device using a source of vaporizable nicotine is disclosed in U.S. Pat. No. 4,284,089 issued to Ray. Other simulated smoking devices contain substances which microencapsulate materials that simulate the taste and aroma of tobacco, and which are then released by squeezing or crushing the device. Such devices often do not raise the nicotine level in the blood sufficiently to satisfy the desire for nicotine, and thus are ineffective as aids to stop smoking. Other disadvantages include irritation of the mucosa, which is intolerable to some patients, and the bad taste of nicotine introduced orally. Alternatively, tobacco concentrates have been processed into tablets or gum which may be sucked or chewed in the mouth of the user, the nicotine being absorbed into the user's body through the lining of the mouth. However, chewing gum formulations suffer from numerous drawbacks. They have a bad taste, they may lead to mouth ulcers and heartburn, they cannot be used effectively by denture wearers, and they depend on the patient following the prescribed chewing regime. Difficulties associated with oral administration of nicotine include nausea, rapid nicotine degradation, and irregular and unpredictable blood plasma levels. Inability to self-administer the gum while the patient is asleep leads to low or even zero levels of nicotine in the morning and a return of the smoking urge. Even with immediate administration of nicotine gum, it can take up to one hour before effective plasma levels of nicotine are again obtained. Web site: http://www.delphion.com/details?pn=US06294193__
436 Nicotine
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Preparation of continine by reacting nicotine with bromide and bromate Inventor(s): Rolf; David (Minneapolis, MN), Goon; David J. W. (Bloomington, MN), Michelson; Robert H. (Eagan, MN) Assignee(s): Lectec Corporation (Minnetonka, MN) Patent Number: 5,625,070 Date filed: June 7, 1995 Abstract: Cotinine is prepared from nicotine or nicotine sulfate by mixing a solution thereof with compounds having the formula XBr, YBrO.sub.3 where X is hydrogen or an alkali metal and Y is an alkali metal to produce an intermediate product: dibromocotinine hydrobromide perbromide, which is reduced and de-brominated to produce cotinine. Excerpt(s): This invention relates to the production of cotinine from nicotine. Cotinine has been synthesized by reacting bromine with nicotine to form an intermediate, dibromocotinine hydrobromide perbromide, which is then reduced by the addition of zinc and hydrochloric acid to yield cotinine (Biochemical Preparations, Vol. 10, pp. 3639). Japanese patent JP51105076A dated Sep. 17, 1976 describes another method wherein nicotine is reacted with hydrobromic acid and hydrogen peroxide to produce the intermediate which is reduced and debrominated by the usual method without isolation. In another method, cotinine was produced by oxidizing nicotine with a Hg(II)EDTA complex (Synthetic Communications, 18(12), pp. 1331-1337; 1988). A major object of the present invention is to avoid the use of toxic substances such as bromine, mercury and to avoid the combined use of hydrobromic acid and hydrogen peroxide as described in JP 51105076A because of the expense of HBr and because the yield of cotinine was found by us to be relatively poor. The use of toxic materials is particularly objectionable where the final product is to be formed without physical separation from the intermediate. In addition, safety problems are incurred and manufacturing costs are increased because of the special handling and treatment required for the toxic substances previously required. Accordingly, it is a major object of the present invention to provide an improved commercial method for producing cotinine in high yields and on a commercial scale without the drawback produced by the toxicity problems, poor yields, and costly reagents needed in previous methods. Web site: http://www.delphion.com/details?pn=US05625070__
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Procedure for producing low nicotine tobacco by means of high pressure extraction Inventor(s): Gahrs; Hans J. (Dusseldorf, DE) Assignee(s): Messer Griesheim GmbH (Frankfurt am Main, DE) Patent Number: 4,561,452 Date filed: August 27, 1984 Abstract: High pressure of nicotine with a compressed gaseous solvent is used for producing low nicotine tobacco. A mixture of nitrogen and carbon dioxide with the nitrogen being 50-80 percent of the mixture is used. The extraction is carried out at pressures between 250 and 600 bar at temperatures above 50.degree. C. Excerpt(s): The invention concerns a procedure for producing low nicotine tobacco by means of high pressure extraction of the nicotine, using a compressed gaseous solvent, as well as subsequent increase of the filling volume of the tobacco. By means of various
Patents 437
gaseous solvents under high pressure, it is possible to remove a significant portion of the nicotine from tobacco. The applied pressures can be so high that the solvents are in the liquid or in the overcritical condition. DE-OS No. 20 43 537 cites e.g., CO.sub.2, N.sub.2 O and Ar as suitable gaseous solvents. The disadvantage of this procedure is that in addition to the nicotine, other substances are partially extracted as well, e.g., those creating the aroma. According to a procedure known from the DE-OS No. 21 42 205, this disadvantage is avoided by extracting the aroma substances separately, prior to the de-nicotinization and adding these aroma substances back to the tobacco after extracting the nicotine. This procedure is relatively costly, and the possibility cannot be excluded that the aroma substances, which are partially complicated and sensitive, are negatively influenced by such manipulations. Another possibility to reduce the nicotine contents of tobacco products is to improve the fill volume of the tobacco used, i.e., to increase its specific volume (cm.sup.3 /g). For this purpose, the tobacco is impregnated with liquid or overcritical gases under pressure; subsequently, it is released and thermally after-treated by means of increased temperature. As suitable impregnation gases for this purpose, N.sub.2 or Ar are mentioned in DE-OS No. 29 03 300, liquid CO.sub.2 in U.S. Pat. No. 4,258,729. Web site: http://www.delphion.com/details?pn=US04561452__ •
Process and apparatus for the semicontinuous extraction of nicotine from tobacco Inventor(s): Prasad; Ravi (Midlothian, VA), Grubbs; Harvey J. (Mechanicsville, VA) Assignee(s): Philip Morris Incorporated (New York, NY) Patent Number: 5,497,792 Date filed: November 19, 1987 Abstract: A process is provided for the improved removal of nicotine from tobacco. An essentially nicotine-free solvent in the supercritical or liquid state is fed into a first end of an extraction flow system containing tobacco and a nicotine-rich solvent is discharged from a second end of the extraction flow system. Periodically a portion of extracted tobacco is discharged from the first end of the extraction system while simultaneously a portion of an unextracted tobacco is charged to the second end of the extraction system. Nicotine is then entrapped in an entrapment material or otherwise removed from the solvent and solvent is recycled through the extraction flow system. Various materials are provided as entrapment materials. Among the entrapment materials provided are aqueous solutions containing absorbent selected from various acids and salts. Among the acids and salts provided as entrapment materials are sulfuric acid, phosphoric acid, nitric acid, tartaric acid, citric acid, malic acid, lactic acid, malonic acid, succinic acid, acetic acid, glutamic acid and monopotassium citrate. Excerpt(s): This invention relates to extraction procedures and is particularly directed to a process for the semicontinuous extraction of materials from plant products. The invention may be used for the selective extraction of particular substances from a great variety of plant products, including caffeine and other xanthine derivatives from coffee beans and cacao and tea plant materials and products. However, it is particularly applicable and will therefore be described in connection with the extraction of nicotine from tobacco. Various processes have been proposed for the removal of nicotine from tobacco. Most of these processes, however, adversely affect the desirable flavor and aroma properties of the tobacco. Also, they are often complex and expensive to carry out. U.S. Pat. No. 4,153,063 (Roselius) discloses a process for removing nicotine from tobacco in which tobacco is contacted with an extraction solvent in a supercritical state.
438 Nicotine
It discloses both a single step extraction process and a multi-step extraction process. In the single step extraction process, moist tobacco is extracted with a solvent in a supercritical state. Because aroma components are also removed along with nicotine in this single step extraction process, the multi-step process is preferred. In the first step, dry tobacco is extracted with a solvent in the supercritical state to remove the aroma components. In the second step, the tobacco is moistened and again extracted with a solvent in the supercritical state to remove nicotine. The nicotine is separated from the solvent by either evaporating the solvent, contacting the solvent in a separate vessel with an acid, or adsorbing the nicotine on an active carbon column. In the third step, the stored aroma components from the first step are redissolved in a supercritical solvent and returned to the tobacco. This multi-step extraction process is expensive and time consuming. In addition, the prolonged handling of the aroma components may adversely affect their properties. Web site: http://www.delphion.com/details?pn=US05497792__ •
Process for maximizing the growth and nicotine degrading activity of microorganisms Inventor(s): Gravely; Lawrence E. (Louisville, KY), Geiss; Vernon L. (Floyd Knobs, IN), Newton; Richard P. (Louisville, KY) Assignee(s): Brown & Williamson Tobacco Corporation (Louisville, KY) Patent Number: 4,011,141 Date filed: November 17, 1975 Abstract: A process is disclosed for maximizing the growth and nicotine degrading activity of microorganisms effective to degrade nicotine through a biochemical mechanism in which 3-succinoylpyridine is formed. The process involves inoculating a nicotine-containing growth medium with the microorganisms and subjecting the broth to aeration and agitation. During the growth period, the broth should be maintained at a pH of between about 6 and 7.8 and at a temperature between about 10.degree. C and about 45.degree. C. The broth should have an initial nicotine concentration of at least 0.5 mg. per ml. up to an amount which is toxic to the microorganisms. Excerpt(s): The present invention pertains to a process for maximizing the growth and nicotine degrading activity of microorganisms used for treating tobacco to reduce its nicotine content. More specifically, the present invention pertains to a process for growing certain microorganisms, in a nicotine containing broth, under controlled conditions, whereby microorganism growth and nicotine degrading activity is maximized. For various reasons, it is often desirable to reduce the nicotine content of tobacco. For example, in recent years, low nicotine content "mild" cigarettes have gained substantial consumer acceptance. There are numerous techniques available for reducing the nicotine content of tobacco. However, most of these techniques result in the removal of other tobacco ingredients along with the nicotine. The removal of other ingredients adversely affects desirable flavor and taste properties, or other desirable smoking qualities. Thus, there is a need for techniques which are effective to selectively reduce the nicotine content of tobacco without deleteriously modifying its desirable smoking properties. Web site: http://www.delphion.com/details?pn=US04011141__
Patents 439
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Process for obtaining deproteinized tobacco freed of nicotine and green pigment, for use as a smoking product Inventor(s): Wildman; Samuel G. (Santa Monica, CA), Sheen; Shuh J. (Lexington, KY) Assignee(s): Leaf Proteins, Inc. (Carson, CA) Patent Number: 4,289,147 Date filed: November 15, 1979 Abstract: Described herein is a process for obtaining a smoking product from tobacco leaves. The leaves, or leaves and stalk together when immature plants are used in the process, are ground or otherwise pulverized to liberate the liquid portion of the leaves from the plant material. The liquid portion of the leaves is treated to remove watersoluble proteins and nicotine and the solid portion of the leaves is treated to remove water and insoluble protein material, nicotine and green pigment material. The residues obtained after separation of the water-soluble and -insoluble protein, nicotine and green pigment material are recombined to yield a processed tobacco which is suitable for use in cigarettes as a tobacco filler or other products of tobacco manufacture. Excerpt(s): In a broad aspect, this invention relates to a process for obtaining a smoking product from tobacco plants. In another and more specific aspect, it relates to a process for removing protein, nicotine and green pigment materials from tobacco which is to be used in cigarettes or other products of tobacco manufacture. This application is related to and incorporates by reference, as though fully set forth herein, the disclosure of the co-pending and commonly assigned application of S. G. Wildman and P. Kwanyuen, entitled "Process for Isolation of Proteins From Plant Leaves," filed Sept. 24, 1979, having Ser. No. 78,505. Cigarettes and other products of tobacco manufacture are, for the most part, blends of two principal types of tobacco, so-called "flue-cured" and "burley" tobaccos. American cigarettes, for example, are generally comprised of two-thirds fluecured tobacco and one-third burley tobacco. Web site: http://www.delphion.com/details?pn=US04289147__
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Process for reduction of nicotine content of tobacco by microbial treatment Inventor(s): Geiss; Vernon L. (Floyd Knobs, IN), Gregory; Charles F. (Louisville, KY), Newton; Richard P. (Louisville, KY), Gravely; Lawrence E. (Louisville, KY) Assignee(s): Brown & Williamson Tobacco Corporation (Louisville, KY) Patent Number: 4,140,136 Date filed: April 13, 1977 Abstract: A tobacco product having a reduced nicotine content. Tobacco is subjected, under controlled conditions, to the action of a microorganism effective to degrade nicotine through a biochemical reaction in which, inter alia, 3-succinoylpyridine is formed. Tobacco treated in accordance with this process, when incorporated into a tobacco smoking product, produces a mild smoke, having a reduced nicotine content. However, there is no loss of desirable flavor, taste and smoking properties. Excerpt(s): The present invention pertains to a process of reducing the nicotine content of tobacco by treating the tobacco with cultures of microorganisms. More specifically, the present invention pertains to a process for treating tobacco by subjecting it to the action of particular microorganisms, under controlled conditions, whereby the nicotine content of the tobacco is reduced in a relatively short time. The process is effective to
440 Nicotine
reduce the nicotine content of tobacco without substantially reducing the perceived strength of smoke generated by smoking articles produced from the tobacco. However, there is a reduction in irritating properties of smoke which is generated from tobacco treated by the process of the present invention. For various reasons, it is often desirable to reduce the nicotine content of tobacco. For example, in recent years, low nicotine content "mild" cigarettes have gained substantial consumer acceptance. There are numerous techniques available for reducing the nicotine content of tobacco. However, most of these techniques result in the removal of other tobacco ingredients along with the nicotine. The removal of other ingredients adversely affects desirable flavor and taste properties, or other desirable smoking qualities. Thus, there is a need for techniques which are effective to selectively reduce the nicotine content of tobacco without deleteriously modifying its desirable smoking properties. Web site: http://www.delphion.com/details?pn=US04140136__ •
Process for reduction of nitrate and nicotine content of tobacco by microbial treatment Inventor(s): Gravely; Lawrence E. (Louisville, KY), Geiss; Vernon L. (Floyd Knobs, IN), Gregory; Charles F. (Middletown, KY) Assignee(s): Brown & Williamson Tobacco Corporation (Louisville, KY) Patent Number: 4,557,280 Date filed: June 15, 1978 Abstract: A process for the reduction of the nitrate and nicotine contents of tobacco by microbial treatment is disclosed wherein tobacco materials are subjected, under controlled conditions, to the action of a microorganism effective to degrade nitrates and alkaloids (nicotine) through a biochemical reaction. The microorganism is combined or grown in the presence of a nitrate containing compound in relatively small quantities. Tobacco treated in accordance with this process has a reduced nitrate and nicotine content, and when incorporated into a tobacco smoking product thereby produces a mild smoke, having reduced nitrogen oxides, hydrogen cyanide and nicotine content. However, there is no loss of desirable flavor, taste and smoking properties. Excerpt(s): The present invention relates to a process of reducing the nitrate and nicotine contents of tobacco by treating the tobacco with a culture of a microorganism. More specifically, the invention relates to a process for treating tobacco to reduce the nitrate and nicotine contents thereof, which, when incorporated into a tobacco smoking product, yields smoke with reduced nitrogen oxides, hydrogen cyanide and nicotine deliveries without loss of desirable flavor and taste properties or other smoking qualities. For various reasons, it is often desirable to reduce the nitrate and nictone contents of tobacco. For example, in recent years, low nicotine content cigarettes have gained substantial consumer acceptance. Also, demand has increased for low delivery cigarettes and numerous techniques have become available for reducing either the nitrate content or the nicotine content of tobacco. In the removal or reduction of the nitrate content, the most common method has included the use of chemical agents in selective nitrate removal from tobacco extracts by ion retardation techniques. Reduction of nicotine content from tobacco has been accomplished by both chemical means as well as by microbial treatment. U.S. Pat. No. 4,011,141; U.S. Pat. No. 4,037,609; and, U.S. Pat. No. 4,038,993 teach microbial treatment means for the reduction of the nicotine content of tobacco. However, there is no treatment known which enables selective simultaneous
Patents 441
reduction of both the nitrate and nicotine content of tobacco in one treatment without reducing all flavor components, particularly one including the use of microorganisms. Web site: http://www.delphion.com/details?pn=US04557280__ •
Process for the extraction of nicotine from tobacco Inventor(s): Roselius; Wilhelm (Magnus, DE), Vitzthum; Otto (Bremen, DE), Hubert; Peter (Bremen-Lesum, DE) Assignee(s): Studiengesellschaft Kohle mbH (Mulheim, Ruhr, DE) Patent Number: 4,153,063 Date filed: August 23, 1973 Abstract: Process for extracting nicotine is disclosed in which tobacco is exposed to an extracting solvent in either liquid or gaseous state at temperatures below about 100.degree. C. and at high pressures. The aroma generating substances can be removed by conducting the extraction with the tobacco in dry condition. Thereafter the tobacco can be moistened, and on further contacting the nicotine is removed. The aroma generating substances can then be recombined with nicotine free tobacco. Excerpt(s): A number of processes have been studied and patented for the removal of toxic or otherwise offending substances from tobacco and like stimulants. It is known, for example, to extract nicotine from tobacco with solvents such as ammonia, ethylene oxide and the like. These and similar processes have not attained general acceptance due to the fact that the extraction solvents are not sufficiently selective and remove not only the nicotine, but varying amounts of the desirable constituents associated with the pleasant aroma of tobacco. The use of condensed gases has been studied quite extensively because of the known selective dissolving capacity of these substituents. The use of liquid SO.sub.2 has been described in German Patent No. 558,351, wherein a process for removing nicotine from tobacco is disclosed. This extraction solvent has not attained any appreciable acceptance due to the fact that SO.sub.2 is not sufficiently selective, may generate toxic residues and is highly corrosive to the apparatus employed. Accordingly, the art has long concerned itself with the problem of selective extraction of nicotine from tobacco with nontoxic solvents which do not corrode the apparatus employed. Web site: http://www.delphion.com/details?pn=US04153063__
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Process for the inclusion of a solid particulate component into aerosol formulations of inhalable nicotine Inventor(s): Jacobs; Allen W. (12534 Oxnard St., #6, North Hollywood, CA 91606) Assignee(s): none reported Patent Number: 4,635,651 Date filed: August 29, 1980 Abstract: This invention provides a process for the inclusion of a solid particulate component into self-propelled aerosol formulations of inhalable nicotine. Excerpt(s): Ser. No. 830,052, filed Sept. 2, 1977 in the name of Allen W. Jacobs now abandoned. Numerous attempts have been made and means proposed to eliminate or
442 Nicotine
lessen many of the negative and dangerous effects from the consumption of nicotine and cannabis. Herein, nicotine is used to refer to itself, the major active substance in tobacco. Also it is intended to refer to all relevant tobacco-like products, nicotine salts, derivatives, precursors, and those substances known to have nicotine-like effects, such as lobeline, the tetramethylamonium family of salts, etc. Cannabis is intended to refer to all of the relevant known substances found in the Cannabis family of plants. Also, it is intended to include all relevant cannabis-like products, natural and synthetic cannabis isomers, and other derivatives, precursors, metabolites, etc., or related substances having cannabis like effects. While many means of consumption are known, not all are practical. The act of smoking, thus far, has proven to be one of the most direct, simple, and convenient means of intake of these substances. Web site: http://www.delphion.com/details?pn=US04635651__ •
Process of preparing nicotine N'-oxide and smoking products containing it Inventor(s): Schmekel; Gerald (Elmshorn, DE), Rudolph; Gert (Hamburg, DE) Assignee(s): B.A.T. Cigarettenfabriken GmbH (DE) Patent Number: 4,641,667 Date filed: December 7, 1984 Abstract: Smoking products, for example cigarettes, cut tobacco, pipe tobacco, cigarillos and the like, give an increased yield of nicotine in the tobacco smoke without impairment of the taste of the smoke, when trans-nicotine N'-oxide, which is free or substantially free of cis-nicotine N'-oxide or contains at most 10% by weight of the cisisomer, is added thereto in a quantity of up to 5% by weight, relative to the dry weight of the tobacco. The nicotine N-oxide is prepared by oxidizing nicotine with an aqueous H.sub.2 O.sub.2 solution in the presence of a catalytic amount of non-oxidizing acid having a pk value of less than 5 to produce an oxidation mixture containing trans and cis-nicotine N'-oxide. Excerpt(s): The invention relates to a smoking product, in particular tobacco with or without a wrapper material, which contains nicotine N'-oxide. Furthermore, the invention relates to a process for the preparation of trans-nicotine N'-oxide, which is free or substantially free of cis-nicotine N'-oxide, in particular for use as an additive to smoking products of the invention. The invention also relates to a process for the preparation of trans-nicotine N'-oxide which is free or substantially free of cis-nicotine N'-oxide. The process requires short reaction periods and only auxiliary substances which are acceptable under foodstuffs law are used. Web site: http://www.delphion.com/details?pn=US04641667__
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Prolonged activity nicotine patch Inventor(s): Baker; Richard W. (Palo Alto, CA), Kochinke; Frank (Fremont, CA), Huang; Carl (Palo Alto, CA) Assignee(s): Pharmetrix Corporation (Menlo Park, CA) Patent Number: 4,943,435 Date filed: October 28, 1988
Patents 443
Abstract: A transdermal patch for delivering nicotine for prolonged periods of 12-24 hours. The patch includes a rate-controlling membrane or monolith to keep the nicotine flux within useful and safe limits. The patch is typically replaced once a day, and can be used for smoking cessation therapy or in other situations where systemic nicotine delivery is indicated. Excerpt(s): The invention relates to a transdermal patch for administering nicotine. More particularly, the invention concerns patches that can deliver an appropriate dosage of nicotine for a period of a day or more. Delivery of drugs by the transdermal route has been known to be theoretically possible for many years. The earliest developed transdermal patches were medicated bandages, usually with the drug mixed into the adhesive, designed to bring a known quantity of drug to a known area of skin for a known time. Such devices do not control the rate at which the drug is released. Controlled release transdermal patches rely for their effect on delivery of a known flux of drug to the skin for a prolonged period of time, measured in hours, days or weeks. Two mechanisms are used to control the drug flux from the patch: either the drug is contained within a drug reservoir, separated from the skin of the wearer by a synthetic membrane, through which the drug diffuses; or the drug is held dissolved or suspended in a polymer matrix, through which the drug diffuses to the skin. Patches incorporating a reservoir and membrane will deliver a steady drug flux across the membrane as long as excess undissolved drug remains in the reservoir; matrix or monolithic devices are typically characterized by a falling drug flux with time, as the matrix layers closer to the skin are depleted of drug. To date limited commercial exploitation of the transdermal administration route has been achieved, because of the many practical problems to be overcome with real systems. The skin is an effective barrier against the majority of drugs. Unless the delivery device is made unacceptably large, or the natural skin permeation rate of the drug is increased, then the drug flux across the skin is inadequate for useful therapy. Thus although in theory any drug might be delivered by this route, serious investigation of candidate drugs has been limited to a few where there are strong indications for transdermal use, namely: small molecular size; short half-life; rapid metabolization by the liver, rapid degradation in the GI tract; other problems with oral administration; high in vivo skin permeability; and high potency, i.e. small effective therapeutic dose. Despite active work in the field since at least 1970, at present commercial patches are available for delivery of only four drugs: nitroglycerin, scopolamine, clonidine, and estradiol. The U.S. Surgeon General has determined that cigarette smoking is a major risk factor in coronary heart disease and is the cause of approximately 30% of all cancer deaths. However, it is very difficult to give up smoking, and any smoking cessation therapy has to deal with both the pharmacological and the psychological dependence on cigarettes. Separating the treatment of these two factors is an approach that has been tried with modest success, for example by satisfying the pharmacological craving with nicotine pills or chewing gum, while treating the psychological addiction independently. To date, the best results have been obtained with nicotine chewing gum, which achieves direct delivery to the systemic circulation by buccal absorption. However, chewing gum formulations taste bad, may lead to mouth ulcers and heartburn, cannot be used effectively by denture wearers, and depend entirely on the patient following the prescribed chewing regime. Other difficulties associated with oral administration include stomach upsets, nausea, rapid nicotine degradation, and irregular and unpredictable blood plasma levels. Web site: http://www.delphion.com/details?pn=US04943435__
444 Nicotine
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Protein involved in nicotine synthesis, DNA encoding, and use of sense and antisense DNAs corresponding thereto to affect nicotine content in transgenic tobacco cells and plants Inventor(s): Wahab; Samir Z. (Richmond, VA), Malik; Vedpal S. (Richmond, VA) Assignee(s): Philip Morris Incorporated (New York, NY) Patent Number: 5,668,295 Date filed: March 3, 1995 Abstract: Nicotine acid sequences encoding a tobacco protein involved in nicotine synthesis are described. These sequences, when inserted in to sense or anti-sense orientation, affect nicotine synthesis in transgenic tobacco plants. Excerpt(s): The present invention relates to a highly purified tobacco protein involved in photosynthesis, to a novel process for its purification, and to its antisense and sense genes. In particular, this invention relates to the use of the sense and antisense genes encoding this protein to create transgenic tobacco plants having genetically altered nicotine levels. Such transgenic plants are useful in the production of cured tobacco for use in the tobacco industry. Various processes have been employed for the removal of nicotine from tobacco. Most of those processes, however, are not sufficiently selective for nicotine. They remove other ingredients from the tobacco, thereby adversely affecting its flavor and aroma. In addition, such processes are typically complex and expensive. Nicotine, and biologically synthesized compounds in general, are formed through sequences of biochemical reactions, wherein each reaction is catalyzed by a different enzyme. The particular reaction sequence leading to a given compound is known as a pathway. One approach for inhibiting the operation of a pathway, and thus output of its end product, is reducing the amount of a required enzyme in the pathway. If the enzyme's abundance, relative to the other enzymes of the pathway, is normally low enough to make that enzyme rate-limiting in the pathway's operation, then any reduction in the enzyme's abundance will be reflected in lowered production of the end product. If the enzyme's relative abundance is not normally rate limiting, its abundance in the cell would have to be reduced sufficiently to make it rate-limiting, in order for the pathway's output to be diminished. Similarly, if the enzyme's relative abundance is rate limiting, then any increase in its abundance will result in increased production of the pathway's end product. Web site: http://www.delphion.com/details?pn=US05668295__
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Purified tobacco protein involved in nicotine synthesis, DNA encoding, and use of sense and antisense DNAs corresponding thereto to affect nicotine content in tobacco plants Inventor(s): Nakatani; Herbert Y. (Midlothian, VA), Malik; Vedpal S. (Richmond, VA) Assignee(s): Philip Morris Incorporated (New York, NY) Patent Number: 5,684,241 Date filed: October 17, 1994 Abstract: Nicotine acid sequences encoding a tobacco protein involved in nicotine synthesis are described. These sequences, when inserted in to sense or anti-sense orientation, affect nicotine synthesis in transgenic tobacco plants.
Patents 445
Excerpt(s): The present invention relates to highly purified tobacco protein involved in nicotine synthesis, to a novel process for its purification, and to its antisense and sense genes. In particular, this invention relates to the use of the sense and antisense genes encoding this protein to create transgenic tobacco plants having genetically altered nicotine levels. Such transgenic plants are useful in the production of cured tobacco for use in the tobacco industry. Various processes have been employed for the removal of nicotine from tobacco. Most of those processes, however, are not sufficiently selective for nicotine. They remove other ingredients from the tobacco, thereby adversely affecting its flavor and aroma. In addition, such processes are typically complex and expensive. Nicotine, and biologically synthesized compounds in general, are formed through sequences of biochemical reactions, wherein each reaction is catalyzed by a different enzyme. The particular reaction sequence leading to a given compound is known as a pathway. One approach for inhibiting the operation of a pathway, and thus output of its end product, is reducing the amount of a required enzyme in the pathway. If the enzyme's abundance, relative to the other enzymes of the pathway, is normally low enough to make that enzyme rate-limiting in the pathway's operation, then any reduction in the enzyme's abundance will be reflected in lowered production of the end product. If the enzyme's relative abundance is not normally rate limiting, its abundance in the cell would have to be reduced sufficiently to make it rate-limiting, in order for the pathway's output to be diminished. Similarly, if the enzyme's relative abundance is rate limiting, then any increase in its abundance will result in increased production of the pathway's end product. Web site: http://www.delphion.com/details?pn=US05684241__ •
Removal of nicotine from tobacco smoke Inventor(s): Browne; Colin L. (Clover, SC), Robertson; Raymond M. (Pineville, NC) Assignee(s): Hoechst Celanese Corporation (Somerville, NJ) Patent Number: 5,462,072 Date filed: January 18, 1994 Abstract: The instant invention is directd to the removal of nicotine from tobacco smoke by the use of compounds containing a metal with a valence of +2. Excerpt(s): This invention is directed to the removal of nicotine from tobacco smoke by the use of compounds containing a metal having a valence of +2. Tobacco smoke contains many different chemical compositions, one of which is nicotine. The removal of nicotine from tobacco smoke could have a beneficial affect upon tobacco smoking products. Various components of tobacco smoke have been eliminated by use of metal ions in the form of compounds that are adsorbed or otherwise impregnated onto the surface of the materials that can be incorporated into a filter of a smoking device. For example, in U.S. Pat. No. 3,724,469, the removal of nitrogen oxides from cigarette smoke was accomplished by the use of cobalt or iron chelates absorbed or supported on the surface of a suitable particulate support (for example activated carbon particles) which were disposed within a cigarette filter. In Japanese Kokai Patent No. 59 [1984]- 16540, the absorbency of tobacco filters for substances, such as ammonia, mercaptan, etc., was enhanced by impregnating the filter with a metal tannate chelate compound. One such metal tannate chelate was formed by the reaction of ferric chloride (FeCl.sub.3) and tannic acid. Web site: http://www.delphion.com/details?pn=US05462072__
446 Nicotine
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Salts provided from nicotine and organic acid as cigarette additives Inventor(s): Lawson; Jerry W. (Clemmons, NC), Bullings; Bruce R. (Winston-Salem, NC), Perfetti; Thomas A. (Winston-Salem, NC) Assignee(s): R. J. Reynolds Tobacco Company (Winston-Salem, NC) Patent Number: 4,830,028 Date filed: February 10, 1987 Abstract: Cigarettes having incorporated therein a salt such as nicotine levulinate exhibit low FTC "tar" to nicotine ratios while (i) having a smooth, palatable, flavorful taste, and (ii) providing smoking satisfaction to the user. The cigarettes do not exhibit a harsh or irritating character; and do not exhibit a non-tobacco or off-taste. Excerpt(s): The present invention relates to smoking articles such as cigarettes, and in particular to those smoking articles having incorporated therein an additive comprising nicotine and an organic acid. Popular smoking articles such as cigarettes have a substantially cylindrical rod shaped structure and include a charge of smokable material such as particulates of tobacco (i.e., cut filler) surrounded by a wrapper such as paper thereby forming a tobacco rod. It has become desirable to manufacture cigarettes having cylindrical filters aligned in an end-to-end relationship with the tobacco rod. Typically, filters are manufactured from fibrous materials such as cellulose acetate and are attached to the tobacco rod using a circumscribing tipping material. The so called "full flavor" cigarettes are popular smoking articles which delivers a desirable tobacco taste, flavor and satisfaction to the smoker. Typically, the "full flavor" cigarettes deliver about 14 mg or more of FTC "tar" per cigarette. Cigarettes also can be classified as "full flavor low tar" cigarettes. Typically, the "full flavor low tar" cigarettes deliver from about 8 to about 14 mg of FTC "tar" per cigarette, as well as lower levels of FTC nicotine as compared to "full flavor" cigarettes. Yet another classification of popular cigarettes is the "ultra low tar" cigarette which delivers still lower levels of FTC "tar" and nicotine. Typically, the "ultra low tar" cigarettes deliver less than about 7 mg of FTC "tar" per cigarette. The "full flavor low tar" and "ultra low tar" cigarettes conventionally have air dilution means such as laser perforations provided in the periphery of the mouth end region thereof, or have filter elements highly efficient for the removal of "tar" and nicotine from the mainstream aerosol. In general, the perceived taste or strength of the cigarettes classified as having lower levels of "tar" and nicotine are progressively less than that of the cigarettes which are classified as approaching the characteristics of the "full flavor" cigarettes. It has been proposed to add nicotine and other flavorants to the cut filler of lower "tar" cigarettes to enhance the taste, strength and satisfaction of such cigarettes. However, the addition of nicotine to such cigarettes generally yields mainstream smoke which may be perceived as harsh or irritating to the mouth, nose and throat of the user. Web site: http://www.delphion.com/details?pn=US04830028__
Patents 447
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Selective delivery and retention of nicotine by-product from cigarette smoke Inventor(s): Cohen; Richmond R. (Hockessin, DE), Gibboni; David J. (Drexel Hill, PA) Assignee(s): Hercules Incorporated (Wilmington, DE) Patent Number: 4,896,683 Date filed: October 17, 1988 Abstract: A method for controlling nicotine delivery through a cigarette filter relative to total particulate pass-through concentration, and the corresponding filter utilizing, as a filter modifier component, at least one water-soluble metal salt of a weak acid, the choice and amount of salt within the filter favoring an alkaline pH exceeding about pH 8, the amount of alkalinity being correlated to the desired amount of nicotine passthrough while corresponding nicotine filter retention properties are keyed to the presence and concentration of a water soluble salt of a strong acid within the filter. Excerpt(s): The present invention relates to an improved cigarette filter and method for selectively controlling nicotine delivery relative to delivered particulate matter from cigarette smoke by using a cigarette filter element containing at least one active water soluble modifier component. Although fiber-based cigarette filter elements are well known and have been used for a number of years, the choice of components for this class of filters has remained quite limited over the years due to cost factors and lack of general suitability of many natural fibers for high speed filter production using state of the art filter rod-making apparatus. In addition, the demands on present day commercial cigarette filter elements tend to conflict, particularly with respect to general filtration efficiency and increased demand for selective filtration of cigarette smoke components. While various fibers and fiber mixtures have been tried and evaluated, a substantial number of cigarette filter elements continue to favor old technology because of certain cost and handling advantages. For example, cellulose acetate tow can be readily processed into cuttable filter rods using an essentially unmodified state-of-the art filter rod-making apparatus without serious jamming problems. This advantage is enjoyed despite increased need for substantial amounts of additives, including organic plasticizers such as triacetin, diacetin, citric acid, as well as lubricants, flavors, medicines, selective filtering agents and the like. Generally, such additives are applied as aqueous solutions onto opened fiber tow by art-recognized dipping, spraying, or printing techniques. Web site: http://www.delphion.com/details?pn=US04896683__
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Selectively removable nicotine-containing dosage form for use in the transmucosal delivery of nicotine Inventor(s): Stanley; Theodore H. (Salt Lake City, UT), Hague; Brian (West Valley City, UT) Assignee(s): University of Utah Research Foundation (Salt Lake City, UT) Patent Number: 5,783,207 Date filed: February 4, 1997 Abstract: The present invention relates to a selectively removable nicotine-containing dosage form for use in the transmucosal delivery of nicotine to a patient. More specifically, the present invention is directed to a nicotine-containing dosage-form comprising an attached holder member which may be used to manipulate the dosage
448 Nicotine
form within the mouth of the patient as part of an effective smoking cessation program or in situations where smoking is undesirable or not permitted. Nicotine is released from a dosage form and absorbed through the intra-oral mucosal surfaces as the nicotine-containing matrix releases nicotine within the user's mouth. The user may selectively insert and remove the dosage form as desired to control the release of nicotine. In addition, the user may manipulate the dosage form by use of the holder means in such a manner to meet the user's psychological need or desire for ritualistic oral stimulation similar to cigarette smoking. Excerpt(s): The present invention relates generally to a cigarette substitute for administering a dose of nicotine. More specifically, the present invention is directed to a nicotine-containing dosage-form having a holder which may be used as part of an effective smoking cessation program or in situations where smoking is undesirable or not permitted. Nicotine is a naturally occurring drug found in tobacco which has both stimulant and depressant effects in the peripheral and central nervous systems. Nicotine can thus be included in a broad category of CNS-acting drugs. Nicotine occurs as a basic, colorless to pale yellow, very hygroscopic, oily, volatile liquid that has an unpleasant pungent order and a sharp, burning, persistent taste. Nicotine forms salts with almost any acid and therefore exists in a variety of salt forms. Nicotine is considered to be very toxic and toxic effects develop rapidly following an acute overdose. When nicotine is obtained from tobacco, as by chewing, snuffing or smoking, the amount of nicotine absorbed into the body generally does not build up to a toxic level. Nicotine can be introduced into the body through many different routes. One of the most popular versions of nicotine use involves the smoking of cigarettes. When the tobacco in a cigarette is ignited, the combustion process causes the release of nicotine vapors. The nicotine in cigarette smoke, suspended on minute particles of "tar" is quickly absorbed through the lung. The absorption of nicotine into the body through cigarette smoke is almost as quick as intravenous administration, with the nicotine reaching the brain within eight seconds after inhalation of the tobacco smoke. Web site: http://www.delphion.com/details?pn=US05783207__ •
Smoking products comprising nicotine substitutes Inventor(s): Grigg; Ronald E. (The Queen's University of Belfast, Dept. of Chemistry, David Keir Bldg., Belfast, BT9 5AG, GB5), Amornraksa; Kitti (The Queen's University of Belfast, Dept. of Chemistry, David Keir Bldg., Belfast, BT9 5AG, GB5) Assignee(s): none reported Patent Number: 4,600,025 Date filed: May 6, 1983 Abstract: A smoking product comprising an inert combustible substrate to which has been applied a nicotine-substitute-effective amount of a compound selected from the group consisting of 2-methyl-5-(pyrrolidinomethyl) thiazole and 2-methyl-5(piperidinomethyl) thiazole, and the acid addition salts thereof. Thus, for example, a cigarette may include an inert combustible material which is a tobacco substitute onto which one or other effective compound has been impregnated. Excerpt(s): The compounds exemplified by Poittevain et al. are those of formula I in which R.sup.2 and R.sup.3 are each H, CH.sub.3 or HOCH.sub.2 CH.sub.2, and also 2methyl-5-(piperidinomethyl)thiazole hemiethanedisulphonate and 2-methyl-5-(4methylpiperazinomethyl)thiazole. The compounds are associated with anti-lipolytic
Patents 449
activity, in that they reduce the amount of plasma free fatty acids, and hypoglycaemic activity. Pharmaceutical compositions are described, but the only specific examples of compositions, and the only test results (given in the corresponding French Publications Nos. 2,323,383 and 2,372,678) relate to compounds in which R.sup.2 and R.sup.3 are each hydrogen, alkyl or hydroxyalkyl, except for a LD.sub.50 test on the 4-methylpiperazino derivative. U.S. Pat. Specification No. 3,966,950 describes 2-alkyl-5thiazolecarboxamides having.alpha.-adrenolytic activity. French Patent Publication No. 2,209,557 discloses, as intermediates, 2-propyl-5-thiazolecarboxamides. It has now been discovered that 2-methyl-5-(piperidinomethyl)thiazole and the novel compound 2methyl-5-(pyrrolidinomethyl)thiazole and their acid addition salts, are of utility in stimulation of the central nervous system. These compounds can be prepared by reduction of the novel compounds 2-methyl-5-(piperidinocarbonyl)-thiazole and 2methyl-5-(pyrrolidinocarbonyl)thiazole, respectively. Web site: http://www.delphion.com/details?pn=US04600025__ •
Solution containing nicotine Inventor(s): Westman; Eric C. (Durham, NC), Rose; Jed E. (Durham, NC), Tomlin; Keith F. (Raleigh, NC) Assignee(s): Duke University (Durham, NC) Patent Number: 6,211,194 Date filed: April 30, 1998 Abstract: A nicotine method and solution which utilizes an acidic solution containing nicotine. The solution is for use to treat various medical conditions, such as to reduce the need of a user of smoking tobacco to smoke tobacco, to reduce attention deficit disorder symptoms in a person who has attention deficit disorder, and/or to reduce Alzheimer's disease symptoms in a person who has Alzheimer's disease. The solution is palatable and may be introduced into the person by the person drinking it. Subsequent to drinking, the blood plasma levels are sufficient to reduce the need to smoke tobacco, to reduce attention deficit disorder symptoms, and/or to reduce Alzheimer's disease symptoms. Excerpt(s): The present invention relates in general to a smoking cessation aid, and more particularly to a nicotine containing solution useful as a smoking cessation aid to a user of smoking tobacco, and which is palatably acceptable to the user upon drinking by the user and which provides a sufficient amount of nicotine to the blood in order to reduce the need of the user to smoke tobacco. The nicotine solution is also useful in treating medical conditions other than addiction to the smoking of tobacco products, such as in treating attention deficit disorder and in treating Alzheimer's. Implicated in over one of every six deaths, cigarette smoking is the leading preventable cause of death in the United States. See, U.S.D.H.H.S., "The Health Benefits of Smoking Cessation", A Report of the Surgeon General. Rockville. Md.: Public Health Service (1990). Unfortunately, nearly 50 million Americans continue to smoke. See, "Cigarette Smoking Among Adults-United States", Centers for Disease Control and Prevention, (1992), and "Changes in Definition of Smoking", JAMA, Vol. 272, pp. 14-16 (1994). With currently available treatment, long-term smoking abstinence rates are generally less than 30%. See, Fiore, Smith, and Baker, "The Effectiveness of the Nicotine Patch in Smoking Cessation", JAMA, Vol. 271, pp. 1940-1947 (1994). With the increasing recognition of the health hazards associated with the smoking of tobacco, particularly cigarette smoking, increasing attention has been focused on less harmful means to provide some of the
450 Nicotine
satisfaction obtained by smoking. By temporarily giving the smoker an alternative source of nicotine, smoking withdrawal symptoms can be relieved and smoking abstinence facilitated. Some of the alternative sources rely on nicotine replacement through nicotine chewing gum, nicotine skin patches, nicotine nasal sprays, or nicotine vapor inhalers. See, Rose, J. E., "Nicotine Addiction and Treatment", Ann. Rev. Med., Vol. 47, pp. 493-507 (1996). Also, buccal administration of a nicotine lozenge that has an alkaline pH is shown in U.S. Pat. No. 5,549,906 issued Aug. 27, 1996 to Santus. Web site: http://www.delphion.com/details?pn=US06211194__ •
Spinal cord stimulation as a treatment for addiction to nicotine and other chemical substances Inventor(s): Hess; Carl A. (23772 Medinah La., Laguna Niguel, CA 92677) Assignee(s): none reported Patent Number: 6,233,488 Date filed: June 25, 1999 Abstract: A new method for suppressing chemical substance craving comprises an electrical stimulation of the spinal cord using one or more implantable leads containing at least two conducting electrodes. The method may be used to suppress craving for alcohol, narcotics, cocaine, and amphetamines. The method is particularly suited to the suppression of nicotine craving. Excerpt(s): The present invention relates to a new method for suppressing chemical substance craving comprising electrical stimulation of the spinal cord using one or more implantable leads containing at least two conducting electrodes. The method may be used to suppress craving for alcohol, narcotics, cocaine and amphetamines. The method is particularly suited to the suppression of nicotine craving. Tobacco related deaths are the largest single cause of premature death in developed countries. More than 400,000 deaths per year are linked to smoking related illness in the U.S. alone. However, despite the well publicized risks and consequences associated with tobacco use, more than 25% of adults in the United States continue to smoke with prevalence rates varying according to demographics. The benefits of smoking cessation are substantial. Immediate benefits accrue to smokers who quit, including those with smoking-related disease. The risk of disease declines with smoking cessation and continues to drop through periods of abstinence. After 10-15 years of abstinence, mortality risks are equal to those of nonsmokers. Smoking cessation decreases the risk of stroke, aortic aneurysm, peripheral vascular disease and myocardial reinfarction in individuals with myocardial infarction. Similar risk reduction exists in the incidence of smoking related cancers, chronic obstructive pulmonary disease and pregnancy related complications. An effective treatment for smoking addiction would result in a significant public health advance. Web site: http://www.delphion.com/details?pn=US06233488__
Patents 451
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Subsaturated nicotine transdermal therapeutic system Inventor(s): Osborne; James L. (Mountain View, CA), Nelson; Melinda (Sunnyvale, CA), Enscore; David J. (Saratoga, CA), Yum; Su I. (Los Altos, CA), Gale; Robert M. (Los Altos, CA) Assignee(s): Alza Corporation (Palo Alto, CA) Patent Number: 5,364,630 Date filed: June 21, 1993 Abstract: Rate controlled transdermal nicotine delivery systems are disclosed which utilize an in-line adhesive to maintain the systems on the skin. The initial equilibrated concentration of nicotine in the nicotine reservoir and the adhesive is below saturation, preferably at a thermodynamic activity no greater than 0.50, and the reservoir comprises the nicotine dissolved in a material with respect to which the rate controlling element of the device is substantially impermeable. In preferred embodiments the initial loading of nicotine in the reservoir is sufficient to prevent the activity of the nicotine in the reservoir from decreasing by more than about 75% and preferably no more than about 25% during the predetermined period of administration; and the thickness of the adhesive, rate controlling membrane and reservoir layers are selected so that at least 50% and, preferably at least 75% of the initial equilibrated nicotine loading is in the reservoir layer. Excerpt(s): This invention relates to transdermal delivery systems for delivering nicotine through skin for an extended period of time and more particularly to such a system which utilizes a rate controlling membrane and an in-line adhesive. The device is used to assist a smoker to stop smoking. Transdermal devices for the delivery of a wide variety of biologically active agents have been known for some time and representative systems which utilize rate controlling membranes and in-line adhesives are disclosed in U.S. Pat. Nos. 3,598,122; 3,598,123; 3,742,951; 4,031,894, 4,144,317; 4,201,211 and 4,379,454 which are incorporated herein by reference. Such devices generally comprise an impermeable backing, a drug or active agent reservoir, a rate controlling membrane and a contact adhesive layer which can be laminated or heat sealed together to produce a transdermal delivery device. It has also been proposed to deliver nicotine transdermally to aid in the cessation of smoking, see for example U.S. Pat. Nos. 4,597,961 and 4,839,174 which are incorporated herein by reference. Web site: http://www.delphion.com/details?pn=US05364630__
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Tablet giving rapid release of nicotine for transmucosal administration Inventor(s): Wilhelmsen; Paul C (281 Livoina Hgts, Alamo, CA 94507) Assignee(s): none reported Patent Number: 6,248,760 Date filed: April 14, 1999 Abstract: A tablet for the transmucosal administration of nicotine. The nicotine is in one or more layers upon a non-nicotine containing matrix. The nicotine layers rapidly dissolve in the mouth. The nicotine is then rapidly absorbed by the intra-oral mucosal surfaces. The short, rapid pulse of nicotine is similar to that given by cigarette smoking. The nicotine may be provided in a plurality of layers separated by one or more layers that are essentially free of nicotine to support the nicotine layers.
452 Nicotine
Excerpt(s): The present invention relates to a tablet for transmucosal administration of a medicament. Specifically, it relates to a tablet that will give a rapid release of nicotine. Nicotine is the most widely distributed of the plant alkaloids. It occurs in two separate phyla of the plant kingdom, Pteridophytes and Spermatophytes. Despite its wide distribution, for practical purposes, nicotine is obtained from the tabacum and rustica species of the Nicotina genus. However, it is interesting that Australian Aboriginal people chewed "pituri", a nicotine preparation made from Duboisia hopoodi. Nicotine can be isolated as an oily, volatile base with a sharp burning taste. Nicotine will form acid salts with most acids. Nicotine can be introduced into the body in many ways. The most popular way is by smoking cigarettes. When a cigarette is smoked, the partial oxidation of the tobacco causes the vaporizing of some of the nicotine. The nicotine vapor as well as nicotine adsorbed on partial oxidation products of the cigarette is quickly absorbed through the lungs. A dozen beats of the heart can carry nicotine from the lungs to the brain in less than 20 seconds. Web site: http://www.delphion.com/details?pn=US06248760__ •
Tobacco cembranoids block the expression of the behavioral sensitization to nicotine and inhibit neuronal acetylcholine receptors Inventor(s): Eterovic; Vesna A. (Rio Piedras, PR), Ferchmin; Pedro A. (Rio Piedras, PR), Hann; Richard M. (Guaynabo, PR), Pagan; One R. (Ithaca, NY), Rodriguez; Abimael D. (Rio Piedras, PR), Rosario; Osvaldo (Rio Piedras, PR) Assignee(s): University of Puerto Rico (San Juan, PR), Universidad Central del Caribe Bayamon (PR) Patent Number: 6,489,357 Date filed: October 21, 2000 Abstract: The subject invention relates the use of cembranoids to inhibit nicotine addiction at the behavioral level. The subject host is sensitized to nicotine. Cembranoids are then administered to reduce such sensitization. Excerpt(s): Despite the consensus that nicotine is the compound responsible for the addictive properties of cigarettes, other factors may contribute to this addiction. Besides nicotine, tobacco contains thousands of other compounds among which there is a family of cyclic diterpenoids called cembranoids. Cyclic diterpenoids are also found in marine invertebrates, specifically Gorgonian species (soft corals). According to another aspect of the invention, administering cembranoids to a living host reduces sensitization to nicotine. According to further aspects of the invention, the living host is sensitized to nicotine by regular administration of nicotine to the living host. The cembranoids are administered after the regular administration of nicotine to the living host. The cembranoids may all be the same compound or may be a plurality of different compounds, including eunicin, eupalmerin acetate, 12,13-bisepieupalmerin, 4Scembratriene and 4R-cembratriene. Web site: http://www.delphion.com/details?pn=US06489357__
Patents 453
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Tobacco compositions, method and device for releasing essentially pure nicotine Inventor(s): Lilja; Jan E. (Kristianstad, SE), Lilja; Jan E. (Kristianstad, SE), Nilsson; Sven E. L. (Helsingborg, SE), Nilsson; Sven E. L. (Helsingborg, SE) Assignee(s): AB Leo (Helsingborg, SE), AB Leo (Helsingborg, SE) Patent Number: 4,907,606 Date filed: January 26, 1988 Abstract: Novel tobacco compositions which when subjected to an elevated temperature below the combustion temperature the tobacco liberates essentially pure nicotine. The invention also includes a method for liberating nicotine from the compositions and a device for carrying out the method. Excerpt(s): The present invention concerns tobacco compositions and a non-combustion method of liberating essentially pure nicotine from such compositions. It also includes a device for carrying out the method. The present invention concerns tobacco compositions and a non-combustion method of liberating essentially pure nicotine from such compositions. It also includes a device for carrying out the method. It is now widely recognized that smoking can be a major health hazard. This hazard can be cut down by reducing or eliminating smoking, but smokers find this extremely difficult and it is generally accepted that this difficulty is caused by nicotine-dependence. While the presence of nicotine in tobacco smoke is considered a risk factor, there are other, more important risk factors in the substances formed during the combustion of tobacco such as carbon monooxide, tar products, aldehydes and hydrocyanic acid. It is now widely recognized that smoking can be a major health hazard. This hazard can be cut down by reducing or eliminating smoking, but smokers find this extremely difficult and it is generally accepted that this difficulty is caused by nicotine-dependence. While the presence of nicotine in tobacco smoke is considered a risk factor, there are other, more important risk factors in the substances formed during the combustion of tobacco such as carbon monooxide, tar products, aldehydes and hydrocyanic acid. One way of eliminating risk factors other than nicotine is disclosed in the U.S. Pat. No. 4,284,098. According to this patent pure nicotine vapors are obtained when air is drawn through a device containing a nicotine mixture disposed within an absorbent member. The nicotine mixture may be selected from the group consisting of nicotine (d), nicotine (l), nicotine (d,l), nicotine salts and nicotine esters. One way of eliminating risk factors other than nicotine is disclosed in the U.S. Pat. No. 4,284,098. According to this patent pure nicotine vapors are obtained when air is drawn through a device containing a nicotine mixture disposed within an absorbent member. The nicotine mixture may be selected from the group consisting of nicotine (d), nicotine (l), nicotine (d,l), nicotine salts and nicotine esters. Web site: http://www.delphion.com/details?pn=US04907606__
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Tobacco with reduced nicotine content due to microbial treatment Inventor(s): Newton; Richard P. (Louisville, KY), Jewell; John N. (Floyd Knobs, IN), Geiss; Vernon L. (Floyd Knobs, IN), Gravely; Lawrence E. (Louisville, KY) Assignee(s): Brown & Williamson Tobacco Corporation (Louisville, KY) Patent Number: 4,151,848 Date filed: April 13, 1977
454 Nicotine
Abstract: A process for the reduction of the nicotine content of tobacco by microbial treatment is disclosed. Tobacco is subjected, under controlled conditions, to the action of a microorganism effective to degrade nicotine through a biochemical reaction in which, inter alia, 3-succinoylpyridine is formed. Prior to subjecting the tobacco to the action of the microorganism, the tobacco is steamed to increase its moisture content. Tobaccos with lowered nicotine content but no mass loss result from this process following short treatment periods. Also, tobacco treated in accordance with this process, when incorporated into a tobacco smoking product, produces a mild smoke, having a reduced nicotine content. However, there is no loss of desirable flavor, taste and smoking properties. Excerpt(s): The present invention pertains to a process of reducing the nicotine content of tobacco by treating the tobacco with cultures of microorganisms. More specifically, the present invention pertains to an improved process for treating tobacco by subjecting it to the action of particular microorganisms, under controlled conditions, whereby the nicotine content of the tobacco is reduced in a relatively short time. The process is effective to reduce the nicotine content of tobacco without substantially reducing the perceived strength of smoke generated by smoking articles produced from the tobacco. However, there is a reduction in irritating properties of smoke which is generated from tobacco treated by the process of the present invention. For various reasons, it is often desirable to reduce the nicotine content of tobacco. For example, in recent years, low nicotine content "mild" cigarettes have gained substantial consumer acceptance. There are numerous techniques available for reducing the nicotine content of tobacco. However, most of these techniques result in the removal of other tobacco ingredients along with the nicotine. The removal of other ingredients adversely affects desirable flavor and taste properties, or other desirable smoking qualities. Thus, there is a need for techniques which are effective to selectively reduce the nicotine content of tobacco without deleteriously modifying its desirable smoking properties. Web site: http://www.delphion.com/details?pn=US04151848__ •
Transcutaneous application of nicotine Inventor(s): Etscorn; Frank T. (121 Stallion Cir., Socorro, NM 87801) Assignee(s): none reported Patent Number: 4,597,961 Date filed: January 23, 1985 Abstract: Percutaneous administration of nicotine in a dose approximating the dose delivered by a variety of nicotine-containing products, such as cigarettes, cigars, snuff and chewing tobacco, is carried out using an occlusive pad. The nicotine is delivered so as to mimic the pharmacological effects of nicotine provided by the conventional use of tobacco, and a therapeutic function is achieved by reducing or eliminating the need for the tobacco product. A suitable transdermal application pad comprises a reservoir for liquid nicotine base to be affixed to the skin in a variety of places. Due to the high lipid solubility and resultant high skin permeability of nicotine, vehicles or solvents are not generally needed to enhance dermal absorption. Excerpt(s): The present invention relates to the cutaneous administration of nicotine, and more especially to a new method of administering nicotine through the skin using a transdermal delivery system, especially for the purpose of satisfying a nicotine habit while minimizing or eliminating side effects caused by absorbing tobacco constituents
Patents 455
through the lungs along with products of combustion of tobacco. The health hazards from tobacco smoking are well established. Of the approximately 4,000 by-products of combustion found in cigarette smoke, many of which are known carcinogens, the three substances studied most have been tars, carbon monoxide and nicotine. Tars and carbon monoxide hae been directly implicated in the production or exacerbation of numerous health disorders. Thus, tars are the causitive agents in cigarette smoke most implicated in the induction of such cancers as lung, larynx, oral cavity, esophageal, bladder, kidney, pancreatic stomach, and uterine and cervix cancers. Tars are also considered responsible for the induction of the hepatic microsomal ensyme systems which result in more rapid deactivation of a variety of drugs such as benzodiazepines as well as anti-depressants and analgesics. Tars are also responsible for the production of bronco pulmonary diseases, including pulmonary emphysema, chronic bronchitis and smokers respiratory syndrome. Web site: http://www.delphion.com/details?pn=US04597961__ •
Transdermal nicotine delivery system Inventor(s): Yeh; Sharlin E. (Randolph, NJ), Patel; Niranjan (Dover, NJ), Milstone; Josephine (Ridgefield Park, NJ) Assignee(s): Warner-Lambert Company (Morris Plains, NJ) Patent Number: 5,230,896 Date filed: October 12, 1989 Abstract: A novel transdermal delivery system for nicotine to satisfy addicted smokers' cravings therefore is comprised of a nicotine base, an acrylate polymer adhesive, a stabilizer and a polyester film backing. The nicotine is absorbed through the skin at sufficiently high levels to reduce or eliminate the desire to smoke, yet its concentration within the acrylate matrix is such that a laminar patch is constructed that is neither bulky nor obvious when worn. A method of manufacture of the transdermal system is also described. Excerpt(s): Perhaps some of the most important medical issues for years has been the health risks associated with cigarette smoking such as lung cancer, heart disease and emphysema, just to name a few. Moreover, new medical evidence regarding the dangers of exposure to second hand smoke by non-smokers has resulted in a societal conflict between the rights of smokers and those of the non-smoker. Despite attempts by many smokers to quit for both health reasons and peer pressure, their addiction to the nicotine element of cigarette smoke prevents their doing so as they have become both physiologically and psychologically dependant. Hence, numerous products have been developed in the past to administer nicotine in a manner other than cigarette smoke so as to cure the craving while at the same time avoiding the deleterious effects of tars and carbon monoxide, inherent components of cigarette smoke. Nicotine containing pills have been developed, see U.S. Pat. No. 3,368,567 to Speer, however these have failed to successfully quell the nicotine craving since they are unable to achieve effectively high nicotine blood levels. A drug such as nicotine that is administered orally and absorbed by the stomach must first pass through the liver where most of it is deactivated. Nicotine-containing chewing gum encounters much of the same deactivation problems although some have found modest market success such as Nicorette.RTM., Lakeside Pharmaceuticals, Cincinnati, Ohio. These have also raised concerns regarding the causation of gum disease and their less than pleasant taste also affects patient compliance. The object of the present invention is to provide a means, both economically
456 Nicotine
and conveniently, for the administration of nicotine to the bloodstream of an addicted cigarette smoker by a means that will both avoid nicotine deactivation by the liver and will result in nicotine blood concentrations that will sufficiently satisfy the cravings of even the most ardent nicotine-dependant cigarette smoker. It is a further object of the present invention to provide a small, thin layered patch for the transdermal administration of nicotine to the blood stream in amounts sufficiently high enough to quell any craving for the drug so as to lessen or avoid any psychological or physiological discomfort by the addicted cigarette smoker. It is a further object of the present invention to provide a transdermal delivery system for nicotine composed of thin layered patches containing a range of concentrations of nicotine contained therein so that a gradual withdrawal from the substance can occur over time resulting in an eventually complete elimination of the addiction. Finally, it is an object of the present invention to provide a thin layered transdermal patch that can be discretely worn by the addict and yet contain sufficiently high concentrations of nicotine so as to be effective in reducing the addict's craving therefore. Web site: http://www.delphion.com/details?pn=US05230896__ •
Transdermal nicotine metabolites and human body weight Inventor(s): Keenan; Robert M. (Baltimore, MD) Assignee(s): Pharmaco Behavioral Associates, Inc. (Towson, MD) Patent Number: 5,972,974 Date filed: November 7, 1996 Abstract: A therapeutic method is provided to manage human body weight in nicotineexperienced or nicotine-naive individuals, comprising of transdermally administering an amount of nicotine metabolites or a pharmaceutically acceptable salts thereof to a human in need of such treatment, in an amount which is effective to manage human body weight. Excerpt(s): The invention relates to the therapeutic methods and articles of manufacture to alleviate the tobacco withdrawal syndrome or manage human body weight with the use of nicotine metabolites or pharmaceutically acceptable salts thereof. The invention includes methods and articles of manufacture using nicotine metabolites or pharmaceutically acceptable salts thereof to alleviate symptoms of nicotine withdrawal and craving associated with cessation of tobacco or nicotine use, as well as the management of human body weight in nicotine-experienced or nicotine-naive humans. Cigarette smoking continues to be the major preventable cause of death in the United States resulting in nearly 400,000 deaths per year due to cancer and cardiovascular disease. Despite the potential adverse health effects, the vast majority of cigarette smokers are unable to cease smoking. The lack of smoking cessation success is thought to be related to the tobacco withdrawal syndrome or tobacco abstinence syndrome that most smokers experience during their attempts to quit. See, Office of Smoking and Health, The Health Consequences of Smoking: Nicotine Addiction. A Report to the Surgeon General, U.S. Govt. Print. Off., Washington D.C., DHHS Pub. No. (CDC) 888406 (1988). The most common effects are similar to those in almost all abstinence syndromes, and include decreased heart rate, anxiety, tension, difficulty concentrating, impatience, depression, increased appetite with accompanied weight gain, irritability and restlessness. See, American Psychiatric Assoc., Diagnostic and Statistical Manual, Washington D.C. (3rd ed. 1980) at pages 159-160, 176-178. Most withdrawal effects occur within 24 hours, peak in the first 1-2 weeks and significantly decrease at one month. It is
Patents 457
widely believed that the effects of abstinence from tobacco are due to nicotine deprivation, and that abstinence effects from smoking prevent smokers from stopping. See, J. R. Hughes et al., in Research and Advances in Alcohol and Drug Problems, Vol. 10, L. T. Kozlowski et al., eds., Plenum Pub. Corp. (1990) at pages 317-398. The relationship between tobacco use and decreased body weight has been known for more than 100 years. It has been well established that smokers weigh less than non-smokers. Recent research has shown that nicotine is the substance responsible for the decreased body weight of tobacco users (See, Chapter on Nicotine Dependence, The National Institute On Drug Abuse's Fourth Triennial Report to Congress, In Press). Two major factors related to nicotine use cessation are responsible for weight gain in the posttobacco cessation period including 1) decreased metabolism and/or 2) increased dietary intake. Conversely, it must be the case that nicotine use results in increased metabolism and/or decreased dietary intake. Web site: http://www.delphion.com/details?pn=US05972974__ •
Treatment and system for nicotine withdrawal Inventor(s): Reynolds; Mark (4 Sidehill Rd., Westport, CT 06880) Assignee(s): none reported Patent Number: 6,409,991 Date filed: December 15, 1999 Abstract: A kit and associated method in which symptoms of nicotine withdrawal syndrome are relieved as well as addressing the associated weight gain issues and craving for sweets by combining nicotine replacement therapy with complementary dosages of xylitol. Excerpt(s): The present invention relates to a method for relieving nicotine addiction and in particular to a kit and associated method in which symptoms of nicotine withdrawal syndrome are relieved while addressing the associated oral cravings for sweets. Cigarette smoking continues to be the major preventable cause of death in the United States resulting in nearly 400,000 deaths per year due to cancer and cardiovascular disease. Despite the potential adverse health effects, the vast majority of cigarette smokers are unable to cease smoking. The lack of smoking cessation success is thought to be related to the tobacco withdrawal syndrome or tobacco abstinence syndrome that most smokers experience during their attempts to quit. As many as one third of heavy smokers who are now 35 years old will die before age 85 of diseases caused by their smoking. The estimated cost of health problems associated with smoking, including medical care, absenteeism, decreased work productivity, and accidents is estimated to be $56 billion per year. Web site: http://www.delphion.com/details?pn=US06409991__
•
Treatment of nicotine craving and/or smoking withdrawal symptoms Inventor(s): Majeti; Satyanarayana (Cincinnati, OH) Assignee(s): The Procter & Gamble Company (Cincinnati, OH) Patent Number: 5,599,554 Date filed: March 19, 1996
458 Nicotine
Abstract: The subject invention encompasses a transdermally or transmucosally administrable composition for the treatment or nicotine craving or smoking withdrawal symptoms comprising nicotine and caffeine or caffeine equivalent. Excerpt(s): The health hazards from smoking tobacco are well known. Of the many byproducts of combustion found in cigarette smoke, the substances most studied have been tars, carbon monoxide, and nicotine. Tars are the agents linked to the causation of various cancers and pulmonary diseases such as emphysema and chronic bronchitis. Carbon monoxide is a deadly gas which reduces the ability of blood hemoglobin to carry sufficient oxygen. Carbon monoxide has also been causally linked to coronary artery disease and atherosclerosis. Nicotine appears to be the most pharmacologically active substance in tobacco smoke, yet it seems not to be as significant from a health standpoint as the tars and carbon monoxide. However, nicotine is the reinforcing substance in tobacco which maintains the addiction. Various efforts have been made by smokers to discontinue smoking. Chewing beeswax, eating candy and peppermints, as well as cold turkey interruption have been tried without much success. The addition of chemicals designed to sicken the user or otherwise render smoking repulsive to the user have also not produced good results. More recent therapies for smoking cessation have focused on the administration of nicotine to the smoker. These therapies allow the individual to satisfy a nicotine habit while minimizing or eliminating side effects caused by absorbing nicotine through the lungs along with the other harmful by-products of combustion of tobacco. Nicotine supplementation has proven to be an effective therapy as an adjunct to smoking cessation in helping to reduce the craving for smoking and provide relief from smoking withdrawal symptoms. However, there are many smokers for whom nicotine supplementation alone is inadequate. In accordance with the present invention, it has been discovered that a composition can be formulated which provides the combination of nicotine and caffeine or caffeine equivalent in a single therapy. It has also been discovered that such a combination may offer the advantage of providing treatment and/or relief of nicotine craving and/or smoking withdrawal symptoms to a broader spectrum of smokers who wish to break the smoking habit. It has further been discovered that these compositions may also curb the appetite which may aid in reducing the weight gain that is commonly experienced by individuals who stop smoking. Web site: http://www.delphion.com/details?pn=US05599554__ •
Treatment of tobacco to reduce tar and nicotine content Inventor(s): Drazic; Nikola (38 Evenlea Walk, Winnipeg, Manitoba, CA) Assignee(s): none reported Patent Number: 4,819,667 Date filed: July 31, 1987 Abstract: The tar and nicotine content of tobacco is reduced by passing through the tobacco a combination of steam and starch cells. Excerpt(s): This invention relates to a process for treating tobacco and particularly for the purposes of reducing the content therein of nicotine and tar for use of the tobacco in smoking materials. The use of tobacco particularly in smoking materials has received much condemnation from health authorities on the grounds that particularly the tar and nicotine content can be injurious to the health of the smoker or to those around the smoker. Over the years therefore the tobacco industry have attempted to reduce the
Patents 459
amount of tar and nicotine passing from the cigarette or other smoking material to the user generally by providing filters of different types to extract the unwanted materials. Generally however there has been no reduction of the amount of tar or nicotine in the actual smoking material itself and the filter has been relied upon to filter out the materials rather than to have them removed in a previous process. This technique is of course less satisfactory because the filter can only operate to a certain efficiency and also because much of the smoke does not in fact pass through the filter for example when the cigarette is merely burning in an ashtray. Web site: http://www.delphion.com/details?pn=US04819667__ •
Use of.alpha.-conotoxin MII to treat disorders resulting from nicotine-stimulated dopamine release Inventor(s): McIntosh; J. Michael (Salt Lake City, UT), Kulak; Jennifer M. (Salt Lake City, UT), Yoshikami; Doju (Salt Lake City, UT), Olivera; Baldomero M. (Salt Lake City, UT) Assignee(s): University of Utah Research Foundation (Salt Lake City, UT) Patent Number: 5,929,034 Date filed: March 23, 1998 Abstract: Neuronal nicotinic acetylcholine receptors (nAChRs) are believed to mediate nicotine addiction. In addition, stimulation of nAChRs modulates release of neurotransmitters including dopamine, norepinephrine and serotonin. Thus, pharmacological manipulation of nicotinic receptors has implications for a wide variety of disorders including psychotic, mood, movement and cognitive. For most nAChRs, there are no subtype selective ligands. However,.alpha.-conotoxin MII, a small peptide from the carnivorous marine snail Conus magus, was recently isolated. This peptide has been shown to be a specific antagonist for.alpha.3.beta.2 nicotinic receptors. The peptide potently blocks part, but not all, of nicotine-stimulated dopamine release from rat brain striatal synaptosomes. In contrast it has no effect on potassium stimulated dopamine release. Other.alpha.-conotoxins specifically target distinct neuronal nAChR subtypes.alpha.-Conotoxins thus represent new lead compounds for CNS disorders. Excerpt(s): The present invention relates to the use of the.alpha.-conotoxin MII to treat disorders that are caused by the action of nicotine stimulating nicotinic acetylcholine receptors (nAChRs). When nicotine binds to certain subtypes of nAChRs it induces the release of dopamine. The.alpha.-conotoxin MII has now been found to be a specific neuronal nAChR antagonist and can limit nicotine stimulated dopamine release. Cigarette smoke contains nicotine, which acts upon nAChRs resulting in dopamine release, which is effectively a reward. Treatment with.alpha.-conotoxin MII will block the nicotinic receptors thereby preventing the release of dopamine and will block the reward. Consequently.alpha.-conotoxin MII can be used to aid persons to quit smoking. A second aspect of the invention is that.alpha.-conotoxin MII is useful for the treatment of various psychoses, e.g., schizophrenia and mood disorders. Presently the standard treatment for psychosis is to block the post-synaptic dopamine recognition. The equivalent effect is be achieved by blocking an earlier step, specifically, by blocking the presynaptic release of dopamine.alpha.-Conotoxin MII is effective at preventing the presynaptic release of dopamine because it is a nAChR antagonist. The publications and other materials used herein to illuminate the background of the invention, or to provide additional details respecting the practice, are incorporated by reference and for convenience are respectively grouped in the appended List of References.
460 Nicotine
Web site: http://www.delphion.com/details?pn=US05929034__ •
Wetted impact barrier for the reduction of tar and nicotine in cigarette smoke Inventor(s): Rosen; William E. (2055 Wisteria La., Lafayette Hill, PA 19444), Rosen; William E. (2055 Wisteria La., Lafayette Hill, PA 19444), Rosen; David I. (2055 Wisteria La., Lafayette Hill, PA 19444), Rosen; David I. (2055 Wisteria La., Lafayette Hill, PA 19444), Rosen; Adam H. (2055 Wisteria La., Lafayette Hill, PA 19444), Rosen; Adam H. (2055 Wisteria La., Lafayette Hill, PA 19444) Assignee(s): none reported, none reported Patent Number: 5,240,015 Date filed: February 14, 1991 Abstract: This invention is devised to be a free standing wetted impact barrier for dispensing onto a cigarette. Only when applied on the top mouthpiece of cigarette filter types does it become a part of the filter. More particularly, this invention relates to a wetted impact barrier kit which includes a free standing wetted barrier placed in a container with a dispenser and an instruction sheet on how to use the kit. The wetted impact barrier is dispensed on the top end surface of cigarette filter type mouthpiece, to reduce tar and nicotine of cigarettes (total particular matter), when smoked. This invention is designed only to dispense the wetted impact barrier on the top end surface of a mouthpiece of a cigarette filter The wetted impact barrier helps to eliminate or remove the primary tars and nicotine and certain other volatiles from cigarette smoke. Excerpt(s): This invention relates to the tobacco art, and more particularly, to a wetted impact barrier which is separate and in no way attached or bound to cigarette filter types until the wetted impact barrier is physically applied to create a wetted impact barrier to the top end surface of cigarette filter mouthpiece where the smoke is drawn through the mouth. Also included is a kit and method of application of said kit to a cigarette in order to reduce the tar and nicotine inhaled by the cigarette smoker. The kit comprising a dispenser with instructions. This invention relates to the tobacco art, and more particularly, to a wetted impact barrier which is separate and in no way attached or bound to cigarette filter types until the wetted impact barrier is physically applied to create a wetted impact barrier to the top end surface of cigarette filter mouthpiece where the smoke is drawn through the mouth. Also included is a kit and method of application of said kit to a cigarette in order to reduce the tar and nicotine inhaled by the cigarette smoker. The kit comprising a dispenser with instructions. There have been attempts to design tar and nicotine reducing elements for tobacco smoke described in the prior art and several of these elements contain means for moistening or humidifying a porous filter. Typically, a frangible module containing water or an aqueous solution is embedded in the filter and the module is compressed to release the liquid before the filter is used. The moistened filter material in the element then exhibits an improved ability to remove the primary tars, nicotine, and certain other volatiles from the smoke. There have been attempts to design tar and nicotine reducing elements for tobacco smoke described in the prior art and several of these elements contain means for moistening or humidifying a porous filter. Typically, a frangible module containing water or an aqueous solution is embedded in the filter and the module is compressed to release the liquid before the filter is used. The moistened filter material in the element then exhibits an improved ability to remove the primary tars, nicotine, and certain other volatiles from the smoke. For example, in U.S. Pat. No. 3,884,246, to Eric E. Walker, a tobacco smoke filter element comprised of a resilient, water impervious elongated
Patents 461
tubular casing having a porous plug of filtering material disposed in each end of said casing; opposed, mutually spaced, disc-like walls disposed within said casing between said plugs, one wall within said casing between said plugs and one wall abutting the inner surface of each plug, said walls defining a chamber within the central portion of said casing and having at least one port in each wall. The device further including at least one liquid containing module disposed within said chamber and extending between said walls, wherein said walls have at least one passage for allowing smoke through said filter element and means carried by said element and cooperating between said module and at least one port in each of said walls for directing liquid from said module through the ports into said plugs responsive to compression of the external walls of said chamber so that said plugs may act selectively as a dry filter, or when said casing is compressed, as a filter moistened by said liquid. For example, in U.S. Pat. No. 3,884,246, to Eric E. Walker, a tobacco smoke filter element comprised of a resilient, water impervious elongated tubular casing having a porous plug of filtering material disposed in each end of said casing; opposed, mutually spaced, disc-like walls disposed within said casing between said plugs, one wall within said casing between said plugs and one wall abutting the inner surface of each plug, said walls defining a chamber within the central portion of said casing and having at least one port in each wall. The device further including at least one liquid containing module disposed within said chamber and extending between said walls, wherein said walls have at least one passage for allowing smoke through said filter element and means carried by said element and cooperating between said module and at least one port in each of said walls for directing liquid from said module through the ports into said plugs responsive to compression of the external walls of said chamber so that said plugs may act selectively as a dry filter, or when said casing is compressed, as a filter moistened by said liquid. Web site: http://www.delphion.com/details?pn=US05240015__
Patent Applications on Nicotine As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to nicotine: •
Anhydrous purification of nicotine using an ion exchange resin Inventor(s): Hughes, Lyn; (Harleysville, PA) Correspondence: ROHM AND HAAS COMPANY; PATENT DEPARTMENT; 100 INDEPENDENCE MALL WEST; PHILADELPHIA; PA; 19106-2399; US Patent Application Number: 20020016469 Date filed: June 20, 2001 Abstract: An improved process for producing high purity nicotine. The process involves passing a solution of less pure nicotine in a non aqueous solvent through a cation exchange resin such that the color is retained on the resin, and the nicotine passes through. The process eliminates the need for distillation to separate the nicotine from the color-causing compounds. The solvent used in the process is a fluorinated
10
This has been a common practice outside the United States prior to December 2000.
462 Nicotine
hydrocarbon that is quantitatively recovered and re-used. It is non-flammable, nonozone depleting, and has low toxicity. Excerpt(s): The present invention relates to the anhydrous purification of nicotine using cation exchange resins. Nicotine is a naturally occurring alkaloid that is found in the tobacco plant, Nicotiana tobacum. It finds great use in the pharmaceutical and agricultural industries. In the pharmaceutical industry it is extensively used in smoking cessation formulations. In this use the nicotine can be administered in the form of lozenges, chewing gum, and inhalers. Because these applications are for human ingestion it is required that the nicotine be of very high purity as defined in the US Pharmacopeia. In agriculture it is used as a pesticide and is usually formulated as the nicotine sulfate salt dissolved in water. The common concentration is 40% nicotine. When used as a pesticide it is not necessary to meet the same stringent purity requirements as for pharmaceutical use. Typically, nicotine is produced by extraction from tobacco leaves or waste products from the manufacture of tobacco for smoking. This extraction has been achieved both by extraction with organic solvents and aqueous solvents. The extraction is followed by multiple purification steps. These steps can include liquid-liquid extraction, chromatography, distillation, and ion exchange absorption/elution. For the production of high purity nicotine the final steps include vacuum distillation. The primary purpose of the distillation is to separate the nicotine from colored impurities. It also serves to reduce the water content. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Bridged nicotine compounds for use in the treatment of CNS pathologies Inventor(s): Crooks, Peter A. (Lexington, KY), Grinevich, Vladimir P. (Lexington, KY), Dwoskin, Linda P. (Lexington, KY), Xu, Rui; (Longmont, CO) Correspondence: MCDERMOTT WILL & EMERY; 600 13TH STREET, N.W. WASHINGTON; DC; 20005-3096; US Patent Application Number: 20020099069 Date filed: August 30, 2001 Abstract: Pharmaceutical compounds comprising bridged nicotine analogs of Noctylnicotinium iodide (NONI) having selective antagonist properties at.alpha.3.beta.2containing nicotinic receptor subtypes, and compositions containing these compounds. The compounds and compositions are used to treat central nervous system pathologies. Excerpt(s): This invention relates to bridged nicotine analogs of N-octylnicotinium iodide (NONI) that have selective antagonist properties at.alpha.3.beta.2-containing nicotinic receptor subtypes and to a method of using such compounds to treat central nervous system pathologies. The present invention also relates to pharmaceutical compositions containing these compounds, as well as various uses thereof. Formula (I) below shows the structure of S-(-)-nicotine (NIC), which activates neuronal nicotinic receptors evoking release of dopamine (DA) from presynaptic terminals in the central nervous system (CNS). NIC is a legal substance of dependence that produces many of its effects on the CNS, some of which may be considered to be beneficial, e.g., mood elevation, arousal and learning and memory enhancement. NIC produces its effect by binding to a family of ligand-gated ion channels, stimulation by acetylcholine (ACh) or NIC causes the ion channel to open, and cations to flux with a resulting rapid (in msec) depolarization of the target cell. Over the last 12 years, there has been a substantial increase in studies on brain nicotinic receptors. These nicotinic receptors are composed
Patents 463
of four subunit domains: 2.alpha.,.beta.,.gamma. and.delta. or.epsilon. Neuronal nicotinic receptors are composed of only two subunits,.alpha. and.beta. and are believed to assemble with the general stoichiometry of 2.alpha. and 3.beta. Eight subtypes of the cc subunit (.alpha.2 to.alpha.9) and three subtypes of the.beta. unit (.beta.2 to.beta.4) are found in CNS. The most common nicotinic receptor species in the brain is composed of two.alpha.4 and three.beta.2 subunits, i.e.,.alpha.4.beta.2. These subunits display different, but overlapping, patterns of expression in the brain. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Chewing gum composition for eliminating nicotine Inventor(s): Roh, Hoe Jin; (Seoul, KR), Lee, Ki Jeong; (Gyeonggi-do, KR), Choi, Jin Hwan; (Seoul, KR), Park, Cheon Ho; (Gyeonggi-do, KR), Rha, Chan Su; (Seoul, KR) Correspondence: Ronald L. Grudziecki; BURNS, DOANE, SWECKER & MATHIS, L.L.P. P.O. Box 1404; Alexandria; VA; 22313-1404; US Patent Application Number: 20030129145 Date filed: August 21, 2002 Abstract: Disclosed is a chewing gum composition capable of eliminating nicotine component from the body of a person chewing the chewing gum. Such a chewing gum composition functions to convert the nicotine produced in a human body after smoking to cotinine and to discharge the cotinine into urine. Accordingly, by chewing the chewing gum of the present invention, not only nicotine can be eliminated from the body, but also the incidence of cancer due to nicotine can be largely reduced. Excerpt(s): The present invention relates to a chewing gum composition for eliminating nicotine, and more particularly to such a composition capable of eliminating the nicotine component from the body of a person chewing the chewing gum. Nicotine is known as a toxic material contained in large quantities in tobacco, which stimulates or paralyzes the central nervous system and peripheral nerves and contracts blood vessels. In particular, N-nitrosamine, a metabolic product of nicotine is known as a strong carcinogen (Eugene et al., Carcinogenesis, 20: 133-137, 1999) and carcinogenic activities have been reported in about 200 kinds of N-nitrosamines until recently. Besides N-nitrosamine, cotinine, another metabolic product of nicotine, and keto acid and hydroxy acid, other metabolic products of nicotine can act as competitive inhibitors which disturb the conversion path of nicotine to carcinogenic N-nitrosamine by aid of cytochrome P.sub.450, an enzyme existing in the liver and the like. If, therefore, the conversion path of nicotine to cotinine can be activated so as to increase the production of cotinine and simultaneously an activity of enzyme participating in the production of nitrosamine can be inhibited, nicotine accumulated in a human body by smoking can be effectively eliminated and thus cancer due to nicotine will be prevented. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
464 Nicotine
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Coffee having a nicotine composition dissolved therein Inventor(s): Fortune, Stephen JR. (Bridgewater, MA) Correspondence: WOLF GREENFIELD & SACKS, PC; FEDERAL RESERVE PLAZA; 600 ATLANTIC AVENUE; BOSTON; MA; 02210-2211; US Patent Application Number: 20020009533 Date filed: May 17, 2001 Abstract: The present invention relates, in part, to a nicotine-containing composition that can be readily dissolved in a beverage such as coffee. The composition comprises nicotine as an active ingredient, a water-soluble filler, and in some instances, a binder. The composition can be provided as a tablet or a powder and is capable of dissolving in the beverage within a very short period of time. The present invention also relates, in part, to a method for preparing a beverage comprising nicotine. The present invention also encompasses compositions comprising coffee and nicotine including nicotinecoated coffee beans, or a packet containing compositions comprising desired amounts of coffee and nicotine. Excerpt(s): This non-provisional application claims the benefit under Title 35, U.S.C.sctn.119(e) of co-pending U.S. provisional application serial no. 60/204,937 filed May 17, 2000, incorporated herein by reference. The present invention relates to nicotine or a nicotine-containing composition for ingestion with a beverage, such as coffee. In many states and countries, there exists a ban on smoking in public premises. Accordingly, a person who wishes to smoke must step outside the premises. The option of leaving the premises, however, is not present for other public places, in particular, public modes of transportation such as buses, trains or airplanes. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
•
Dextrorotary nicotine for smoking cessation Inventor(s): Gorenstein, Leonard; (Port Richey, FL) Correspondence: SMITH & HOPEN PA; 15950 BAY VISTA DRIVE; SUITE 220; CLEARWATER; FL; 33760 Patent Application Number: 20030082109 Date filed: October 30, 2001 Abstract: The present invention provides a substitute for smoking which includes, in a first embodiment, a conventional chewing gum base comprising about 40 percent, by weight, of the substitute and an amount of synthetic dextrorotary isomer of nicotine, which is only half as toxic as tobacco-derived laboratory nicotine, in a range of about 0.02 to 8.0 percent by weight relative to the chewing gum base, each piece or dosage containing an amount of the isomer of nicotine in a range of about 0.5 to 40 milligrams. A kit has a plurality of dosages covering the percent weight range of 0.02 to 8.0 and amount range of 0.5 to 40 milligrams, enabling a person to consume progressively smaller amounts of the isomer to gradually overcome an addiction to smoking. Additional embodiments include base materials other than chewing gum. Excerpt(s): The present invention relates to the field of chewable or edible substitutes for smoking, and particularly for such substitutes adapted for enabling a gradual withdrawal from dependency or addiction to smoking. Smoking tobacco products, whether in the form of cigarettes, cigars, or pipes, are detrimental and hazardous to a
Patents 465
person's health. Numerous well-publicized studies have indicated that the incidence or risks of lung cancer, emphysema and heart problems is significantly higher in heavy smokers than in non-smokers, and that the incidence and effects increase with the extent of smoking. Many studies also indicate, if the diseases have not yet started, or some are not far advanced, that much of the risk can be eliminated by stopping or drastically curbing the smoking habit. In spite of the apparent conclusiveness of such studies, a large percentage of the population continues to smoke. Many persons who do smoke recognize those inherent risks but feel the present satisfactions gained by smoking outweigh possible future bad effects or find that they are addicted to smoking to the extent they are unable to stop. Many who do stop smoking start smoking again, for the reasons just mentioned. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Edible herbal compositions for relieving nicotine craving Inventor(s): Jacob, Peyton III; (Lafayette, CA), Shulgin, Alexander T. (Lafayette, CA), Wolfson, Philip; (San Anselmo, CA) Correspondence: Richard C. Litman; Litman Law Offices, Ltd. P.O. Box 15035; Crystal City Station; Arlington; VA; 22215-0035; US Patent Application Number: 20020025300 Date filed: June 4, 2001 Abstract: Compositions useful in relieving craving in nicotine habituated patients are provided that include an herbal component. The herbal component provides multiple nicotine agonists, one of which is anabasine. The compositions are preferably in the form of chewing gum, tablets, capsules, or lozenge. Excerpt(s): This application claims the benefit of U.S. Provisional Patent Application Serial No. 60/209,028, filed Jun. 2, 2000. The present invention generally relates to compositions useful in relieving craving in a nicotine habituated patient who is abstaining from or reducing nicotine intake, and more particularly relates to edible compositions including an herbal component which provides multiple nicotine agonists, one of which is anabasine, but has little or no nicotine. Using 1996 data, the prevalence of cigarette smoking in the United States among adults was about 27% or 55 million people. Each year some 30% of smokers try to quit, but only about 10% are successful. The efficacy rate for formal cessation programs, defined as abstinence at one year follow-up, is between 20 and 40% of those enrolled. The most telling fact is that the majority of smokers who are successful in quitting tobacco have done so on their own. In the past ten years, 47.5% of persons attempting to quit smoking on their own were successful compared to 23.6% of those who used smoking cessation programs to quit. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Element giving rapid release of nicotine for transmucosal administration Inventor(s): Wilhelmsen, Paul C. (Alamo, CA) Correspondence: PAUL C. WILHELMSEN; 5100 Channel Ave. Richmond; CA; 948044646; US Patent Application Number: 20010016593 Date filed: January 29, 2001 Abstract: An pharmacological element, generally configured in the shape of a tablet, for the transmucosal administration of nicotine is made to effect the equivalent physiological and psychological responses of smoking a cigarette. The element is made by placing between 0.5 mg and 5 mg of nicotine in a layer upon a non-nicotine containing matrix. The nicotine containing layer rapidly dissolves by the warmth and saliva in the mouth. The nicotine is then rapidly absorbed by the intra-oral mucosal surfaces of the mouth, and then felt as a sharp pulse in the brain in a period of less than two minutes, but usually in less than 30 seconds. A multi-layered element is also provided where the nicotine is placed in a plurality of layers separated by one or more layers that are essentially free of nicotine to support the nicotine containing layers, and, to provide a time delay between the sharp pulses produced by the nicotine containing layers. The multi-layered element effects the equivalent of taking several drags of a cigarette over a period of minutes with each nicotine-containing layer in the multilayered element effecting a pulse of nicotine similar to each drag on a cigarette. An additional benefit of enhanced mental acuity is disclosed for the nicotine elements. Excerpt(s): This is a Continuation-in-Part (CIP) of allowed U.S. application Ser. No. 09/292,045, filed Apr. 20, 1999. This application is not the subject of any federally sponsored research and development. The present invention relates to an element for transmucosal administration of a medicament. Specifically, it relates to an element that will give a rapid release of nicotine. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Hapten-carrier conjugates for treating and preventing nicotine addiction Inventor(s): Naso, Robert B. (Gaithersburg, MD), Fattom, Ali Ibrahim; (Rockville, MD), Ennifar, Sofiane; (Silver Spring, MD) Correspondence: FOLEY AND LARDNER; SUITE 500; 3000 K STREET NW; WASHINGTON; DC; 20007; US Patent Application Number: 20030165950 Date filed: December 30, 2002 Abstract: Novel hapten-carrier conjugates are capable of inducing the production of antibodies, in vivo, that specifically bind to nicotine. These conjugates comprise a nicotine hapten conjugated to an immunogenic carrier protein. The novel conjugates preserve the chirality of nicotine in its native (S)-(-) state, and have good stability properties. The conjugates are useful in formulating vaccines for active immunization, that are used to prevent and treat nicotine addiction. The antibodies raised in response to the nicotine hapten-carrier conjugate are used for passive immunization. These antibodies are administered for prevention and treatment of nicotine addiction. Excerpt(s): The present invention relates to treatment and prevention of nicotine addiction. In particular, the invention relates to novel hapten-carrier conjugates which
Patents 467
are capable of inducing the production of antibodies. Such antibodies are capable of specifically binding to nicotine. Furthermore, the present invention envisages preventing or treating nicotine addiction by administering a nicotine-carrier conjugate in a pharmaceutically-acceptable formulation. The present invention also contemplates using the antibodies raised in response to the hapten-carrier conjugate for the prevention and treatment of nicotine addiction. Smoking of cigarettes, cigars, and pipes is a prevalent problem in the United States and worldwide. Smoking tobacco and smokeless tobacco are rich in nicotine, which is a known addictive substance. Nicotine is an alkaloid derived from the tobacco plant that is responsible for smoking's psychoactive and addictive effects. Nicotine is formed of two rings linked together by a single bond: an aromatic six-membered ring (pyridine) and an aliphatic five-membered ring (pyrrolidine). The pyrrolidine is N-methylated and linked through its carbon-2 to the carbon-3 of pyridine. Thus, the carbon-2 is chiral, and there is virtually free rotation around the single bond linking the two rings. It has been established that the absolute configuration of carbon-2 is S. Thus, the natural configuration of nicotine is (S)-(-)nicotine. Nicotine use is widespread due to the easy availability of cigarettes, cigars, pipes and smokeless tobacco. According to the U.S. Department of Health and Human Services, cigarette smoking is the single leading cause of preventable death in the United States. See also McGinnis et al., J. Am. Med. Assoc., 270, 2207-2211 (1993). Exposure to second hand smoke also has been reported to have serious detrimental health effects, including exacerbation of asthma. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Intraoral delivery of nicotine for smoking cessation Inventor(s): Liang, Alfred; (Edison, NJ), Chen, Li-Lan H. (Edison, NJ) Correspondence: ALLEN BLOOM; C/O DECHERT; PRINCETON PIKE CORPORATION CENTER; P.O. BOX 5218; PRINCETON; NJ; 08543-5218; US Patent Application Number: 20030068376 Date filed: April 18, 2002 Abstract: Dosage forms of a nicotine delivery system are disclosed in which a mucoadhesive film, made up of one or more non-microbial hydrocolloid(s) and an effective dose of nicotine, dissolves when applied intraorally to release the nicotine which is absorbed through the oramucosae and directly reaches systemic circulation. Methods for preparing various versions of the dosage forms are disclosed. Methods to assist smoking cessation or provide substitutes for smoking by administrating the dosage form are also provided. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/285,404, filed Apr. 20, 2001; the disclosure of which is incorporated herein by reference as if set forth herein in its entirety. The present invention is directed to providing a safe and effective means for delivering nicotine to the blood plasma. It can serve as an aid for people trying to stop smoking cigarettes or as a substitute for cigarettes. Specifically, the invention describes the composition of water-soluble, dissolving intraoral film dosage forms and methods for their manufacture and use. Nicotine is a naturally occurring drug found in tobacco. It can be introduced into the body through many routes, including the smoking of cigarettes. Unfortunately, introducing nicotine into the body in this manner also introduces many other compounds, some of which are deposited onto the lungs and can cause adverse health effects. There is also risk to bystanders in the form of second-hand inhalation of cigarette
468 Nicotine
smoke which has also been shown to cause adverse health effects. Smoking has become increasingly disfavored in recent years and many restrictions have been placed on where an individual may smoke. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Medicated chewing gum delivery system for nicotine Inventor(s): Shiffman, Saul; (Pittsburgh, PA), Gitchell, Joe; (Chevy Chase, MD), Sasan, Aradhana; (Springfield, VA), Henningfield, Jack E. (Baltimore, MD), Pinney, John M. (Bethesda, MD), Cherukuri, Subraman R. (Vienna, VA), Malvestutto, Carlos D. (Silver Spring, MD), Cone, Edward J. (Severna Park, MD) Correspondence: Liniak, Berenato, Longacre & White, LLC; Ste. 240; 6550 Rock Spring Drive; Bethesda; MD; 20817; US Patent Application Number: 20020098264 Date filed: February 1, 2002 Abstract: A chewing gum delivery system has nicotine, gum base and a buffer system with an improved release rate for the nicotine. The resulting delivery system advantageously provides a convenient, reliable, practical, and relatively painless system for delivering an active. The delivery system is capable of delivering initial and second doses of a craving reduction active or other actives (e.g., nicotine), the combination of which rapidly reduces cravings, or provides some other pharmacological effect, and provides the pharmacological effect or protection from such cravings over a prolonged period of time beyond the initial dose. Notably, the delivery system is capable of rapidly achieving a pharmacologically effective concentration of the active (e.g., nicotine) in the bloodstream (e.g., within 5 minutes, or more desirably within 3 minutes, or in some cases, within 1-2 minutes), and is also capable of keeping the concentration of the active in the bloodstream at or near the pharmacologically effective concentration for at least 20 minutes after chewing of the delivery system begins, or more desirably about 30 minutes to about 50 minutes after chewing begins. Excerpt(s): The present invention relates to medication delivery systems, and more specifically to nicotine delivery systems, and particularly to a nicotine chewing gum delivery system that provides for an improved nicotine release profile over existing systems. Delivery systems containing actives for oral administration now include various chewing gum formulations. Chewing gums permit release of the active over time as the gum product is masticated, or chewed. The action of saliva on the gum further facilitates release of the active, as well as its subsequent absorption by the mucous membranes lining the mouth, throat, larynx and esophagus. A problem with many chewing gum formulations is that they fail to deliver an adequate dosage of medicament or active in the appropriate manner over the entire dosing interval. This results in insufficient active being absorbed into the bloodstream for effective therapeutic or pharmacological actions. There are many reasons for inadequate dosing. Many chewing gum formulations release active medication slowly over time in a more or less continuous fashion. These formulations may also retain a significant portion of the active during the prescribed dosing period, resulting in inadequate dosing of the patient. Further, the particular gum base material chosen to contain and subsequently release the active material may not perform optimally. The gum base may be difficult to chew or unusually hard, thereby damaging the teeth and gums. The art has not suggested the appropriate gum base formulation, as well as other non-actives, which can be most successfully utilized in combination with a particular type of active. It has
Patents 469
therefore proven quite elusive to find the right qualitative and quantitative parameters for both actives and non-actives in the delivery system which will ensure a reliable release rate for the active substance. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method for reducing the effect of nicotine addiction and dependancy Inventor(s): Miller, Alcinda; (North Las Vegas, NV), Wastchak, David; (Tempe, AZ) Correspondence: Charles Hartman; P.O. Box 926; Reno; NV; 89505; US Patent Application Number: 20020078969 Date filed: December 21, 2000 Abstract: The nicotine addiction associated with smoking can be reduced by a combination of nutrition augmentation, craving reduction, and therapy. The craving reduction is accomplished by administration of corticotrophins and mild relaxants, for example, tryptophan and GABA precursors. Excerpt(s): This invention relates to methods to reduce the desire to smoke, in particular this invention relates to methods to quit smoking, and most particularly, this invention relates to methods to reduce the craving for nicotine after quitting smoking. Smoking is a huge health problem in the United States, and around the world. For example, every year cigarettes kill more Americans than AIDS, alcohol, car accidents, fires, illegal drugs, murder and suicide combined. Having said this, it is known that smoking is a notoriously hard habit to quit. That is because the smoker is addicted to nicotine, that is to say, the biochemistry of his or her body has become chemically dependant on nicotine, the primary alkaloid found in tobacco. It has been said that the chemical dependance formed by nicotine use can be harder to end than that caused by heroin or cocaine. Indeed, reliance on this chemical dependancy seems to have been one of the tobacco companies main marketing strategies for selling cigarettes and other forms of tobacco. Of course stopping smoking is one of the single most beneficial life style changes a smoker can do to improve health and increase longevity. It is known that smoking decreases lung capacity and function and is known to cause emphysema and has been implicated in many forms of cancer. It also is harmful to the gums, many other organs of the body, and, most notably, the skin--it causes deep wrinkling. This is in addition to administering to the smoker a large dose of carbon monoxide and other toxins which have a cumulative detrimental effect on the smokers over all health. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Method for the anhydrous loading of nicotine onto ion exchange resins Inventor(s): Hughes, Lyn; (Harleysville, PA), Bellamy, Simon Andrew; (Redhill, GB) Correspondence: Joanne P. Will; Rohm and Haas Company; Patent Department; 100 Independence Mall West; Philadelphia; PA; 19106-2399; US Patent Application Number: 20020015687 Date filed: June 20, 2001 Abstract: An environmentally friendly method of loading nicotine onto cation exchange resins under anhydrous conditions is described. The method eliminates many of the processing problems that are associated with loading in aqueous media.
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Excerpt(s): The present invention relates to a method for the loading of nicotine onto cation exchange resins under anhydrous conditions. Nicotine is a naturally occurring alkaloid that is found in the tobacco plant, Nicotiana tobacum. It finds great use in the pharmaceutical and agricultural industries. In the pharmaceutical industry it is extensively used in smoking cessation formulations. In this use the nicotine can be administered in the form of lozenges, chewing gum, and inhalers. When nicotine is formulated into chewing gum and lozenges it is first loaded onto a cation exchange resin which has the effect of controlling the release rate of the nicotine during chewing or sucking in the mouth. Such complexes of nicotine with ion exchange resins are the subject of GB1325011. In agriculture it is used as a pesticide; and it is formulated as the nicotine sulfate salt in water, at a 40% concentration. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method for treating nicotine addiction and deterring tobacco use with hypericum perforatum Inventor(s): Rosenthal, Norman E. (Rockville, MD), Friedman, Richard A. (New York, NY) Correspondence: SHANKS & HERBERT; Transpotomac Plaza; 1033 N. Fairfax St., Suite 306; Alexandria; VA; 22314; US Patent Application Number: 20010036486 Date filed: April 20, 2001 Abstract: A method of treating nicotine addiction or deterring tobacco use in a subject by administering to the subject a therapeutically effective amount of Hypericum perforatum or at least one active component thereof is disclosed. As disclosed, the composition may further comprise a pharmaceutically acceptable carrier. The composition may also comprise a supplementary compound such as L-phenylalanine, L-tyrosine, tryptophan, 5-hydroxy tryptamine, serotonin, calcium carbonate and magnesium oxide, kava-kava, a kava alkaloid, valerian, hops, a passion flower extract, vitamin C, or Echinacea. Excerpt(s): This application claims the benefit of U.S. Provisional Patent Application No. 60/202,823, filed May 8, 2000, naming Norman E. Rosenthal, and Richard Friedman, which is herein incorporated by reference. The invention relates to a method of deterring, tobacco use, ending tobacco use, treating nicotine addiction, or a combination thereof in a subject by administering to the subject a composition comprising a therapeutically effective amount of Hypericum perforatum, or at least one active component thereof or both. Tobacco use is the number one source of preventable death, primarily due to cardiovascular disease and cancer, in the United States. Approximately one-half of the 50 million smokers try to quit each year, but only about 6% of those who attempt to quit succeed in the long term. See MMWR Morb Mortal Wkly Rep (1993) 42:504-507. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
Patents 471
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METHOD OF INDIVIDUALS
ESTIMATING
RATE
OF
NICOTINE
METABOLISM
IN
Inventor(s): HORST, W. DALE; (NEWTON, KS) Correspondence: JOHN WERESH; SHOOK HARDY & BACON; ONE KANSAS CITY PLACE; 1200 MAIN STREET; KANSAS CITY; MO; 641052118 Patent Application Number: 20010039054 Date filed: February 16, 1999 Abstract: A simple screening method is provided for determining biological variations among individuals in a smoking cessation program so that a therapy regimen can be adjusted appropriately for each individual. The method includes the steps of having an individual intake a predetermined dose of nicotine, taking a saliva sample at a predetermined time subsequent to intake of the dose of nicotine, and measuring the nicotine and cotinine levels in the sample. Thereafter, a ratio is calculated which includes both the nicotine and cotinine levels as an indicator of the rate of nicotine metabolism of the individual being screened. Excerpt(s): "Not Applicable". "Not Applicable". The present invention relates generally to smoking cessation methods and, more particularly, to a method for determining biological variations among individuals in a smoking cessation program so that a therapy regimen can be adjusted appropriately for each individual. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method of producing a nicotine composition Inventor(s): Thompson, Marshall Anlauf; (Camarillo, CA) Correspondence: KELLY BAUERSFELD LOWRY & KELLEY, LLP; 6320 CANOGA AVENUE; SUITE 1650; WOODLAND HILLS; CA; 91367; US Patent Application Number: 20030108592 Date filed: August 9, 2002 Abstract: A method of producing a composition having a precise amount of nicotine appropriate for a single use by a single individual involves diluting a large quantity of nicotine into one or more successive intermediate solutions, a last of which constitutes a final solution. The final solution is then apportioned, so that each portion contains a precise quantity of nicotine appropriate for consumption in a single use by a single person. The portions may be introduced into beverages and consumed as a cigarette substitute by individuals attempting to quit smoking. This method of nicotine dilution enables accurate and inexpensive production of nicotine compositions having singleserving amounts of nicotine without requiring expensive, precision equipment for measurements. Excerpt(s): This is a continuation-in-part of U.S. patent application Ser. No. 10/015,101, filed Dec. 10, 2001. The present invention relates generally to nicotine beverages that serve as cigarette substitutes for individuals attempting to quit smoking. More particularly, the present invention relates to a method for producing a consumable composition having a precise, single-serving quantity of nicotine using conventional beverage production equipment. When the cigarette-rolling machine was patented in 1881, it enabled a relatively minor product of the time, the cigarette, to become an extremely popular product. It increased cigarette production by 5000 percent and cut the
472 Nicotine
price of an individual cigarette in half. However, the increase in the cigarette's popularity also brought with it a host of health-related problems. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method of producing a nicotine medicament and a medicament made by the method Inventor(s): Piskorz, Hanna; (Woodbridge, CA) Correspondence: BERESKIN AND PARR; SCOTIA PLAZA; 40 KING STREET WESTSUITE 4000 BOX 401; TORONTO; ON; M5H 3Y2; CA Patent Application Number: 20030103908 Date filed: December 17, 2002 Abstract: A method of producing a nicotine medicament for use in an inhaler comprises combining a nicotine formulation, a sugar and a liquid carrier including water to produce a flowable mixture and drying the flowable mixture at conditions to produce particles of the nicotine medicament suitable for delivery to the alveoli and lower airways of the person. Also disclosed is a nicotine medicament made by the method. The nicotine composition produced by this method is a composite particle suitable for tobacco replacement or withdrawal therapy. Excerpt(s): This application is a continuation of U.S. application Ser. No. 09/265,367 filed on Mar. 10, 1999 and which is still pending. This invention relates to nicotine medicaments. In particular, the invention relates to a method of producing a nicotine medicament which is suitable for inhalation. Smoking has been determined to be a contributory or causative factor in a number of diseases including respiratory diseases such as emphysema, chronic bronchitis, lung infections and lung cancer. Most regular smokers become addicted to, or dependent upon, the pharmacological effects of nicotine in tobacco smoke. Nicotine is rapidly absorbed across the blood/brain barrier and exerts a direct action on nicotine receptors in the spinal cord, autonomic ganglia and adrenal medulla. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Nicotine addiction treatment Inventor(s): Cary, Douglas D. (Great Falls, VA) Correspondence: MORGAN, LEWIS & BOCKIUS; 1800 M STREET NW; WASHINGTON; DC; 20036-5869; US Patent Application Number: 20010014678 Date filed: February 20, 2001 Abstract: The present invention encompasses methods of treating patients for tobacco addiction and nicotine addiction, for palliating the effects of nicotine withdrawal, for providing or facilitating the effects of smoking cessation therapies and as long-term smoking cessation maintenance therapy. The invention also includes related pharmaceutical compositions comprising nicotine receptor antagonists and either an anti-depressant or an anti-anxiety drug. Specific combinations of drugs (mecamylamine HCl and bupropion HCl) as well as mecamylamine in combination with certain drug classes (e.g., anti-anxiety drugs and anti-depressants) comprise the pharmaceutical
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compositions disclosed. These compositions are also contemplated for use in the treatment of cocaine addiction and the treatment of alcohol dependence. Excerpt(s): The present invention relates to pharmaceutical compositions and methods of using these compositions to treat patients for tobacco addiction and nicotine addiction, to palliate the effects of nicotine withdrawal and to enhance the outcomes of other smoking cessation therapies. Each agent of the pharmaceutical compositions disclosed has an unique mechanism of action, and when administered concurrently, the combined drugs provide unexpected advantages over existing therapies. Tobacco addiction represents the most important preventable cause of illness and death in our society, responsible for more than 400,000 deaths each year. Currently, one out of five Americans smoke cigarettes, representing almost 50 million smokers in the United States alone. Half of all smokers will die of diseases directly related to tobacco use, and many smokers will suffer significant morbidity. Approximately 15 million smokers try to quit, but only one million of those succeed in smoking cessation each year. A great deal of evidence supports the view that people continue to smoke because of the reinforcing effects of nicotine. Relevant findings include the fact that when allowed to control the nicotine content of each puff, smokers previously deprived of cigarettes, or administered a centrally acting nicotine antagonist, select higher nicotine concentrations. Moreover, under certain conditions, smokers, as well as animals, will self-administer intravenous nicotine. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Nicotine and chocolate compositions Inventor(s): Lindberg, Nils-Olof; (Malmo, SE), Landh, Thomas; (Lund, SE) Correspondence: FULBRIGHT & JAWORSKI, LLP; 1301 MCKINNEY; SUITE 5100; HOUSTON; TX; 77010-3095; US Patent Application Number: 20030119879 Date filed: October 15, 2002 Abstract: The present invention is drawn to nicotine-containing pharmaceutical compositions that comprise chocolate and method of using the compositions in different therapies, such as nicotine replacement therapy. Excerpt(s): This application claims priority to U.S. Provisional Application No. 60/329,571, which was filed on Oct. 15, 2001. This invention relates to novel pharmaceutical compositions of nicotine and use thereof. More particularly, the present invention relates to compositions comprising nicotine and chocolate, methods to prepare the compositions, and to methods for using the compositions in nicotine replacement therapy (NRT), including tobacco substitution and smoking cessation. Nicotine replacement therapy as a smoking cessation strategy has been successful in the past. Previous nicotine-containing compositions aiming towards the purpose of reducing nicotine craving for subjects wishing to stop their use of tobacco products include i.e., U.S. Pat. No. 3,845,217 disclosing chewable compositions, U.S. Pat. No. 4,579,858 disclosing high-viscous nicotine nose-drop compositions, U.S. Pat. No. 5,525,351 disclosing nicotine-containing saliva-soluble gels, U.S. Pat. No. 5,656,255 disclosing low-viscous nicotine-containing compositions suitable for nasal spray administration, U.S. Pat. No. 4,920,989 and U.S. Pat. No. 4,953,572 disclosing the use of inhalation aerosol, BP 1,528,391 and BP 2,030,862 disclosing liquid aerosol formulations adapted as mouth-sprays, and devices for transdermal delivery of nicotine.
474 Nicotine
Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Nicotine and cocoa powder compositions Inventor(s): Lindberg, Nils-Olof; (Malmo, SE) Correspondence: FULBRIGHT & JAWORSKI, LLP; 1301 MCKINNEY; SUITE 5100; HOUSTON; TX; 77010-3095; US Patent Application Number: 20030087937 Date filed: October 15, 2002 Abstract: The present invention relates to a nicotine-containing pharmaceutical composition and methods of using the composition in therapies, such as nicotine replacement therapy. Excerpt(s): This application claims priority to U.S. Provisional Application No. 60/329,369, which was filed on Oct. 15, 2001. This invention relates to novel pharmaceutical compositions of nicotine and use thereof. More particularly, the present invention relates to compositions comprising nicotine and cocoa powder, methods to prepare the compositions, and to methods for using the compositions in nicotine replacement therapy (NRT), including tobacco substitution and smoking cessation. Nicotine replacement therapy as a smoking cessation strategy has been successful in the past. Previous nicotine-containing compositions aiming towards the purpose of reducing nicotine craving for subjects wishing to stop their use of tobacco products include e.g., U.S. Pat. No. 3,845,217 disclosing chewable compositions, U.S. Pat. No. 4,579,858 disclosing high-viscous nicotine nose-drop compositions, U.S. Pat. No. 5,525,351 disclosing nicotine-containing, saliva-soluble gels, U.S. Pat. No. 5,656,255 disclosing low-viscous nicotine-containing compositions suitable for nasal spray administration, U.S. Pat. No. 4,920,989, U.S. Pat. No. 4,953,572 and U.S. Pat. No. 5,167,242 disclosing the use of inhalation aerosol, BP 1,528,391 and BP 2,030,862 disclosing liquid aerosol formulations adapted as mouth-sprays, and devices for transdermal delivery of nicotine. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Nicotine compositions Inventor(s): Landh, Tomas; (Lund, SE), Andersson, Sven; (Odakra, SE), Jonn, Stefan; (Helsingborg, SE) Correspondence: FULBRIGHT & JAWORSKI, LLP; 1301 MCKINNEY; SUITE 5100; HOUSTON; TX; 77010-3095; US Patent Application Number: 20030176467 Date filed: March 14, 2003 Abstract: The present invention relates to compositions of nicotine comprising polar lipids and one or more fatty acids. The compositions may further comprise one or more pharmaceutically acceptable excipients selected from the group consisting of flavoring agents, sweeteners, buffering agents, chewing gum base and preservatives. In specific aspects, the invention is directed to compositions comprising nicotine and one or more polar lipids which are capable of forming a liquid crystalline phase or a precursor or
Patents 475
offspring thereof when placed in a polar solvent. The composition can be administered via a buccal, pulmonary, nasal or topical route. Excerpt(s): This invention relates to compositions comprising nicotine and methods to prepare said compositions useful in drug therapy, preferably tobacco substitution or replacement of tobacco and smoking cessation. Nicotine replacement therapy as a smoking cessation strategy has been successful in the past. Previous nicotine-containing compositions aimed towards the purpose of reducing nicotine craving for subjects wishing to stop their use of tobacco products include e.g., U.S. Pat. No. 3,845,217 disclosing chewable compositions, U.S. Pat. No. 4,579,858 disclosing high-viscous nicotine nose-drop compositions, AU 664 415 disclosing low-viscous nicotine-containing compositions suitable for nasal spray administration, U.S. Pat. No. 4,920,989 and 4,953,572 disclosing the use of inhalation aerosol, BP 1,528,391 and BP 2,030,862 disclosing liquid aerosol formulations adapted as mouth sprays, and for transdermal delivery of nicotine and U.S. Pat. No. 4,915,950 disclosing the manufacturing of devices for transdermal delivery of nicotine. Several products based on the above mentioned patents are now marketed on an international scale. EP 126,751 B1 discloses controlled release compositions for the delivery of biologically active materials. According to the invention described therein, a biologically active material is provided in formulations of amphiphilic substances capable of forming liquid crystalline phases when placed in contact with a liquid to be constituting any part of the polar compartment of the then formed thermodynamically stable phase. The liquid crystalline phases utilised in the aforesaid invention are preferably, but not exclusively, the group of cubic and hexagonal, liquid crystalline phases. WO 95/26715 discloses bioadhesive compositions using fatty acid esters forming liquid crystals, preferably the group of cubic and hexagonal, liquid crystalline phases. U.S. Pat. No. 5,371,109 discloses the use of an L2phase composed of mixtures of mono- and triglycerides and polar solvent as a controlled composition for biological active materials. The use of fatty acids in such mixtures is, however, not disclosed. U.S. Pat. No. 5,531,925 discloses methods of preparing particles, or precursors thereof, of the aforementioned liquid crystalline phases or precursors thereof of reversed/inversed type II structure. WO 97/13528 also discloses liquid crystalline phases. Although in the latter nicotine is mentioned in the description, within a long list of drugs, no compositions according to the examples may be formulated with nicotine. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Nicotine delivery compositions Inventor(s): Blank, Izhak; (Kiriat Ono, IL) Correspondence: Neal L. Rosenberg, Esq. AMSTER, ROTHSTEIN & EBENSTEIN; 90 Park Avenue; New York; NY; 10016; US Patent Application Number: 20020131993 Date filed: January 12, 2001 Abstract: A composition containing nicotine and an uncrosslinked, water-insoluble vinylpyrrolidone copolymer is applied on the skin of patients in the form of a gel, ointment, solution, suspension or film which slowly releases nicotine and creates levels of the drug in the blood to reduce nicotine-craving in smokers, thereby assisting in smoking-cessation programs.
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Excerpt(s): This invention relates to a new method for transdermal nicotine delivery which is particularly useful as a smoking-cessation aid in the treatment of addiction to cigarette smoking. Nicotine is the most widely used addictive drug. Nicotine is more addictive than heroin, cocaine and alcohol. Every year, 30% of the smokers try to get rid of the habit but only about 3% succeed. In the United States alone there are 50 million smokers, each consuming an average of 10,000 cigarettes a year. This is estimated to cause 420,000 deaths due to lung and heart diseases and cancer. There are at present 1.1 billion smokers in the whole world and the World Health Organization has indicated that by the year 2020 tobacco related illness will be the cause of around 10% of all diseases affecting mankind and will be responsible for 14% of all deaths. The use of tobacco products produces a yearly loss of 200 billion dollars to the economy. In Israel the problem is quite severe. Recent data shows that 28% of adults and 18% of youngsters (below 13 years old) are smokers. It is estimated that every year 10,000 people die due to the smoking habit and another 1,400 die due to passive smoking. Life insurance companies charge approximately double premium payments to smokers as compared to non-smokers. For a one million shekel life insurance policy ($=4 shekel) a 50 year old man will pay 6,690 shekel if he is a smoker and only 3,540 shekel if he is not. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Nicotine free cigarette substitute Inventor(s): Park, Jin Hyun; (Los Angeles, CA), Oh, Soo Han; (Northridge, CA), Kim, Hong Bin; (Los Angeles, CA) Correspondence: Eugene Oak, Ph. D., J. D., Patent Attorney; 610 S. Van Ness Ave. Los Angeles; CA; 90005; US Patent Application Number: 20030131857 Date filed: January 16, 2002 Abstract: A composition of material for manufacturing nicotine free cigarette substitutes.The composition of material of this invention, maintaining the taste and flavor of cigarette, without tobacco leaf, is composed of including but not limited to leaf powder of Samilax China L and leaf powder of Gomphrena Globosa L.The cigarette substitute of this invention is manufactured and packed like normal cigarettes, 20 cigarettes per pack. The substitute emits no nicotine and no class A carcinogenic substances when inhaled by a human. The cigarette substitute has good cancerresistance. It cures the harmful effecrs to a human body due to poison such as heavy metals of mercury, nickel, and cadmium imposed by use of regular cigarettes.The substitute of this invention helps to quit smoking and eliminates the poisons from the blood of the pre-smokers. Excerpt(s): The present invention relates to a composition of materials for manufacturing a cigarette substitute which tastes like normal cigarette but contain no class A carcinogenic substances, nicotine and tar. The present invention relates to a composition of materials for manufacturing a cigarette substitute tastes like normal cigarette but contain no class A carcinogenic substances, nicotine and tar, meanwhile having cancer-resisting effect and curing effect of heavy metal poison. U.S. Pat. No. 6, 200, 391 to Oshiro teaches to add a compounds containing ascorbic acid, a salt or isomer thereof, a chlorophyll-containing material, and potassium nitrate to obtain a tobacco flavoring agent lowering the tar or nicotine content of tobacco smoke, maintaining a burning portion of tobacco in a stable state, and preserving its powdery state. The
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tobacco-flavoring agent was deposited on the tips of the cigarettes mixed with shredded tobacco leaves. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Nicotine in therapeutic angiogenesis and vasculogenesis Inventor(s): Heescheen, Christopher; (Menlo Park, CA), Cooke, John; (Palo Alto, CA), Jang, James; (San Bruno, CA), Tsao, Phillip; (San Jose, CA) Correspondence: BOZICEVIC, FIELD & FRANCIS LLP; 200 MIDDLEFIELD RD; SUITE 200; MENLO PARK; CA; 94025; US Patent Application Number: 20020128294 Date filed: May 15, 2002 Abstract: The present invention features methods for induction of angiogenesis by administration of nicotine or other nicotine receptor agonist. Induction of angiogenesis by the methods of the invention can be used in therapeutic angiogenesis in, for example, treatment of ischemic syndromes such as coronary or peripheral arterial disease. Excerpt(s): This application claims the benefit of U.S. Provisional Application Serial No. 60/146,233, filed Jul. 28, 1999, which application is incorporated herein by reference. The invention relates generally to the field of regulation of angiogenesis and vasculogenesis, particularly to induction of angiogenesis to promote growth of new vasculature. Angiogenesis and vasculogenesis are processes involved in the growth of blood vessels. Angiogenesis is the process by which new blood vessels are formed from extant capillaries, while vasculogenesis involves the growth of vessels deriving from endothelial progenitor cells. Angiogenesis and vasculogenesis, and the factors that regulate these processes, are important in embryonic development, inflammation, and wound healing, and also contribute to pathologic conditions such as tumor growth, diabetic retinopathy, rheumatoid arthritis, and chronic inflammatory diseases (see, e.g., U.S. Pat. No. 5,318,957; Yancopoulos et al. (1998) Cell 93:6614; Folkman et al. (1996) Cell 87;1153-5; and Hanahan et al. (1996) Cell 86:353-64). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Nicotine mucosal spray Inventor(s): Jones, Richard L. (Edmonton, CA) Correspondence: Anita Nador; Bereskin & Parr; 40 King Street West; Box 401; Toronto; ON; M5H 3Y2; CA Patent Application Number: 20020054856 Date filed: October 24, 2001 Abstract: A composition for administration to the nasal mucosa of a subject comprises a solution of nicotine or a pharmaceutically acceptable salt thereof in a pharmaceutically acceptable solvent. The composition has a nicotine concentration less than 10 mg/ml. The composition used alone assists in reduction of the desire of a subject to smoke tobacco. It also reduces the nasal symptoms associated with administration of higher concentrations of nicotine to the nasal mucosa.
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Excerpt(s): This application claims priority from U.S. Provisional Patent Application No. 60/243,205, filed Oct. 24, 2000, the entirety of which is herein incorporated by reference. The invention relates to the field of nicotine mucosal sprays, to compositions comprising nicotine that can be administered in a mucosal spray form and to methods and uses therefore. In one embodiment, the invention relates to compositions and methods useful for subjects who wish to reduce tobacco smoking. Due to the reported harmful effects of tobacco smoke and also due to the current social attitudes to smoking, resulting in everincreasing smoke-free public areas, there is great pressure on tobacco smokers to stop smoking or to find a more socially acceptable alternative. To achieve these goals various forms of nicotine-replacement therapy have been suggested. One such therapy is a nicotine nasal spray (NNS). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Nicotine receptor ligands Inventor(s): Efange, S. Mbua Ngale; (Plymouth, MN) Correspondence: SCHWEGMAN, LUNDBERG, WOESSNER & KLUTH, P.A. P.O. BOX 2938; MINNEAPOLIS; MN; 55402; US Patent Application Number: 20030027810 Date filed: November 30, 2001 Abstract: The invention provides nicotine receptor agonists of formula I: 1wherein R.sub.1, x, y, and n have any of the values given in the specification, or a pharmaceutically acceptable salt thereof, as well as pharmaceutical compositions comprising such a compound or salt, methods for preparing such a compound or salt, and methods for modulating (e.g. antagonizing or activating) nicotine receptors with such a compound or salt. Excerpt(s): Acetylcholine, a major neurotransmitter in mammalian organisms, is released from central, sympathetic and peripheral neurons. Acetylcholine is involved in a wide range of biological functions including motor, sensory, learning and memory, sexual activity, sleep, and autonomic control of cardiovascular, respiratory, gastrointestinal and urogenital functions. Modulation of cholinergic function has been found to have beneficial effects in a number of pathologies such as Alzheimer's disease, Parkinson's disease and olivopontocerebellar atrophy. Actions of the neurotransmitter acetylcholine are modulated by two classes of receptors, muscarinic and nicotinic, on the basis of the effects of the prototypical cholinergic agonists, muscarine and nicotine. Nicotine administration increases dopamine efflux in the striatum, nucleus accumbens and cortex. Nicotine administration also causes norepinephrine release in cortex and hippocampus and glutamate release in the cortex. The effects of nicotine on glutamate have also been demonstrated in behavioral tests where NMDA antagonist MK-801 eliminated the memory improvement caused by nicotine. Nicotine also stimulates acetylcholine release and thus exerts some of its actions via muscarinic receptors. Nicotine affects cardiovascular function by sympathetic neural stimulation. The endocrine-mediating effects of nicotine release include a release of beta-endorphins, and stimulation of ACTH and cortisol release. Nicotine also induces lipolysis and subsequent release of free fatty acids into the circulation. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Nicotine salts having improved taste, process for their preparation and their use Inventor(s): Dorr, Margit; (Hohen-Suelzen, DE), Burgard, Andreas; (Frankfurt am Main, DE) Correspondence: ProPat LLC; Suite 400; 6230 Fairview Rd; Charlotte; NC; 28210; US Patent Application Number: 20010029959 Date filed: March 16, 2001 Abstract: Salts formed from nicotine and anion-forming sweeteners, for example acesulfame or acesulfame-K, in a molar ratio of 1:1 or 1:2, in which case the sweetener molecules can be identical or different, are distinguished by a pleasant sweet taste which masks the nicotine taste even after a long residence time in the mouth, and are therefore suitable for producing preparations, in particular chewing gum, chewing tablets or compressed compositions, which can be used for oral administration of nicotine, for example in withdrawal from smoking. Excerpt(s): Owing to continuous consumption of cigarettes, smokers are habituated to regularly taking nicotine. Because of the disadvantageous effects of smoking on health, many smokers are interested in giving up smoking. This intention however fails in many cases owing to the fact that the regular consumption of nicotine has already led to a physical dependency. For slow withdrawal, various routes have been proposed, for example applying nicotine to the skin in the form of impregnated plasters or supplying it orally, for example via a chewing gum (U.S. Pat. No. 5,488,962). Supply via chewing gum additionally has the advantage that the oral intake compensates for the need for sucking cigarettes. However, nicotine has a taste which, when consumed alone, is perceived as unpleasant. It is generally described as sharp to pepper-like and bitter. This unpleasant taste hinders the acceptance of chewing gum with added nicotine which should be chewed regularly for withdrawal from smoking, particularly in the initial phase. In order to improve the acceptance of nicotine-containing chewing gums or other preparations which can be consumed orally, there is therefore the requirement for improving or masking the unpleasant taste of nicotine. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Nicotine therapy method and oral carrier for assuaging tobacco-addiction Inventor(s): Smith, Steve; (Richmond, CA), Wilhelmsen, Paul C. (Alamo, CA) Correspondence: RICHARD BREWSTER MAIN; 23777 MINES ROAD; LIVERMORE; CA; 94550; US Patent Application Number: 20020002189 Date filed: August 23, 2001 Abstract: A method for assuaging tobacco addiction comprises pulsing doses of nicotine into a user's bloodstream so it reaches the brain before passing through the liver. A nicotine-burst tablet is held in the mouth by a user to receive each nicotine-pulse dose. The tablet is configured to suddenly release its entire nicotine payload from an otherwise inert or benign material. Such nicotine payload is relatively small, e.g., under one milligram. The therapeutic effects depend on the change of nicotine levels in the blood over a change in time. Rapid nicotine onset of a small dose is more assuaging than a slow build-up to a high dosage. An oral carrier comprises a nicotine saturated instant-
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dissolve paper that delivers one nicotine pulse. An additive prevents abuse by causing excessive use to catalyze a foul taste or sickening sensation. Excerpt(s): This Application is a continuation-in-part of U.S. patent application Ser. No. 09/771,454, filed Jan. 29, 2001, and which is, in turn, a continuation-in-part of U.S. patent application Ser. No. 09/292,045, filed Apr. 14, 2001, and now issued as U.S. Pat. No. 6,248,760, on Jun. 19, 2001. Such are incorporated herein by reference. The present invention relates to tobacco-addiction therapies, and more particularly to methods and devices for assuaging nicotine cravings in users. Tobacco-addiction is a serious health problem through out the world. The hundreds of compounds carried along with the nicotine cause most of the trouble, but the nicotine is responsible for the chemical addiction. Tobacco users find it too difficult to quit because both the nicotine cravings and ritual behaviors are too severe and ingrained. The prior art has therefore developed a multitude of therapies, devices, and methods for helping people quit tobacco. Many of them follow similar ritual patterns of putting things in the mouth. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Pharmaceutical composition for the prevention and treatment of nicotine addiction in a mammal Inventor(s): Watsky, Eric Jacob; (Stonington, CT), O'Neill, Brian T. (Old Saybrook, CT), Coe, Jotham W. (Niantic, CT), Harrigan, Edmund P. (Old Lyme, CT), Sands, Steven B. (Stonington, CT) Correspondence: PFIZER INC; 150 EAST 42ND STREET; 5TH FLOOR - STOP 49; NEW YORK; NY; 10017-5612; US Patent Application Number: 20030109544 Date filed: January 21, 2003 Abstract: Pharmaceutical compositions are disclosed for the treatment of nicotine dependence or addiction, tobacco dependence or addiction, reduction of nicotine withdrawal symptoms or aiding in the cessation or lessening of tobacco use or substance abuse. The pharmaceutical compositions are comprised of a therapeutically effective combination of a nicotine receptor partial agonist and an anti-depressant or anxiolytic agent and a pharmaceutically acceptable carrier. The method of using these compounds is also disclosed. Excerpt(s): The present invention relates to pharmaceutical compositions for the treatment of nicotine dependence or addiction in a mammal (e.g. human) comprising a nicotine receptor partial agonist (NRPA) and an anti-depressant or anxiolytic agent. The term NRPA refers to all chemical compounds which bind at neuronal nicotinic acetylcholine specific receptor sites in mammalian tissue and elicit a partial agonist response. A partial agonist response is defined here to mean a partial, or incomplete functional effect in a given functional assay. Additionally, a partial agonist will also exhibit some degree of antagonist activity by its ability to block the action of a full agonist (Feldman, R. S., Meyer, J. S. & Quenzer, L. F. Principles of Neuropsychopharmacology, 1997; Sinauer Assoc. Inc.). The present invention may be used to treat mammals (e.g. humans) for tobacco dependence or addiction and nicotine dependence or addiction; to palliate the effects of nicotine withdrawal and to enhance the outcomes of other smoking cessation therapies. The invention also relates to aryl fused azapolycylic compounds that bind to neuronal nicotinic acetylcholine specific receptor sites and are useful in modulating cholinergic function and are referred to in
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WO 9818798-A1, WO 9935131-A1 and WO 9955680-A1. The foregoing applications are owned in common with the present application and are incorporated herein by reference in their entireties. The NRPA compounds that bind to neuronal nicotinic receptor sites can be used in combination with an anti-depressant such as for example, a tricyclic anti-depressant (e.g. amitryptyline, imipramine), a serotonin reuptake inhibitor anti-depressant (SRI) (e.g. sertraline, paroxetine, or fluoxetine), an atypical antidepressant (bupropion, nefazodone), or a monoamine oxidase inhibitor (e.g., phenelzine, tranylcypromine) in order to treat the depression associated with addiction such as to nicotine or tobacco, alcohol dependence, cocaine addiction or tobacco or nicotine dependence independently of other psychiatric illness. The compounds that bind to neuronal nicotinic receptor sites can be used in combination with anxiolytic agents, such as for example, a benzodiazepine (e.g. diazepam, alprazolam, chlordiazepoxide) or non-benzodiazepine anxiolytics (e.g. buspirone, hydroxyzine, doxepin) in order to treat the anxiety associated with addiction such as to nicotine or tobacco, alcohol dependence, cocaine addiction or tobacco or nicotine dependence independently of other psychiatric illness. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Preparation of tobacco having reduced contents of nicotine and tar Inventor(s): Sun, Lee Kyu; (Seoul, KR) Correspondence: THE LAW OFFICES OF EUGENE M. LEE, PLLC; 1101 WILSON BOULEVARD; SUITE 2000; ARLINGTON; VA; 22209; US Patent Application Number: 20020153018 Date filed: February 13, 2002 Abstract: A method for the preparation of tobacco, specifically a method for the preparation of tobacco having reduced contents of nicotine and tar by adding playcodi radix (broad bellflower), ginseng radix (Panax ginseng) and peach kernel (persicae semen) or Eum-Yang-Kwak (dried leaves of epimedii herbal tea (Epimedium koreanum)) into tobacco leaves which have been cut into a specified size to reduce the toxicity of tobacco, to remove the nicotine and tar contained in the tobacco and to improve the fragrance of tobacco, by which an improvement of health can be achieved by smoking the tobacco. Excerpt(s): The present invention relates to a method for the preparation of tobacco, specifically to a method for the preparation of tobacco having reduced contents of nicotine and tar by adding playcodi radix (broad bellflower), ginseng radix (Panax ginseng) and peach kernel (persicae semen) or Eum-Yang-Kwak (dried leaves of epimedii herbal tea (Epimedium koreanum)) into tobacco leaves which have been cut into a specified size to reduce the toxicity of tobacco, to remove the nicotine and tar contained in the tobacco and to improve the fragrance of tobacco, by which an improvement of health can be achieved by smoking the tobacco. Playcodi radix (broad bellflower) of 2.about.3 years old, ginseng radix (Panax ginseng) of 1 year old and peach kernel (persicae semen) or Eum-Yang-Kwak (dried leaves of epimedii herbal tea (Epimedium koreanum)) are dried under shade and are pulverized into a size of 100-130 meshes and are mixed together in an equal proportion. The mixture of playcodi radix (broad bellflower), ginseng radix (Panax ginseng) and peach kernel (persicae semen) or Eum-Yang-Kwak (dried leaves of epimedii herbal tea (Epimedium koreanum)) is mixed to tobacco leaves which have been cut into a specific size at the proportion of 0.9% herb
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mixture and 99.1% tobacco leaves to manufacture cigarette and/or tobacco, thereby improving fragrance of and reducing the content of nicotine and tar in tobacco. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Transdermal or transmucosal dosage forms with a nicotine-containing active substance combination for smoker disintoxication Inventor(s): Frick, Ulrich; (Pfalzfeld, DE), Theobald, Frank; (Bad Breisig, DE) Correspondence: BIRCH STEWART KOLASCH & BIRCH; PO BOX 747; FALLS CHURCH; VA; 22040-0747; US Patent Application Number: 20030049308 Date filed: October 15, 2002 Abstract: A transdermal or transmucosal pharmaceutical administration form for treating nicotine dependency or for disaccustoming smokers, comprising nicotine, a nicotine salt, a nicotine derivative or a nicotinergic substance in combination with at least one further active substance is characterized in that as additional active substance(s) it comprises at least one substance which acts on the central nervous system. Excerpt(s): Transdermal or transmucosal administration forms with a nicotinecontaining active substance combination for disaccustoming smokers. The invention relates to transdermal or transmucosal pharmaceutical administration forms for treating nicotine dependency or for disaccustoming smokers, comprising nicotine, a nicotine salt, a nicotine derivative or a nicotinergic substance, in combination with a further active substance. The invention further relates to the use of such administration forms for treating nicotine dependency, for the purpose of nicotine substitution, or for disaccustoming smokers, and also to the use of nicotine and/or its salts or derivatives for preparing transdermal or transmucosal pharmaceutical forms for treating nicotine dependency. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Use of GABAA inverse agonists in combination with nicotine receptor partial agonists, estrogen, selective estrogen modulators, or vitamin E for the treatment of cognitive disorders Inventor(s): Villalobos, Anabella; (Niantic, CT) Correspondence: PFIZER INC; 150 EAST 42ND STREET; 5TH FLOOR - STOP 49; NEW YORK; NY; 10017-5612; US Patent Application Number: 20020193360 Date filed: February 26, 2002 Abstract: A pharmaceutical composition and method of treatment of diseases of cognitive dysfunction in a mammal comprising administration of a GABA.sub.A inverse agonist or a pharmaceutically acceptable salt thereof; and a nicotine receptor partial agonist, an estrogenic agent, selective estrogen receptor modulator or vitamin E or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier. The GABA.sub.A inverse agonist, and nicotine receptor partial agonist, estrogen, selective estrogen receptor modulator or vitamin E are present in amounts that render the
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composition effective enhancing cognition or in the treatment of diseases of cognitive dysfunction including but not limited to Alzheimer's Disease (AD), mild cognitive impairment, age-related cognitive decline, vascular dementia, Parkinson's disease, Huntington's disease, memory impairment associated with depresssion or anxiety, schizophrenia, Down's syndrome, stroke, traumatic brain injury (TBI), AIDS associated dementia and attention deficit disorder. The method of using these compositions is also disclosed. Excerpt(s): This application claims priority from U.S. provisional application Serial No. 60/272,566, filed Mar. 1, 2001, which is incorporated herein by reference in its entirety. The present invention relates to pharmaceutical compositions for the prevention and/or treatment of diseases of cognitive dysfunction in a mammal comprising GABA.sub.A inverse agonists in combination with nicotine receptor partial agonists (NRPA), estrogen, selective estrogen receptor modulators (SERMS) or vitamin E and a pharmaceutically acceptable carrier. The pharmaceutical compositions are useful in enhancing memory in patients suffering from diseases of cognitive dysfunction such as, but not limited to, Alzheimer's Disease (AD), mild cognitive impairment, age-related cognitive decline, vascular dementia, Parkinson's disease, Huntington's disease, memory impairment associated with depression or anxiety, schizophrenia, Down's syndrome, stroke, traumatic brain injury (TBI), AIDS associated dementia and attention deficit disorder. Cognitive and/or degenerative brain disorders are characterized clinically by progressive loss of memory, cognition, reasoning, judgment and emotional stability that gradually leads to profound mental deterioration and ultimately death. In an example of such disorders, AD is a common cause of progressive mental failure (dementia) in aged humans and is believed to represent the fourth most common medical cause of death in the United States. In particular, AD is associated with degeneration of cholinergic neurons in the basal forebrain that play a fundamental role in cognitive functions, including memory [Becker et al., Drug Development Research, 12, 163-195 (1988)]. Cognitive and/or degenerative brain disorders have been observed in varied races and ethnic groups worldwide and presents a major public health problem. These diseases are currently estimated to affect about two to three million individuals in the United States alone. These diseases are incurable with presently used medications and will increase worldwide as the human lifespan increases. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
Keeping Current In order to stay informed about patents and patent applications dealing with nicotine, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “nicotine” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on nicotine. You can also use this procedure to view pending patent applications concerning nicotine. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.
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CHAPTER 7. BOOKS ON NICOTINE Overview This chapter provides bibliographic book references relating to nicotine. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on nicotine include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.
Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “nicotine” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on nicotine: •
Cigarettes, Nicotine, and Health: A Biobehavioral Approach Source: Thousand Oaks, CA, SAGE Publications, 192 p., 2001. Contact: SAGE Publications, Inc., 2455 Teller Road, Thousand Oaks, CA 91320. INTERNET/EMAIL: www.sagepub.com;
[email protected]. Summary: Cigarettes, Nicotine, and Health: A Biobehavioral Approach addresses worldwide tobacco use and its health consequences from a multidisciplinary perspective. Cigarette smoking, the most common form of tobacco use in many regions of the world, has enormous relevance for health promotion and disease prevention as it is the largest preventable cause of disability and death in many industrialized nations and a disturbingly accelerating trend in developing countries. A cigarette is an extremely sophisticated drug delivery system, the drug being nicotine. Nicotine is a psychoactive, addictive drug that is 10 times more potent, milligram for milligram, than cocaine and morphine. Chapters in the text include (1) the history of the use of nicotine;
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(2) who smokes and what kills them; (3) what nicotine does to the body; (4) the natural history of a dependence disorder; (5) tobacco use as nicotine addiction; (6) smoking, drinking, and drug taking: a behavioral syndrome; (7) low-tar, light cigarettes: lessons from a dangerous boondoggle; (8) helping smokers quit; and (9) tobacco, public health, and policy. •
Nicotine Source: Springfield, NJ, Enslow Publishers, Inc., 128 p., 1995. Contact: Enslow Publishers, Inc., Box 699, 44 Fadem Road, Springfield, NJ 07081-0699. (201) 379-8890. FAX: (201) 379-7940. Summary: Nicotine examines the impact of nicotine addiction on the physical and emotional well being of both the individual and society. The author begins with a summary of the history of tobacco use and ends with a synopsis of current legislation and community actions. The health effects of nicotine can include cancers, lung diseases, and heart diseases, as well as complication s of acquired immunodeficiency syndrome and pregnancy. Despite the health risks, many Americans, including children and teens, continue to smoke cigarettes or use such products as snuff and chew. The author discusses the use of nicotine among women and minority groups, and the use of advertising to promote cigarette smoking. Although tobacco use was once not only accepted but encouraged throughout society, the fashion associated with tobacco use diminished once the health effects of smoking were discovered. Both genetics and environment may play a role in the smoking habits of families. While teens may believe that they will not become addicted, nicotine is addictive; its use usually results in an unmanageable problem. Although quitting nicotine use may be difficult, the reasons for quitting, such as improved health, more energy, improved family relations, and more money, are enticing. Ways to quit include self instruction through booklets, videotapes, and quit kits; the use of nicotine chewing gum and patches; cigarette brand switching; quit smoking programs; and other less proven methods such as hypnosis, acupuncture, and aversion therapy. The author discusses the school programs and federal, state and local government organizations designed to prevent and/or control cigarette smoking. The special health hazards of secondhand smoke include cancer, heart disease, and asthma. The author provides questions for discussion at the end of each chapter, as well as the names and contact numbers of organizations which help individuals to quit tobacco use.
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Growing Up Tobacco Free: Preventing Nicotine Addiction in Children and Youths Source: Washington, DC, National Academy Press, 306 p., 1994. Contact: National Academy Press, Marketing Department, 2101 Constitution Avenue, NW., Washington, DC 20418. (202) 334-3180. Summary: Growing Up Tobacco Free: Preventing Nicotine Addiction in Children and Youths explains nicotine's effects and the process of addiction, and documents the search for an effective approach to preventing the use of cigarettes, chewing and spitting tobacco, and snuff by children and youths. The book has nine chapters. Chapter one, Toward a Youth-centered Prevention Policy, addresses the need for a youth-centered tobacco control policy and suggests elements of such a policy. Chapter two, Nature of Nicotine Addiction, discusses the general aspects of nicotine addiction, nicotine dependency in youths, and the nature of tobacco products. Chapter three, Social Norms and the Acceptability of Tobacco Use, addresses (1) the function of social norms, (2) the emerging tobacco-free norm, (3) tobacco use as perceived by children and youths, (4)
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opportunities for promoting a tobacco-free norm, and (5) advocacy for a tobacco-free norm. Chapter four, Tobacco Advertising and Promotion, discusses (1) shifting trends in tobacco marketing; (2) tobacco market segmentation; (3) the appeal of tobacco advertising to children and youths; and (4) a critical assessment of studies on advertising recall, advertising expenditures, and tobacco companies. Chapter five, Prevention and Cessation of Tobacco Use: Research-Based Programs, discusses (1) prevention of smoking, (2) prevention of smokeless tobacco use, (3) adolescent cessation of smoking, and (4) cessation of smokeless tobacco use. Chapter six, Tobacco Taxation in the United States, discusses tax rates in the United States and other industrialized countries, the effect of excise taxes on consumption, and arguments for against higher tobacco taxes. Chapter seven, Youth Access to Tobacco Products, addresses the background of youth access measures, recent initiatives, the benefits of reducing access, designing a youth access policy, and suggestions for additional policy initiatives and research. Chapter eight, Regulation of the Labeling, Packaging, and Contents of Tobacco Products, discusses tobacco as a unregulated hazard, warnings and packaging, and the regulation of constituents of tobacco products. Chapter nine, Coordination of Policies and Research, addresses the roles of the federal government, state and local governments, private sector organizations; linkage between excise tax revenues and tobacco control program funding; and options and recommendations for coordination. •
Nicotine in Psychiatry: Psychopathology and Emerging Therapeutics Source: Washington, DC, American Psychiatric Press, Inc., 296 p., 2000. Contact: American Psychiatric Press, Inc., 1400 K Street, NW., Washington, DC 20005. INTERNET/EMAIL: www.appi.org. Summary: Nicotine in Psychiatry: Psychopathology and Emerging Therapeutics examines the importance of nicotine and nicotinic pharmacology in psychiatry and neuroscience. The first section addresses the (1) neurobiology and clinical pathophysiology of neuronal nicotine acetylcholine receptors, (2) pharmacokinetics and pharmacodynamics of nicotine, (3) behavioral factors influencing the effects of nicotine, and (4) addictive capacity of nicotine. The second section deals with clinical applications including (1) nicotine and major mental disorders; (2) smoking, nicotine, and mood; (3) nicotinic cholinergic systems in Alzheimer's and Parkinson's diseases; (4) smoking, nicotine, and movement disorders; (5) nicotine effects and attention deficit/hyperactivity disorder; (6) nicotine replacement therapies and beyond; (7) behavioral treatment of cigarette smoking and nicotine dependence; and (8) nicotine and nicotinic systems in psychiatry, past and future. As regards exposure to nicotine during pregnancy, there is evidence that indicates that pregnancy produces large changes in the metabolism of nicotine and cotinine. Increased clearance of cotinine levels explains the observation that cotinine levels, normalized for cigarettes smoked per day, are much lower in pregnant than in nonpregnant women. The implications of rapid metabolism for smoking behavior and smoking cessation treatment during pregnancy remain to be determined. Nicotine may arrest neuronal replication and differentiation in the developing fetus and may be associated with sudden infant death syndrome. While nicotine administration in adults seems to improve attentiveness, prenatal nicotine exposure has been associated with attention impairment. Children of women who smoke during pregnancy are more likely to develop cognitive and learning deficits, including (1) attention deficit/hyperactive disorder, (2) impaired attention and orientation, and (3) poor impulse control. Long-lasting deficits in cognitive function after maternal smoking during pregnancy have been seen in most studies. Recent
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evidence suggests that smoking during pregnancy increases the risk for attention deficit/hyperactivity disorders and reduced childhood IQ scores. •
Nicotine Safety and Toxicity Source: New York, NY, Oxford University Press, 214 p., 1998. Contact: Oxford University Press, 198 Madison Avenue, New York, NY 10016. Summary: Nicotine Safety and Toxicity reviews the current scientific understanding of the safety and toxicity of nicotine. Papers from a symposium entitled The Safety and Toxicity of Nicotine, held on December 6, 1996, in Braselton, Georgia, form the basis for the chapters in this book. Specific chapter topics in Part I concern nicotine and cardiovascular diseases, with special attention given to (1) pharmacokinetic and pharmacodynamic considerations, (2) cardiovascular toxicity of nicotine in animals, (3) cardiovascular effects of cigarette smoke and snuff, and (4) the toxicity of nicotine replacement in patients with coronary artery disease. Part II of the book concerns nicotine and cancer, discussing the metabolic fates of (S)-nicotine and its pyrrolic analog beta-nicotine, tobacco-specific nitrosamines, and nicotine and lung cancer. Part III of the book deals with (1) nicotine and reproduction, considering the impact of fetal nicotine exposure on nervous system development and its role in sudden infant death syndrome; (2) measuring fetal exposure to nicotine; and (3) human studies of nicotine replacement during pregnancy. Part IV of the book deals with behavioral toxicity of nicotine, considering abuse liability of nicotine, behavioral toxicology of nicotine, and dependence on and abuse of nicotine replacement medications. Part V, Other Topics, covers nicotine and the gastrointestinal tract, adverse events and prolonged use of nicotine gum and patches, and long-term nicotine therapy. Part VI presents a summary of the risks and benefits of nicotine.
Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “nicotine” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “nicotine” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “nicotine” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •
A Critique of Nicotine Addiction by Hanan Frenk, Reuven Dar; ISBN: 0792372255; http://www.amazon.com/exec/obidos/ASIN/0792372255/icongroupinterna
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Advances in Nicotine Research by Peter P. Rowell, Laurence A. Carr (2001); ISBN: 1401029558; http://www.amazon.com/exec/obidos/ASIN/1401029558/icongroupinterna
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American Psychiatric Association Practice Guideline for the Treatment of Patients With Nicotine Dependence by American Psychiatric Association, APA (1996); ISBN: 0890423083; http://www.amazon.com/exec/obidos/ASIN/0890423083/icongroupinterna
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Analytical Determination of Nicotine and Related Compounds and their Metabolites by J. W. Gorrod (Editor), et al; ISBN: 0444500952; http://www.amazon.com/exec/obidos/ASIN/0444500952/icongroupinterna
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Behavioral Effects of Nicotine: Proceedings by K. Baettig (Editor), Zu Cotine (1978); ISBN: 3805527632; http://www.amazon.com/exec/obidos/ASIN/3805527632/icongroupinterna
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Brain Imaging of Nicotine & Tobacco Smoking by E. F. Domino (Editor) (1995); ISBN: 091618210X; http://www.amazon.com/exec/obidos/ASIN/091618210X/icongroupinterna
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Caffeine and Nicotine (The Drug Abuse Prevention Library) by Richard S. Lee, Mary Price Lee (1998); ISBN: 0823927458; http://www.amazon.com/exec/obidos/ASIN/0823927458/icongroupinterna
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Cigarettes, Nicotine, and Health : A Biobehavioral Approach by Lynn T. Kozlowski (Author), et al (2001); ISBN: 0803959478; http://www.amazon.com/exec/obidos/ASIN/0803959478/icongroupinterna
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Drug Therapy for Smoking Cessation: Is Nicotine Best? by Linda Ferry; ISBN: 1581110502; http://www.amazon.com/exec/obidos/ASIN/1581110502/icongroupinterna
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Effects of Nicotine on Biological Systems (Advances in Pharmacological Sciences) by Franz Adlkofer, Klaus Thurau (Editor) (1991); ISBN: 0817625194; http://www.amazon.com/exec/obidos/ASIN/0817625194/icongroupinterna
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Effects of Nicotine on Biological Systems II (Advances in Pharmacological Sciences) by P. B. S. Clarke (1995); ISBN: 0817650830; http://www.amazon.com/exec/obidos/ASIN/0817650830/icongroupinterna
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Electrophysiological effects of nicotine : proceedings of the International Symposium on the Electrophysiological Effects of Nicotine, Paris (France), 19-20 October 1978; ISBN: 0444801839; http://www.amazon.com/exec/obidos/ASIN/0444801839/icongroupinterna
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Escape from Nicotine Country: How to Stop Smoking Painlessly by James Christopher (1999); ISBN: 1573927511; http://www.amazon.com/exec/obidos/ASIN/1573927511/icongroupinterna
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Fao Specifications for Plant Protection Products: Nicotine and Nicotine Sulphate (1977); ISBN: 9251005524; http://www.amazon.com/exec/obidos/ASIN/9251005524/icongroupinterna
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Focus on Nicotine and Caffeine by David Neuhaus, Robert Perry; ISBN: 0941477991; http://www.amazon.com/exec/obidos/ASIN/0941477991/icongroupinterna
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Focus on Nicotine and Caffeine: A Drug Alert Book by Robert Perry, et al; ISBN: 0516073559; http://www.amazon.com/exec/obidos/ASIN/0516073559/icongroupinterna
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Growing Up Tobacco Free: Preventing Nicotine Addiction in Children and Youths by Barbara S. Lynch (Editor), et al (1994); ISBN: 0309051290; http://www.amazon.com/exec/obidos/ASIN/0309051290/icongroupinterna
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Health Consequences of Smoking, Nicotine Addiction; ISBN: 0160022851; http://www.amazon.com/exec/obidos/ASIN/0160022851/icongroupinterna
490 Nicotine
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Health Consequences of Smoking, Nicotine Addiction: A Report of the Surgeon General; ISBN: 0160237041; http://www.amazon.com/exec/obidos/ASIN/0160237041/icongroupinterna
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Health Consequences of Smoking: Nicotine Addiction a Report of the Surgeon General 1988 by C. Everett Koop (1988); ISBN: 0788123149; http://www.amazon.com/exec/obidos/ASIN/0788123149/icongroupinterna
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Hooked but Not Helpless: Ending Your Love Hate Relationship With Nicotine by Patricia Allison, et al; ISBN: 0962368326; http://www.amazon.com/exec/obidos/ASIN/0962368326/icongroupinterna
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Hooked but Not Helpless: Kicking Nicotine Addiction by Patricia Allison, Jack Yost; ISBN: 0962368377; http://www.amazon.com/exec/obidos/ASIN/0962368377/icongroupinterna
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How to Stop Smoking Permanently: With the New Nicotine Gum by Walter S. Ross; ISBN: 0316757527; http://www.amazon.com/exec/obidos/ASIN/0316757527/icongroupinterna
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How to Use Nicotine Gum by Nina Schneider (Author); ISBN: 0671618539; http://www.amazon.com/exec/obidos/ASIN/0671618539/icongroupinterna
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How to Use Nicotine Gum and Other Strategies to Quit Smoking by Schneider (1989); ISBN: 9990372144; http://www.amazon.com/exec/obidos/ASIN/9990372144/icongroupinterna
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If Only I Could Quit: Recovering from Nicotine Addiction by Karen Casey; ISBN: 0894864386; http://www.amazon.com/exec/obidos/ASIN/0894864386/icongroupinterna
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If You Love Somebody Who Smokes: Confessions of a Nicotine Addict by Cynthia Morgan (1987); ISBN: 0933944144; http://www.amazon.com/exec/obidos/ASIN/0933944144/icongroupinterna
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International Symposium on Nicotine: the Effects of Nicotine on Biological Systems II : the abstracts; ISBN: 3764350873; http://www.amazon.com/exec/obidos/ASIN/3764350873/icongroupinterna
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My Lady Nicotine by James Matthew Barrie (2001); ISBN: 1589633083; http://www.amazon.com/exec/obidos/ASIN/1589633083/icongroupinterna
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New Developments in Nicotine Delivery Systems by Phenningfield (Editor) (1991); ISBN: 9992191015; http://www.amazon.com/exec/obidos/ASIN/9992191015/icongroupinterna
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Nicotine by Agatha Christie; ISBN: 8370231926; http://www.amazon.com/exec/obidos/ASIN/8370231926/icongroupinterna
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Nicotine by Jack E. Henningfield (1992); ISBN: 0685522490; http://www.amazon.com/exec/obidos/ASIN/0685522490/icongroupinterna
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Nicotine (Drug Education Library) by Jenny Rackley, Jennifer Rackley (2002); ISBN: 1590180127; http://www.amazon.com/exec/obidos/ASIN/1590180127/icongroupinterna
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Nicotine (Drug Library) by Judy Monroe; ISBN: 0894905058; http://www.amazon.com/exec/obidos/ASIN/0894905058/icongroupinterna
Books 491
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Nicotine (Drugs, the Straight Facts) by Chelsea House Publications, et al (2003); ISBN: 0791072649; http://www.amazon.com/exec/obidos/ASIN/0791072649/icongroupinterna
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Nicotine Addiction by John Hicks; ISBN: 0761303227; http://www.amazon.com/exec/obidos/ASIN/0761303227/icongroupinterna
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Nicotine Addiction Among Adolescents by Eric F. Wagner (Editor) (2000); ISBN: 0789011700; http://www.amazon.com/exec/obidos/ASIN/0789011700/icongroupinterna
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Nicotine Addiction in Britain; ISBN: 1860161227; http://www.amazon.com/exec/obidos/ASIN/1860161227/icongroupinterna
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Nicotine Addiction: Principles and Management by C. Tracy Orleans (Editor), John Slade (Editor) (1993); ISBN: 0195064410; http://www.amazon.com/exec/obidos/ASIN/0195064410/icongroupinterna
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Nicotine and Cigarettes (Junior Drug Awareness) by Gina De Angelis; ISBN: 0791051757; http://www.amazon.com/exec/obidos/ASIN/0791051757/icongroupinterna
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Nicotine and Public Health by Roberta Ferrence (Editor), et al (2000); ISBN: 0875532497; http://www.amazon.com/exec/obidos/ASIN/0875532497/icongroupinterna
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Nicotine and Related Alkaloids: Absorption, Distribution, Metabolism and Excretion by J. Wahren (Editor), J. W. Gorrod (1993); ISBN: 0412557401; http://www.amazon.com/exec/obidos/ASIN/0412557401/icongroupinterna
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Nicotine and the Tobacco Smoking Habit by D. J. K. Balfour (Editor); ISBN: 0080307795; http://www.amazon.com/exec/obidos/ASIN/0080307795/icongroupinterna
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Nicotine Fit, a Nightmare by D. V. Thomas (1987); ISBN: 0929623002; http://www.amazon.com/exec/obidos/ASIN/0929623002/icongroupinterna
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Nicotine in Psychiatry: Psychopathology and Emerging Therapeutics by Melissa, M.D. Piasecki (Editor), et al; ISBN: 0880487976; http://www.amazon.com/exec/obidos/ASIN/0880487976/icongroupinterna
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Nicotine Jukebox by Marc C. Jacksina (1999); ISBN: 1881168042; http://www.amazon.com/exec/obidos/ASIN/1881168042/icongroupinterna
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Nicotine Management: Air Cigarettes by Alice Morin (1997); ISBN: 0965885402; http://www.amazon.com/exec/obidos/ASIN/0965885402/icongroupinterna
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Nicotine Psychopharmacology: Molecular, Cellular, and Behavioural Aspects (Oxford Science Publications) by S. Wonnacott, et al (1990); ISBN: 0192616145; http://www.amazon.com/exec/obidos/ASIN/0192616145/icongroupinterna
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Nicotine replacement : a critical evaluation; ISBN: 0845151118; http://www.amazon.com/exec/obidos/ASIN/0845151118/icongroupinterna
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Nicotine Replacement: A Critical Evaluation by Ovide F. Pomerleau (Editor), et al (1992); ISBN: 1560242507; http://www.amazon.com/exec/obidos/ASIN/1560242507/icongroupinterna
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Nicotine Safety and Toxicity by Neal L. Benowitz (Editor), Society for Research on Nicotine and Tobacco; ISBN: 0195114965; http://www.amazon.com/exec/obidos/ASIN/0195114965/icongroupinterna
492 Nicotine
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Nicotine Water to Heroin by Shibani Roy, S. H. M. Rizvi; ISBN: 8170182972; http://www.amazon.com/exec/obidos/ASIN/8170182972/icongroupinterna
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Nicotine, Caffeine and Social Drinking: Behaviour and Brain Function by Jan Snel (Editor), et al; ISBN: 9057022184; http://www.amazon.com/exec/obidos/ASIN/9057022184/icongroupinterna
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Nicotine, Smoking, and the Low Tar Programme (Oxford Medical Publications) by Sir Peter Froggatt, et al (1991); ISBN: 019261729X; http://www.amazon.com/exec/obidos/ASIN/019261729X/icongroupinterna
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Nicotine: An Old-fashioned Addiction (Encyclopedia of Psychoactive Drugs); ISBN: 0222012153; http://www.amazon.com/exec/obidos/ASIN/0222012153/icongroupinterna
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Nicotine: An Old-Fashioned Addiction (Encyclopedia of Psychoactive Drugs. Series 1) by Solomon H. Snyder (Editor), et al; ISBN: 0877547513; http://www.amazon.com/exec/obidos/ASIN/0877547513/icongroupinterna
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Nicotine: Subject Reference and Research Guide by Selma C. Elkton (1987); ISBN: 0881645400; http://www.amazon.com/exec/obidos/ASIN/0881645400/icongroupinterna
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Pharmacology of Nicotine: Proceedings, Satellite Symposium of the Tenth International Congress of Pharmacology, Gold Coast, Queensland, Australia, Se (Icsu Press Symposium Series, No. 9.) by J. Michael/ Rand, M. J./ Thurau, Klaus/ International Congress of Pharmacology 1987 Sydney, N.S.W.) International Symposium on the Pharmacology of Nicotine / Rand, et al; ISBN: 185221094X; http://www.amazon.com/exec/obidos/ASIN/185221094X/icongroupinterna
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Quit Smoking: With the Nicotine Phaseout Programme by Chris Steele; ISBN: 1874082022; http://www.amazon.com/exec/obidos/ASIN/1874082022/icongroupinterna
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Reduced Tar and Nicotine Cigarettes: Smoking Behavior and Health by Dean R. Gerstein (Editor); ISBN: 0309032466; http://www.amazon.com/exec/obidos/ASIN/0309032466/icongroupinterna
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Risks Associated With Smoking Cigarettes With Low Machine-Measured Yields of Tar and Nicotine by Donald R. Shopland (Editor) (2003); ISBN: 0756726751; http://www.amazon.com/exec/obidos/ASIN/0756726751/icongroupinterna
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Smoke Screen: Psychological Disorders Related to Nicotine Use (Encyclopedia of Psychological Disorders) by Daniel Partner, et al; ISBN: 0791049582; http://www.amazon.com/exec/obidos/ASIN/0791049582/icongroupinterna
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Smoker: Self-Portrait of a Nicotine Addict by Ellen Walker; ISBN: 0062553909; http://www.amazon.com/exec/obidos/ASIN/0062553909/icongroupinterna
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Stop Smoking with Patricia Allison: A Personal Program for Treating Nicotine Addiction by Patricia Allison (1998); ISBN: 0966883608; http://www.amazon.com/exec/obidos/ASIN/0966883608/icongroupinterna
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The 12 Tiger Steps Out of Nicotine Addiction: A Step Study Guide for Nicotine Addiction Recovery by Paul Lagergren, Dug Waggoner (Illustrator) (1995); ISBN: 0964549247; http://www.amazon.com/exec/obidos/ASIN/0964549247/icongroupinterna
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The 2002 Official Patient's Sourcebook on Nicotine Dependence: A Revised and Updated Directory for the Internet Age by Icon Health Publications (2002); ISBN:
Books 493
0597832595; http://www.amazon.com/exec/obidos/ASIN/0597832595/icongroupinterna •
The aetiology of psychoactive substance use : a report and critically annotated bibliography on research into the aetiology of alcohol, nicotine, opiate and other psychoactive substance use by C. Fazey; ISBN: 9231015087; http://www.amazon.com/exec/obidos/ASIN/9231015087/icongroupinterna
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The Biology of Nicotine Dependence - Symposium No. 152 by CIBA Foundation Symposium (Author); ISBN: 0471926884; http://www.amazon.com/exec/obidos/ASIN/0471926884/icongroupinterna
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The Biology of Nicotine: Current Research Issues by Patrick M. Lippiello, Allan C. Collins; ISBN: 0881678600; http://www.amazon.com/exec/obidos/ASIN/0881678600/icongroupinterna
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The Clinical Management of Nicotine Dependence by James A. Cocores (Editor); ISBN: 0387974644; http://www.amazon.com/exec/obidos/ASIN/0387974644/icongroupinterna
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The Clinical Management of Nicotine Dependence (1991); ISBN: 3540974644; http://www.amazon.com/exec/obidos/ASIN/3540974644/icongroupinterna
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The Ftc Cigarette Test Method for Determining Tar, Nicotine & Carbon Monoxide Yields of U. S. Cigarettes by Donald R. Shopland (Editor) (1996); ISBN: 0788146149; http://www.amazon.com/exec/obidos/ASIN/0788146149/icongroupinterna
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The Management of Nicotine Dependency by Renee Bittoun; ISBN: 0864331037; http://www.amazon.com/exec/obidos/ASIN/0864331037/icongroupinterna
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The Nicotine Trick: The Foolproof, Guaranteed Way to Kick the Habit by Neil Casey (2003); ISBN: 1843580519; http://www.amazon.com/exec/obidos/ASIN/1843580519/icongroupinterna
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The Psychopharmacology of Nicotine by David J. K. Balfour (Author), Maureen E. M. Benwell (Author); ISBN: 0521479355; http://www.amazon.com/exec/obidos/ASIN/0521479355/icongroupinterna
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This Is Nicotine by Karen Farrington (2002); ISBN: 1860744192; http://www.amazon.com/exec/obidos/ASIN/1860744192/icongroupinterna
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Thomas's New Nicotine Chewing Gum Home Recipe by Thomas K. Meredith; ISBN: 0966105613; http://www.amazon.com/exec/obidos/ASIN/0966105613/icongroupinterna
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Tobacco and Nicotine Drug Dangers (Drug Dangers (Cloth)) by Joan Vos Macdonald, Joan Vos Macdonald; ISBN: 0766013170; http://www.amazon.com/exec/obidos/ASIN/0766013170/icongroupinterna
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Tobacco Smoking and Nicotine: A Neurobiological Approach (Advances in Behavioral Biology, Vol 31) by William R. Martin, et al (1987); ISBN: 0306426110; http://www.amazon.com/exec/obidos/ASIN/0306426110/icongroupinterna
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Treating Nicotine Addiction by Vincent C. Pletcher, et al (1991); ISBN: 0894867156; http://www.amazon.com/exec/obidos/ASIN/0894867156/icongroupinterna
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Twelve Steps for Tobacco Users: For Recovering People Addicted to Nicotine by Jeanne F, Jeanne E (1984); ISBN: 0894862294; http://www.amazon.com/exec/obidos/ASIN/0894862294/icongroupinterna
494 Nicotine
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Up in Smoke: The Nicotine Challenge in Recovery (#5413B) by Tom O'Connell (1990); ISBN: 0894866451; http://www.amazon.com/exec/obidos/ASIN/0894866451/icongroupinterna
The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “nicotine” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:11 •
1975 Symposium "Nicotine and Carbon Monoxide": presented by the Tobacco and Health Research Institute and the Kentucky Tobacco Research Board, November 17, 18, 1975, University of Kentucky, Lexington, Kentucky. Author: Symposium "Nicotine and Carbon Monoxide", University of Kentucky, 1975.; Year: 1973; [Lexington, Ky.: University of Kentucky, 1976?]
•
Defining and addressing addictions: a psychological and sociocultural perspective: with an emphasis on nicotine and alcohol as prototypic, gateway drugs, and addictive substances Author: Christen, Joan A.; Year: 1981; Indianapolis, Ind.: Indiana Univ. School of Dentistry/Dept. of Preventive and Community Dent. (1121 W. Michigan St., Indianapolis, IN 46202-5186), c1990
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Monograph on the pharmacology and toxicology of nicotine Author: Cohen, A. J.; Year: 9999; London: Tobacco Advisory Council, 1981
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Public health cigarette amendments of 1971. Hearings. United States Senate, Ninetysecond Congress, second session, on S. 1454 to amend the Federal cigarette labeling and advertising act to require the Federal Trade Commission to establish acceptable levels of tar and nicotine content of cigarettes, February 1, 3, and 10, 1972. Author: United States. Congress. Senate. Committee on Commerce. Consumer Subcommittee.; Year: 1972; Washington, U. S. Govt. Print. Off., 1972
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Reduced tar and nicotine cigarettes: smoking behavior and health Author: Gerstein, Dean R.; Year: 1978; Washington, D.C.: National Academy Press, 1982; ISBN: 0309032460
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Some central effects of nicotine as correlated to the pharmacokinetics of nicotine in mice and rats Author: Mansner, Raija.; Year: 1964; Helsinki: [s.n.], 1978
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Studies on the distribution, biotransformation and toxicity of nicotine in mice of different ages Author: Stålhandske, Torbjörn.; Year: 1959; Stockholm: [s.n.], 1970
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Symposium on the Effects of Nicotine on Nervous Functions Author: Swedish Tobacco Company. Medical Advisory Board.; Year: 1982; Stockholm: The Board, 1980
11
In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.
Books 495
Chapters on Nicotine In order to find chapters that specifically relate to nicotine, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and nicotine using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “nicotine” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on nicotine: •
Use of Nicotine and Tobacco in Colitis Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 99-101. Contact: Available from B.C. Decker Inc. 20 Hughson Street South, P.O. Box 620, L.C.D. 1 Hamilton, Ontario L8N 3K7. (905) 522-7017 or (800) 568-7281. Fax (905) 522-7839. Email:
[email protected]. Website: www.bcdecker.com. PRICE: $129.00 plus shipping and handling. ISBN: 1550091220. Summary: This chapter on the use of nicotine and tobacco for treating colitis is from the second edition of a book devoted to the details of medical, surgical, and supportive management of patients with Crohn's disease (CD) and ulcerative colitis (UC), together known as inflammatory bowel disease (IBD). Previous epidemiological observations suggested a beneficial effect of smoking in patients with UC and led to the investigational use of nicotine as a therapeutic agent. Ulcerative colitis is a disease of nonsmokers. Treatment with transdermal (skin patch) nicotine appears to be effective for active UC at the highest tolerated dose of nicotine (22 to 25 milligrams every 24 hours ) but it is not effective at low doses as maintenance therapy. Uncontrolled pilot studies showed that nicotine enemas may be of clinical benefit for left-sided colitis. Controlled studies with topical nicotine treatment (enemas or delayed-release oral capsules) are awaited. Adverse reactions are a limiting factor for long-term transdermal nicotine therapy, particularly in life-long nonsmokers, whereas nicotine enemas have low systemic absorption and are well tolerated. At present, transdermal nicotine is not a first-line therapy for UC and should be reserved for patients who have failed other medical therapies. Although smoking is reported to be beneficial for the course of UC, prescription of smoking must be tempered by the significant and potentially fatal consequences of its effects on other body systems; in their clinical practice, the authors strongly discourage patients from smoking. 1 table. 9 references.
•
Adherence to Treatment for Nicotine Dependence Source: in Handbook of Health Behavior Change. Shumaker, S.A. Schron, E.B. Ockene, J.K; McBee, W.L. eds. New York, NY, Springer Publishing Company, pp. 137-165, 1998. Contact: Springer Publishing Company, 536 Broadway, New York, NY 10012. Summary: Adherence to Treatment for Nicotine Dependence, a chapter in The Handbook of Health Behavior Change, discusses techniques derived from the Cognitive Social Learning Theory for promoting adherence of adults in smoking cessation interventions. The chapter (1) presents individual and population perspectives on adherence relevant to smoking prevention; (2) presents a broadened definition of adherence; (3) discusses a proposed stepped-care matching model of adherence that can
496 Nicotine
be used in smoking cessation interventions; (4) describes specific applications of the stepped care-approach for smoking cessation; and (5) discusses issues that cut across the levels of stepped care, including ethnic/minority issues and comorbidity. Surveys have shown that despite a steady decrease in the overall percentage of smokers in the United States population from 1965 to 1990 and the variety of clinical and public health interventions available to help smokers quit, population smoking cessation rates during the 1990's have leveled off. The static smoking cessation rates are due to a number of factors that can be construed as related to adherence issues including (1) many smokers not adequately adhering to treatment components known to be effective; (2) a lack of breakthrough treatments that could be more effective at meeting certain smokers' needs; (3) appropriate interventions not being proactively delivered to the majority of smokers who are not currently motivated to quit; and (4) intervention delivery systems, economic, and other societal factors presenting barriers to access to optimal treatment. These factors are, therefore, regarded as making it less likely that smokers will be motivated to participate long-term in smoking cessation programs. This situation indicates that both individual and population or public health perspectives are relevant to a broader framework for conceptualizing adherence. The definition of adherence is, therefore, broadened to mean the degree to which (1) an interventionist and/or the treatment delivery system adheres to a specific protocol, and/or (2) the extent to which the treatment is proactively delivered to and successfully reaches a specific population, such as an underserved population of smokers who are not motivated to consider cessation. The stepped-care model incorporates this wider definition of adherence. For a smoker who is ready to quit, the model has three broad levels of care related to type, intensity, and cost of the intervention: (1) Minimal, based on self-change and/or selfhelp; (2) moderate, consisting of brief (often tailored) counseling plus followup; and (3) maximal, based on specialized formal clinical treatment with both outpatient and inpatient options. Moderate and maximal intensity level interventions (levels 2 and 3) are considered to be more appropriate for ethnic or minority groups than minimal (level 1) interventions, unless self-help materials are specifically targeted to the groups. •
Harm Reduction, Nicotine, and Smoking Source: in Harm Reduction: Pragmatic Strategies for Managing High-risk Behaviors. Marlatt, G.A. ed. New York, NY, Guilford Press, pp. 122-144, 2000. Contact: Guilford Press, 72 Spring Street, New York, NY 10012. INTERNET/EMAIL: http://www.guilford.com. Summary: Harm Reduction, Nicotine, and Smoking, a chapter in Harm Reduction: Pragmatic Strategies for Managing High-risk Behaviors, explores how harm reduction approaches can be applied to the addictive use of nicotine, with a primary focus on smoking. The chapter does not attempt to review all possible interventions but rather discusses both the potential advantages and risks of harm reduction strategies. The chapter opens with a brief history of tobacco use in the United States. It is commonly acknowledged now that tobacco users have difficulty quitting once they have begun regular use. In spite of efforts in the past several decades to reduce tobacco use in the United States, a decline of only about 16 percent has been achieved since 1965. Any discussion of harm reduction and smoking in particular necessitates an understanding of the basic relationship between health harm and smoking behavior. While nicotine is the addictive agent in tobacco products, it is not the nicotine in cigarettes that causes most of the health problems associated with smoking. Harm reduction strategies for smoking and other use of tobacco products can be categorized in several ways. In a discussion of nicotine use, four general areas of potential change are considered: (1)
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Restricting access, (2) altering how people use nicotine, (3) changing the nature of consumer products that contain nicotine, and (4) replacing nicotine. In a general sense, the trend to label those who attempt to quit smoking and do not succeed as treatment failures must be revised and an attempt made to study the processes of change that have the potential to lead to better health outcomes. Failure in an initial harm reduction effort directed at tobacco use may be motivational for a subsequent cessation attempt. •
Nicotine Dependence Among Blacks and Hispanics Source: in Nicotine Addiction: Principles and Management. Orleans, C.T. Slade, J. eds. New York, NY, Oxford University Press, pages 350-364, 1993. Contact: Oxford University Press, 200 Madison Avenue, New York, NY 10016. Summary: Nicotine Dependence Among Blacks and Hispanics, a book chapter in Nicotine Addiction: Principles and Management, notes that minority populations are edging ahead of their white counterparts in prevalence of adult tobacco use and risk of tobacco-related disease. Both blacks and Hispanics suffer from long-standing disparities in knowledge of smoking health risks and access to health care as compared to whites. Research shows startling increases in daily level of cigarette consumption by Hispanic adults. A lower rate of cigarette consumption among blacks is offset by a predilection for high tar/nicotine, mentholated cigarettes. Sociodemographic factors related to smoking among blacks are similar to those for the United States population as a whole. Demographic factors related to smoking status are similar for Hispanics and whites, though smoking status among Hispanics varies with ethnic subgroup and level of acculturation. Compared with whites, blacks and Hispanics are less likely to (1) have information about cancer prevention, (2) associate tobacco use with cancer risk, and (3) seek physician advice. Extensive tobacco marketing campaigns targeting minorities create major barriers to cessation and prevention. Insidious advertising occurs on the streets of minority neighborhoods in the form of billboards. Teens are especially vulnerable to advertising, and minority youth are less equipped to resist it. Determinants of quitting for minorities much like those within the general population. New studies show a stronger desire to quit among blacks than whites, although blacks are less likely than whites to quit smoking regardless of socioeconomic status or demographic factors. Quitting barriers include (1) low income, (2) employment status, (3) limited access to health care, (4) weaker social support, and (5) stronger environmental influences to relapse. Many smoking cessation programs are available, but few are tailored to the groups at highest risk. Appealing to distinct market segments within minority communities is essential for effective communications. A few smoking control interventions for blacks and Hispanics currently offer culturally appropriate materials.
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Effects of Nicotine During Pregnancy Source: in Nicotine and Public Health. Ferrence, R. Slade, J. Room, R. Pope, M. eds. Washington, DC, American Public Health Association, pp. 77-92, 2000. Contact: American Public Health Association, 800 I Street, NW., Washington, DC 200013710. Summary: Effects of Nicotine During Pregnancy, a chapter in Nicotine and Public Health, presents an assessment of the potential role of nicotine in producing poor obstetrical outcomes. The author compares major adverse fetal outcomes associated with maternal smoking during pregnancy (i.e., spontaneous abortion, low birthweight, and sudden infant death syndrome with the occurrence of similar events associated
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with the administration of nicotine to pregnant animals. A review of the pharmacodynamic effects of nicotine sheds light on mechanisms that might mediate the effects of cigarette smoking on poor fetal outcomes. Implications of this data are related to nicotine replacement therapy. Available data suggest that nicotine produces fetal hypoxemia by reducing placental blood flow. Dose and rate of delivery of nicotine, as well as maternal catecholamine release, are important determinants of these effects. While nicotine may be harmful during pregnancy, the risk/benefit profile of nicotine replacement products seems favorable when compared with continued cigarette smoking. Nicotine replacement products avoid exposure of the fetus to carbon monoxide and other compounds. Furthermore, nicotine replacement products are designed to deliver less nicotine at a slower rate than nicotine delivered by smoking. Until definitive answers are known, it is important to consider the overall nicotine exposure produced by various nicotine replacement therapies compared with smoking. •
Impact of Fetal Nicotine Exposure on Nervous System Development and Its Role in Sudden Infant Death Syndrome Source: in Nicotine Safety and Toxicity. Benowitz, N.L. ed. New York, NY, Oxford University Press, pp. 89-97, 1998. Summary: The Impact of Fetal Nicotine Exposure on Nervous System Development and Its Role in Sudden Infant Death Syndrome, a chapter in Nicotine Safety and Toxicity, notes that animal models of fetal nicotine exposure allow the separation of multiple factors producing structural and functional abnormalities in the offspring of women who smoke. These models also enable researchers to ascertain the specific roles of nicotine itself. Use of continuous infusions of nicotine throughout gestation shows that nicotine is a neuroteratogen, resulting in the arrest of cell replication and long-term shortfalls of synaptic activity. These actions are noted at doses below the threshold for growth retardation or other general toxicity markers. Physiological defects associated with sudden infant death syndrome (SIDS) can be reproduced in animals exposed to nicotine prenatally, providing a mechanistic explanation for the epidemiological association of tobacco use with SIDS. While a smoker can be encouraged to refrain from smoking and to substitute nicotine to avoid fetal damage associated with the hypoxic ischemic component of smoking, many of the basic injurious events may still occur because significant damage can be caused by nicotine itself. Standard developmental indices of safety, such as fetal or neonatal weight, are inappropriate because the threshold for impaired nervous system development lies below that for growth suppression. Nicotine replacement is not viewed as a panacea to avoid neurobehavioral damage or SIDS in the offspring of smoking mothers.
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Measuring Fetal Exposure to Nicotine Source: in Nicotine Safety and Toxicity. Benowitz, N.L. ed. New York, NY, Oxford University Press, pp. 99-106, 1998. Summary: Measuring Fetal Exposure to Nicotine, a chapter in Nicotine Safety and Toxicity, indicates that nicotine and cotinine levels can be accurately measured in the hair of neonates and their mothers. With the availability of smoking cessation aids such as nicotine replacement therapy, physicians are presented with an opportunity to help pregnant women quit smoking. However, delivering nicotine to pregnant women presents an ethical dilemma. Smoking cessation is more probable if nicotine replacement therapy is used; however, nicotine can have adverse effects on fetuses. The ethical dilemma can, however, be resolved if an accurate level of maternal self-administration of nicotine can be obtained. Provided that an accurate level is obtained prior to
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administration of nicotine replacement therapy, and nicotine is delivered in doses that do not exceed the maternal self-administered amounts, the most ethical treatment can be to administer nicotine because the chances of success in smoking cessation are much greater if a nicotine replacement therapy is used. Because hair can be assessed for nicotine levels over time, hair measurement of nicotine and cotinine levels is an excellent method for obtaining the baseline values needed to determine the amount of nicotine advisable to deliver as part of a smoking cessation program. •
Human Studies of Nicotine Replacement During Pregnancy Source: in Nicotine Safety and Toxicity. Benowitz, N.L. ed. New York, NY, Oxford University Press, pp. 107-116, 1998. Summary: Human Studies of Nicotine Replacement During Pregnancy, a chapter in Nicotine Safety and Toxicity, reviews the known effects and potential toxicity of nicotine in pregnancy, based on studies of nicotine administration in animals and humans. Smoking has not been consistently associated with congenital malformation in the developing fetus in animal or human studies, but it is associated with an increased risk of spontaneous abortion. Fetal growth restriction is strongly associated with smoking during pregnancy. Impaired growth is dose-dependent and correlates well with serum cotinine concentrations. Nicotine may play a role in growth restriction, preterm labor, and stillbirth by reducing maternal uteroplacental blood flow and oxygen delivery. Nicotine may influence fetal behavior such as fetal breathing, movements, and tone. Maternal smoking is associated with placental abruption and placenta previa, which contribute to the increased prematurity and fetal death rates. Nicotine replacement therapy can be considered reasonably safe only to the extent that it does not exceed the physiological perturbations or fetoplacental nicotine exposure of the pre-existing smoking behavior it treats. Efficacy in pregnancy currently cannot be addressed. Clearly, nicotine exposure may be harmful during pregnancy and, while nicotine replacement therapy is probably less harmful than smoking, there is no safe dose of nicotine during pregnancy. Therefore, efficacy should be measured by proven reduction in exposure of mother and fetus to nicotine.
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Principles of Teratology and an Update on Nicotine, Ethanol and Caffeine Abuse Source: in Guide to Reproduction: Social Issues and Human Concerns. Pollard, I. Cambridge, England, Cambridge University Press, pp. 353-375, 1994. Contact: Cambridge University Press, 40 West 20th Street, New York, NY 10011-4211. Summary: Principles of Teratology and an Update on Nicotine, Ethanol and Caffeine Abuse, a chapter in A Guide to Reproduction: Social Issues and Human Concerns, evaluates the preventable morphological, functional, and behavioral effects of maternal and paternal drug abuse on the fetus, neonate, or child. The time in gestation during which the embryonic/fetal development is disturbed determines its susceptibility to teratogenic agents. Other important factors include the (1) specific agent causing the disturbance, (2) dose and duration of exposure to the agent, (3) genetic susceptibility of the developing offspring, (4) physiological status of the mother, and (5) absorption routes. The critical period of intrauterine development is that time during development at which the embryo or fetus has the greatest sensitivity to a particular stressful influence. The chapter reviews specific effects of nicotine, ethanol, and caffeine exposure. Maternal smoking has been strongly implicated in low birthweight, spontaneous abortion, early fetal death, increased risk of malformations, and long-term defects of growth and behavioral development. Paternal smoking has also been
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associated with adverse effects on the fetus. The effects of maternal alcohol consumption during pregnancy on the fetus include central nervous system dysfunctions, prenatal loss, fetal growth retardation, and developmental defects. Caffeine consumption may reduce fertility in women. Consumption during pregnancy may increase the risk of miscarriage, prematurity, intrauterine growth retardation, and lower birthweight. Caffeine may potentiate the adverse reproductive effects of other drugs, including alcohol and tobacco. •
Treating Nicotine Addiction in High-risk Groups and Patients With Medical Comorbidity Source: in Nicotine Addiction: Principles and Management. Orleans, C.T. Slade, J. eds. New York, NY, Oxford University Press, pp. 279-309, 1993. Contact: Oxford University Press, 198 Madison Ave, New York, NY 10016-4314. INTERNET/EMAIL: http://www.oup-usa.org. Summary: Treating Nicotine Addiction in High-risk Groups and Patients With Medical Co-morbidity, a chapter in Nicotine Addiction: Principles and Management, presents results of smoking cessation interventions delivered to patients with four separate and quite distinct medical conditions: (1) Pregnancy, (2) cardiovascular disease, (3) chronic obstructive pulmonary disease, and (4) cancer. These conditions are all linked by a common concern about present and potential future damage due to cigarette smoking, but the style and context of the patient's interactions with the health care system are vastly different. Special issues in treating pregnant smokers include the health consequences of smoking during pregnancy, smoking prevalence during pregnancy, interventions during pregnancy, and essential elements of treatment programs for pregnant women. Individuals who are pregnant or who have developed major tobaccorelated illness are more likely than the general population to quit smoking and to remain abstinent. It is likely that a part of this increased cessation is due to the greater motivation provided by their health condition and that a part is due to the increased intensity of intervention efforts delivered by the health care system because of their condition. Changes in the environment within which the smoker lives and works, such as restrictions on where smoking is allowed, are currently thought to be a substantial reason why smoking prevalence is declining. These general environmental changes may also influence cessation among high-risk smokers, and they may interact with the cessation interventions delivered to those smokers to increase the rate of successful cessation.
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Nicotine Stimulates Human Pregnant Uterus in Vitro Source: in Smoking and Health 1987. Aoki, M. Hisamichi, S. Tominaga, S. eds. New York, NY, Elsevier Science Publishing Company, International Congress Series no. 780, pp. 743-746, 1988. Contact: Elsevier Science, Inc., 655 Avenue of the Americas, New York, NY 10010-5107. Summary: Researchers in Singapore studied the effect of nicotine on strips of human pregnant and nonpregnant myometrium in vitro to identify a direct relationship, if any, of nicotine on the uterus. Specimens of myometrium from the transverse incision (in the lower uterine segment) were obtained at elective caesarean sections performed at term. A total of 22 muscle strips were dissected out from 10 specimens. Nine nonpregnant human myometrium were obtained from sex reassignment operations; a total of 24 strips were dissected out from these. In addition, adjacent strips from the same specimens were mounted concurrently as control for every experiment. Pure nicotine
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was dissolved in normal saline before being added to the organ bath. Both pregnant and nonpregnant uteri were estimated by all four concentrations of nicotine tested. In all the uterine strips that were stimulated, nicotine increase tone, intensity, and the frequency of contraction markedly. The results may suggest that the pregnant uterus is more susceptible to the contractile action of nicotine than the nonpregnant uterus. Once the contraction to nicotine had been established in a given strip, the same concentration of nicotine was repeated 30 minutes later after adding phentolamine, an alphaadrenoceptor blocking agent. When noradrenaline was added to four strips of pregnant and nonpregnant myometrium, uterine activity contracted and increased uterine activity in all the uterine strips tested, confirming the known stimulant activity of the drug. Researchers conclude that since reduced fecundity had been reported to occur among smoking women, it is tempting to speculate that the nicotine-induced contraction of the nonpregnant uterus that was observed in the study may partly explain the reduction in fertility among such women. 1 figure, 1 table, 4 references. •
Effect of Tar, Nicotine, and Carbon Monoxide on Pregnancy Outcome Source: in Smoking and Reproductive Health. Rosenberg, M.J. ed. Littleton, MA, PSG Publishing Company, Inc., pp. 117-123, 1987. Contact: PSG Publishing Company, Inc., Littleton, MA. Summary: Effect of Tar, Nicotine, and Carbon Monoxide on Pregnancy Outcome, a chapter in Smoking and Reproductive Health, examines the risk for low birthweight posed by different average daily exposures to tar, nicotine, and carbon monoxide (as a group), as well as number of cigarettes. Data came from the 1980 National Natality Survey (NNS) of the National Center for Health Statistics. This was a mailed follow-back survey of mothers, hospitals, and other medical sources identified on birth certificates for 9,941 liveborn infants. Low-birthweight infants were oversampled to support detailed analyses of high-risk infants. Researchers linked information from birth certificates to the questionnaire mailed to each married mother, which requested information about prenatal health practices, such as drinking and smoking, prenatal medical visits, and other demographic characteristics. This analysis included 3,751 married white mothers of singleton infants, among them 1,116 smokers for whom cigarette component values could be derived. Researchers grouped exposure to cigarette components into four levels, and examined them for three time periods (before, after, and throughout pregnancy). The data analysis controlled for various maternal factors. Exposure levels were derived from the quartile distribution of average daily exposure to cigarette toxins for 922 smokers who did not stop during pregnancy. Risk of low birthweight was estimated for each level of exposure compared with that of nonsmokers. To examine the effect of reducing smoking during pregnancy, researchers determined risk of low birthweight for the period after conception but before pregnancy was confirmed, for the period after pregnancy was confirmed, and for both periods combined. Results showed a dose-response relationship of exposure to cigarette toxins with relative risk of low birthweight among white, married mothers of liveborn, singleton infants. There was an increased risk of low birthweight for women who reported smoking as few as seven cigarettes per day. The estimates of relative risk increased directly with exposure to cigarette toxins above this level. About 30 percent of the women smoked at the time of conception, 5 percent quit after pregnancy was confirmed, and 25 percent smoked throughout pregnancy. Mean daily exposure to tar, nicotine, and carbon monoxide decreased after pregnancy was confirmed because women either reduced the number of cigarettes smoked or switched to less potent brands. The study found no evidence that smoking early in pregnancy was more
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harmful than smoking later in pregnancy. Mothers who quit smoking during pregnancy were no more likely to have low-birthweight infants than nonsmoking mothers. •
Amino Acid Uptake by Human Placenta: Alterations by Nicotine and Tobacco Smoke Components and Their Implications on Fetal Growth Source: in Developmental Neuroscience: Physiological, Pharmacological and Clinical Aspects: Proceedings of the 5th International Meeting of the International Society for Developmental Neuroscience Held in Chieti, Italy, Jun e 24-28, 1984. Caciagli, F. Giacobini, E. Paoletti, R. eds. New York, NY, Elsevier Science Publishers, Symposia of the Giovanni Lorenzini Foundation, Volume 20, pp. 137-140, 1984. Contact: Elsevier Science, Inc., P.O. Box 945, Madison Square Station, New York, NY 10160-0757. Summary: A researcher discusses the effects of nicotine and tobacco smoke components on amino acid uptake by human placenta and the consequences for feta l growth. The first section reviews evidence that maternal smoking is associated with reduced birthweight and that smoking-related low birthweight is due to fetal growth retardation rather than preterm delivery, and outlines the processes involved in the placental transfer of essential amino acids from the maternal circulation to the fetal blood. The second section describes findings concerning the effect of nicotine on human placental acetylcholine (ACh) and th e regulation of amino acid transport in placenta and discusses the regulation of placental ACh release and amino acid transport by methionine enkephalin and related peptides. The third section describes the nature of the inhibition of amino acid uptake by nicotine, morphine, cocaine, and tobacco gases. The fourt h section discusses the relationship between the placental cholinergic system and maturation of placental villi. Overall, the evidence indicates that maternal smoking may subject the fetus to partial amino acid deficits caused by decreasing their uptake by the trophoblast and their transfer from the trophoblast to fetal circulation. Data from experiments with isolated human placental tissue show that nicotine decreases the uptake of aminoisobutyric aci d (AIB), possibly by increasing the release of excess endogenous ACh or by direct antagonist effect, and it also decreases the uptake of acidic (aspartic) and basic (lysine) amino acids. In the fetus, hypoxia due to maternal smoking appears to damage endothelial cells and thereby interferes with ACh-induced relaxation of placental vasculature. This effect coupled with the ability of nicotine to release biogenic amines increases resistance to umbilical blood flo w and decreases passive transfer of amino acids from the trophoblast into the fetal circulation. 13 references.
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CHAPTER 8. MULTIMEDIA ON NICOTINE Overview In this chapter, we show you how to keep current on multimedia sources of information on nicotine. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.
Video Recordings An excellent source of multimedia information on nicotine is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “nicotine” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find video productions, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Videorecording (videotape, videocassette, etc.).” Type “nicotine” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on nicotine: •
Impotence and Diabetes Source: Los Angeles, CA: National Health Video, Inc. 1999. (videocassette). Contact: Available from National Health Video, Inc. 12021 Wilshire Blvd., Suite 550, Los Angeles, CA 90025. (800) 543-6803. Fax (310) 477-8198. E-mail:
[email protected]. PRICE: $89.00 plus shipping and handling. Summary: This patient education videotape program reviews the problem of erectile dysfunction (impotence) and diabetes mellitus. The program defines erectile dysfunction (ED) as the consistent inability to get and maintain an erection. The program first explores the physiology of erections (how they happen), including the need for mental and physical stimulation, nerve impulses in the brain, and responses in muscles, fibrous tissues, and veins and arteries. The program offers a diagram and the use of a balloon to describe how an erection happens, the anatomy of the corpera cavernosa, and the role of nitrous oxide as a neurochemical transmitter. Age is noted as a factor in ED, and men with diabetes tend to develop ED 10 to 15 years earlier than
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men who do not have diabetes. The program notes that psychological factors (stress, depression, guilt, and performance anxiety) can cause 10 to 15 percent of ED; a series of self test questions are included for viewers to determine if psychological factors may play a role in their own ED. For men with diabetes, nerve damage (peripheral neuropathy) is the most likely culprit for causing ED; damage to the blood vessels (atherosclerosis) is another cause. Poor blood glucose control is the most important factor in both of these problems. The program includes a section noting the impact of drugs (including alcohol and nicotine) on ED. The program outlines the steps in diagnosing erectile problems, including first admitting that there is a problem, talking with a doctor, undergoing diagnostic tests, and participating in treatment. The final section reviews treatment options, reiterating the importance of good blood glucose control and describing the use of drug therapy (Viagra), vacuum erectile systems, self injection, and surgery (blood vessel repair and penile implants). The program includes drawings, graphics, and footage of patients and their physicians through the diagnosis and treatment processes. •
The trouble with tobacco Source: Niles, IL: United Learning. 1996. 1 videotape (10 minutes, VHS), 1 teacher's guide (14 pp.). Contact: Available from United Learning, 6633 West Howard Street., P.O. Box 48718, Niles, IL 60714. Telephone: (800) 424-0362 / fax: (708) 647- 0918). $79.50 plus shipping and handling. Summary: This videotape is designed for use with preteens. It discussed why people smoke, medical and other problems associated with tobacco use, and how nicotine affects the brain's chemistry. The teacher's guide contains a program overview, suggested activities, and a transcript of the video.
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Right Choice Source: Santa Cruz, CA: Tobacco Education Clearinghouse of California. 1996. (videocassette). Contact: Available from Tobacco Education Clearinghouse of California/ETR Associates. P.O. Box 1830, Santa Cruz, CA 95061-1830. (831) 438-4822. TDD (831) 4610205. Fax (831) 438-3618. PRICE: $5.00 plus shipping and handling. Item number J333. Summary: This videotape program encourages teens to avoid smokeless tobacco (ST) use, or to quit if they are already users. The program features teenagers, both as narrators and interviewees, under a background of rock music, explaining that ST is addictive, unhealthy, and dangerous. The program also interviews a dental surgeon, a rodeo stock contractor, a young rodeo rider, and a stock dog trainer, who tell of their experiences with ST. Along with the teenagers interviewed, these people discuss the realities of health complications and the social hazards of ST use. The program focuses on the immediate consequences, such as aesthetics and hygiene, and the longer term consequences, such as the risks for oral and other cancers, surgery, and tooth loss. The program reinforces the concept of nicotine addiction and how hard it is to quit a nicotine habit. The program includes color photographs of the mouths, gingiva, and teeth of people with ST related problems. Another section describes how advertising and peer pressure can work to induce young people to try ST. The program concludes with a toll free number for viewers who want more information or help in quitting (800844-CHEW).
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Smokeless Tobacco: Is It Worth the Risk? Source: Alexandria, VA: American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS). 199x. (videocassette). Contact: Available from American Academy of Otolaryngology: Head and Neck Surgery (AAO-HNS). Order Fulfillment, One Prince Street, Alexandria, VA 22314-3357. (703) 836-4444. Fax (703) 683-5100. PRICE: $15.00 each (members); $20.00 (nonmembers); plus shipping and handling. Item Number 4763355. Summary: This videotape program, targeted at adolescent males, reminds viewers of the dangers of smokeless tobacco. The program opens with footage of various major league baseball games, accompanied by upbeat music, as the narrator, Mel Adams, describes baseball as a great American tradition. The narration continues to describe the use of tobacco as another not-so-great American tradition and the evolution from smoking to smokeless tobacco. The program interviews Dr. Byron Bailey, who shows slides of the oral and dental complications of spit tobacco use. The program describes how young players may be influenced by major league players, by advertising, and by peer pressure to use spit tobacco. Pitcher, Nolan Ryan, is interviewed about how he tries to influence young players not to use smokeless tobacco. Dr. Bailey discusses the addictive properties of nicotine, how spit tobacco hurts the teeth and gums, what to do if symptoms arise, diagnostic tests for oral cancer, and the importance of early diagnosis. Dr. Bailey also discusses surgical intervention often necessary to treat oral cancer, and shows postoperative slides of head and neck cancer patients. The program concludes with a section on how to quit using spit tobacco. After footage of another lively baseball game, the program ends with pictures of Sean Marsee, a young man who died of oral cancer related to smokeless tobacco use.
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Six Innings: The Little League Report Source: Columbia, MD: Romano and Associates, Inc. 199x. (videocassette). Contact: Available from National Spit Tobacco Education Program (NSTEP). Oral Health America, 410 North Michigan Avenue, Suite 352, Chicago, IL 60611-4211. (312) 836-9900. PRICE: $25.00. Summary: This program is designed to teach Little League baseball players about the hazards of spit (smokeless) tobacco (ST) use. Presented in the format of a news program, the video features two young people narrating like TV anchors. They first interview Joe Garagiola, who reviews the role and problem of tradition in baseball, why he got involved in the anti-ST program, why players use ST, and the importance of avoiding a habit that can become an addiction. The program reviews the association of ST with baseball, the dangers of ST, the percentage of children who use ST, the chemicals contained in ST, and the importance of never trying it. The program then features another youngster interviewing pro baseball player Joe Carter, who gives 4 reasons he has never tried ST: he's not easily influenced by other people, his wife wouldn't kiss him if he uses it, he knows of the cancer risks involved, and he thinks it's just like other drugs and can be addictive. He also briefly describes the difference between a bad habit and an addiction, noting the role of nicotine. The program also reviews a few moments from Little League history, focusing on 1964. The program ends with a repeat of the admonition not to try spit tobacco.
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Breaking the Chains: A Primary Care Team Smoking Cessation Intervention Strategy Source: Rosemont, PA, American Academy of Pediatrics, Pennsylvania Chapter, Clean Air for Healthy Children, 25-minute videotape, 2000. Contact: American Academy of Pediatrics, Pennsylvania Chapter, 919 Conestoga Road, Building 2, Suite 307, Rosemont, PA 19010. Summary: Breaking the Chains: A Primary Care Team Smoking Cessation Intervention Strategy is a 25-minute training video produced to increase smoking cessation counseling of parent and adolescent smokers by pediatricians and primary care providers. This video (1) educates primary care staff about the negative effects of smoking and passive smoke exposure, and (2) provides in-service training on smoking cessation techniques and strategies. The goal of this video is to encourage primary care staff to commit to implementing an office-based parent/patient focused smoking cessation program targeted at high risk families to break the chains of nicotine addiction. Besides primary care staff, other target audiences for this video are medical students and residents, and other health professionals seeking knowledge and skills to implement smoking cessation strategies with families in which either active or passive smoking has affected the health of family members. In this video, actors portray primary care staff during typical primary care office visits during which they illustrate interviewing and counseling techniques unique to their specific office responsibilities. After watching this video, viewers should be able to develop a smoking intervention plan tailored to their specific office environment that is based on the Smoking Cessation Guidelines for Clinicians by the Agency for Healthcare Research and Quality (AHRQ) that are demonstrated in this video. These guidelines are based on the counseling intervention known as STAGE that includes five steps: (1) Survey, (2) teachable moment, (3) assess, (4) give, and (5) evaluate. Accompanying this video is a fact sheet that provides (1) AHRQ recommendations and conclusions, (2) a description of the STAGE intervention, and (3) a description of the stages of behavior change and stage-dependent counseling tips.
Bibliography: Multimedia on Nicotine The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in nicotine (or synonyms). Then, in the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on nicotine: •
Animated neuroscience and the actions of nicotine, cocaine, and marijuana in the brain [videorecording] Source: a presentation of Films for the Humanities & Sciences; a Savantes production; Year: 1998; Format: Videorecording; Princeton, N.J.: Films for the Humanities & Sciences, c1998
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Drug abuse adv. cmte.-- smoking cessation products [videorecording]: Wellbutrin and nicotine inhaler. Year: 1996; Format: Videorecording; [United States: s.n., 1996?]
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Nicotine and caffeine [videorecording] Source: produced by the Office of Telecourses, Continuing Education, University of Washington and the School of Social Work, University of Washington, in cooperation with the Alcoholism and Drug Abuse Institute; Year: 1976; Format: Videorecording; [Seattle]: Roger A. Roffman, 1976
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The nicotine war [videorecording] Source: written, produced, and directed by Jon Palfreman; Year: 1994; Format: Videorecording; [Boston, Mass.]: WGBH Educational Foundation, c1994
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CHAPTER 9. PERIODICALS AND NEWS ON NICOTINE Overview In this chapter, we suggest a number of news sources and present various periodicals that cover nicotine.
News Services and Press Releases One of the simplest ways of tracking press releases on nicotine is to search the news wires. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing. PR Newswire To access the PR Newswire archive, simply go to http://www.prnewswire.com/. Select your country. Type “nicotine” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance. Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to nicotine. While some of the listed articles are free to view, others are available for purchase for a nominal fee. To access this archive, go to http://www.reutershealth.com/en/index.html and search by “nicotine” (or synonyms). The following was recently listed in this archive for nicotine: •
Long-term smoking abstinence with nicotine patches uncommon Source: Reuters Medical News Date: July 04, 2003 http://www.reutershealth.com/archive/2003/07/04/professional/links/20030704clin0 20.html
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Nicotine byproduct may counter Alzheimer's plaques Source: Reuters Health eLine Date: June 16, 2003
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Teens using, misusing nicotine replacement therapy Source: Reuters Health eLine Date: June 10, 2003
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Nicotine replacement products used and misused by adolescents Source: Reuters Medical News Date: June 10, 2003
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Nicotine-blocking drug may curb alcohol cravings Source: Reuters Health eLine Date: May 14, 2003
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Nicotine may speed lung cancer growth Source: Reuters Health eLine Date: March 26, 2003
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Nabi begins phase I/II European trial of nicotine vaccine Source: Reuters Industry Breifing Date: February 19, 2003
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Nicotine-free cigarettes available in 7 US states Source: Reuters Health eLine Date: January 27, 2003
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UK doctors call for nicotine watchdog Source: Reuters Health eLine Date: December 10, 2002
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British physicians to call for nicotine regulation Source: Reuters Health eLine Date: November 08, 2002
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Nicotine metabolite increases plasma levels of chemicals involved in aging Source: Reuters Medical News Date: October 31, 2002
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FDA okays OTC nicotine lozenge Source: Reuters Medical News Date: October 31, 2002
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Nicotine 'cooks' proteins in the body Source: Reuters Health eLine Date: October 28, 2002
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Brain scans shed light on nicotine's effects Source: Reuters Health eLine Date: October 23, 2002
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Mechanism by which nicotine contributes to SIDS risk explained in animal model Source: Reuters Medical News Date: September 11, 2002
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Nicotine replacement therapies seem to have lost efficacy with OTC status Source: Reuters Medical News Date: September 10, 2002
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Nicotine patches, gum less effective: study Source: Reuters Health eLine Date: September 10, 2002
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Mouse study gives clues to nicotine-SIDS link Source: Reuters Health eLine Date: September 09, 2002
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Tobacco company influenced nicotine gum, patch ads Source: Reuters Health eLine Date: August 14, 2002
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Fetal nicotine exposure tied to breathing problems Source: Reuters Health eLine Date: July 12, 2002
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US rules nicotine water is an unapproved drug Source: Reuters Health eLine Date: July 02, 2002
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FDA says nicotine water is unapproved drug Source: Reuters Industry Breifing Date: July 02, 2002
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Nicotine lozenges safe and effective for smoking cessation Source: Reuters Medical News Date: June 12, 2002
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Nabi begins human trial of nicotine vaccine Source: Reuters Industry Breifing Date: June 12, 2002
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Nicotine lozenges may help some smokers quit Source: Reuters Health eLine Date: June 11, 2002
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Nicotine suppresses antigrowth effects of retinoids in lung cancer cells Source: Reuters Medical News Date: May 14, 2002
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FDA: nicotine lollipops sold on web illegal Source: Reuters Health eLine Date: April 10, 2002
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Nicotine lollipops cause concern in US Source: Reuters Health eLine Date: April 03, 2002
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High nicotine levels found in lungs of SIDS cases Source: Reuters Medical News Date: March 28, 2002
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Endovasc plans to file IND for nicotine-based therapy shortly Source: Reuters Industry Breifing Date: February 06, 2002
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Nicotine damages arteries, ups heart disease risk Source: Reuters Health eLine Date: January 22, 2002
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Study: Pregnant women can use the nicotine patch Source: Reuters Health eLine Date: January 18, 2002
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Nicotine replacement seen as safe and effective in pregnancy Source: Reuters Industry Breifing Date: January 17, 2002
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Nicotine intake, metabolism may vary by ethnicity Source: Reuters Health eLine Date: January 15, 2002
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Nicotine poisoning traced to homemade skin cure Source: Reuters Health eLine Date: January 03, 2002
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Nicotine poisoning traced to homemade eczema treatment Source: Reuters Medical News Date: January 03, 2002 The NIH
Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “nicotine” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “nicotine” (or synonyms). If you know the name of a company that is relevant to nicotine, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/.
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BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “nicotine” (or synonyms).
Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “nicotine” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on nicotine: •
Head Noise: Annoying, But Rarely a Sign of a Serious Problem Source: Mayo Clinic Health Letter. 14(6): 4-5. June 1996. Contact: Available from Mayo Foundation for Medical Education and Research. 200 First Street, S.W., Rochester, MN 55905. (800) 633-4567. PRICE: $3.00 for single copy of newsletter plus shipping and handling. Summary: This newsletter article familiarizes readers with tinnitus, or head noises. Topics covered include the most common causes of tinnitus, including age-related hearing loss and noise-induced hearing loss; drug effects; other conditions that can amplify head noise; noise linked to blood flow; and treatment options including, avoiding irritants (such as loud noise, nicotine, and caffeine), masking the noise, using a hearing aid, and managing stress. The article encourages readers to seek ways to relieve their symptoms. 1 figure.
•
Smoking Cessation: More than Complication Prevention Source: Diabetes Care in Nova Scotia. 10(3): 1-2. July 2000. Contact: Available from Diabetes Care Program of Nova Scotia. P.O. Box 9000, 1278 Tower Road, Bethune Building, Suite 577, Halifax, Nova Scotia B3H 2Y9. (902) 473-3219. Fax (902) 473-3911. E-mail:
[email protected]. Summary: This article discusses the role of smoking in the development of type 2 diabetes. Although various studies have identified smoking as an independent risk factor for the development of type 2 diabetes, the mechanism by which cigarette smoking increases this risk is not clear. Substances in cigarette smoke may increase the levels of counterregulatory hormones to insulin, which may contribute to insulin resistance. In addition, nicotine impairs insulin action in the liver, adipose tissue, and muscle. Habitual smokers, especially those at risk for type 2 diabetes, should be advised to quit smoking or at least reduce the number of cigarettes smoked per day. However, health professionals cite various barriers to delivering cessation advice, including lack of time and payment for smoking cessation services, actual or perceived lack of knowledge and skill in cessation counseling, and low expectations regarding the efficacy of cessation counseling. The Agency for Health Care Policy and Research has identified the
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characteristics of successful smoking cessation interventions, including being delivered by a health care provider, offering either individual or group counseling, having greater person to person contact, providing aversive smoking techniques, being of long duration, and using pharmacotherapy. 5 references. •
Secrets of Successful Quitters Source: Diabetes Advisor. 7(5): 20-21. September-October 1999. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This article provides people who have diabetes with guidelines for quitting smoking. The article identifies the physical symptoms associated with quitting and explains that successful quitters go through several rounds of quitting and resuming smoking before they quit for good. The article presents initial steps that a person who wants to quit smoking needs to take and discusses the use of various nicotine replacement products to make withdrawal easier. Types of nicotine replacement products include the nicotine patch, nicotine gum, and nicotine nasal spray. In addition, the drug bupropion has been used as a smoking cessation aid since 1997. Other approaches to quitting include receiving formal training in the skills of quitting and undergoing acupuncture or hypnosis. The article also provides suggestions for reducing smoking as a way of easing into quitting and offers tips for making quitting easier, finding a smoking cessation program, and reducing postcessation weight gain.
•
Smoking Cessation: High Risk Groups (Part 3) Source: Druginform. 21(5):30-33, September-October 2000. Summary: This literature review considers the use of nicotine replacement and other smoking cessation strategies in groups of persons at increased risk of harmful effects resulting from smoking, including those with cardiovascular disease and pregnant and breastfeeding women. Compelling evidence exists that smoking causes between 17 to 30 percent of all deaths attributed to cardiovascular disease in the United States. The risk for coronary artery disease among smokers is dose related and smoking in the presence of other coronary risk factors such as hypertension and hypercholesterolemia has a synergistic effect on morbidity and mortality from coronary artery disease. Studies indicate nicotine patches are preferred to other forms of nicotine replacement therapy (NRT) with cardiovascular patients. Nasal sprays should be avoided due to higher blood levels produced. Uneventful NRT use has been documented 2 weeks after acute myocardial infarction, unstable angina, ventricular arrhythmia, and second-degree or higher AV block. Initial doses for the first 1 to 2 days should besmaller than usual. Smoking during pregnancy is associated with (1) intrauterine growth retardation, (2) increased risk o spontaneous abortion, (3) prematurity, (4) perinatal mortality, and (5) poor postnatal development. In addition to nicotine, the fetus may also be exposed to carbon monoxide and tar products. Currently, most NRT products are not licensed in the United Kingdom for use in pregnancy as safety data are lacking. Some suggest that the benefits of NRT outweigh the risk of smoking for pregnant women, but suggest this method be used only for women unable to stop any other way. Women who smoke during pregnancy are less likely to breast-feed and are more likely to wean their infants earlier. This effect appears to be dose related. Studies controlled for socioeconomic status have confirmed that smokers are more likely to fail at breast feeding than nonsmokers. Little information is available on the use of NRT in breast-feeding mothers, but levels of nicotine in breast milk are lower after NRT than after smoking. NRT
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products are devoid of tars, carbon monoxide, and respiratory irritants found in cigarettes. 28 references. •
Excerpts From the Placenta: To Know Me Is to Love Me. A Reference Guide for Gross Placental Examination: Maternal Indications for Placental Examination: Smoking Source: AAPA Quarterly Newsletter. Pp. 10-12, Winter 2000. Contact: INTERNET/EMAIL: http://www.pathologistassistants.org/Public_content/2001_NL_winner.pdf. Summary: The author describes the effects of smoking during pregnancy on the pregnancy, placenta, fetus, and neonate. Cigarette smoke contains over 300 toxic substances, including nicotine and carbon monoxide. Smoking reduces the ability of the woman to become pregnant in a dose dependent fashion. Women who smoke are at increased risk for first trimester spontaneous abortion. Maternal smoking causes a decrease in the fetal growth rate and causes a number of cardiorespiratory changes in the fetus, including increased heart rate, decreased fetal heart rate variability, clustered breathing movements, and that an increased chance a nonstress test will be positive. Smoking during pregnancy has been implicated to long-term deficits in mental development during infancy and behavioral problems, such as attention deficit disorder. The risk of meconium aspiration is also increased, along with a risk for mild-grade intracranial hemorrhage in the latter half of pregnancy in infants whose mothers smoked more than 10 cigarettes per day during the pregnancy. The placenta itself may show abruption, placenta extrachorialis, thin umbilical cord, velamentously inserted cord, single umbilical artery, chorioamnionitis, fetal stem vessel lesions, large infarcts, and changes associated with placenta previa due to smoking.
•
Helping Pregnant Women Kiss the Marlboro Man Goodbye: Smoking Cessation Guide for Clinicians and Educators Source: Reproductive Health Quarterly. 6:1-4, Winter 1999. Summary: Smoking by pregnant women relates to many health problems, such as pregnancy complications, low birthweight, and infant mortality. This article describes women who smoke, discussing elements of effective cessation and offering sources of further information for health professionals. Approximately 19 to 30 percent of pregnant women smoke and only 20 percent quit on their own while pregnant. Most women in this population resume smoking after birth. White women are more likely than African American and Hispanic women to smoke during pregnancy and to resume smoking after birth. Women with lower incomes and less education are most likely to smoke during pregnancy. Smoking is particularly dangerous for teen mothers because they are already at increased risk for adverse health outcomes. Research shows that women smoke because of such factors as weight control, depression, stress management, and nicotine addiction. Health care providers can be extremely influential in promoting smoking cessation. Suggestions for health care providers to help their pregnant clients quit include (1) establish how much and when the client smokes, (2) have the client set a quit date and develop a plan for tapering or quitting cold turkey, (3) use materials designed specifically for pregnant women and employ multiple teaching methods, (4) consider pharmacological aids under certain conditions, and (5) focus on relapse prevention after birth. 16 references.
•
How Not to Gain Weight When You Eat Low Fat Foods.Or When You Quit Smoking Source: University of California at Berkeley Wellness Letter. 13(7):5; April 1997.
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Contact: University of California at Berkeley Wellness Letter, P.O. Box 420148, Palm Coast, FL 32142. Summary: This pair of articles discusses the risk of weight gain in two different sets of circumstances. In the first, the authors review a study showing that women who think they are eating a low- fat snack will eat more at a subsequent meal than women who believe the snack is high-calorie. It comes down to the old truism that more calories must be expended than are consumed for weight loss to occur. The second part of the article focuses on weight after smoking cessation. According to the authors, no one is really sure why individuals who quit smoking tend to gain weight. One theory is that smoking raises the metabolic rate, so that more calories are burned. Another theory holds that the nicotine or other substances may curb appetite. A third opinion is that smokers eat to take the place of smoking. Whatever the reason, this article offers some tips to keep the weight gain to a minimum, including walking and eating raw vegetables when the urge for a cigarette strikes. The authors also caution against trying to quit smoking and lose weight at the same time, saying that individuals should try to quit smoking first since that is much more dangerous, and then lose weight. •
Thermogenesis and the Thermal Effect of Food Source: Healthy Weight Journal. 8(5):87-8, 98; September/October 1994. Contact: Healthy Living Institute, 402 S. 14th St., Hettinger, ND 58639. (701) 567-2645. Summary: This article focuses on thermogenesis, the energy expenditure due to food intake, cold exposure, thermogenic agents (such as caffeine and nicotine), and psychological influences. Most important is food's thermal effect of "diet-induced energy expenditure." Increasing attention is being paid to adaptive thermogenesis and its role in protecting weight by adjusting the balance the energy used with the energy or calories eaten. The author considers the thermal effect of food and the body's response to dietary fats. Individuals differ widely in their thermic response, leading researchers to believe that obese people may have a defective response.
Academic Periodicals covering Nicotine Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to nicotine. In addition to these sources, you can search for articles covering nicotine that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”
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APPENDICES
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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.
NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute12: •
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
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National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
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National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25
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National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm
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National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
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National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/
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These publications are typically written by one or more of the various NIH Institutes.
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National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm
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National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
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National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm
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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
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Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
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Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm
Physician Resources 523
NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.13 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:14 •
Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html
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HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
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NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html
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Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/
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Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html
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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
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Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html
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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
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MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html
13
Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 14 See http://www.nlm.nih.gov/databases/databases.html.
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Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html
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Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html The Combined Health Information Database
A comprehensive source of information on clinical guidelines written for professionals is the Combined Health Information Database. You will need to limit your search to one of the following: Brochure/Pamphlet, Fact Sheet, or Information Package, and “nicotine” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For the publication date, select “All Years.” Select your preferred language and the format option “Fact Sheet.” Type “nicotine” (or synonyms) into the “For these words:” box. The following is a sample result: •
Quitting Smoking: Nicotine Addiction in Minnesota Source: St. Paul, MN, Minnesota Partnership for Action Against Tobacco, 16 p., July 2001. Contact: Minnesota Partnership for Action Against Tobacco, 590 Park Street, Suite 400, St. Paul, MN 55103. (651) 224-0900. FAX: (651) 224-1700. INTERNET/EMAIL: http://www.health.state.mn.us/divs/chs/data/quittingsmoking.pdf;
[email protected]. Summary: Quitting Smoking: Nicotine Addiction in Minnesota provides data on Minnesotans' knowledge, attitudes, and behaviors concerning quitting smoking. Researchers conducted surveys of four groups of Minnesotans: (1) The general population of adults, (2) adult members of the Blue Plus MinnesotaCare Program, (3) adult members under age 65 years of the Blue Plus Prepaid Medical Assistance Program (PMAP), and (4) ninth to twelfth grade public school students. Smoking rates in the Blue Plus MinnesotaCare and Blue Plus PMAP were much higher than in the general population. These groups were in the lower income populations. They find quitting difficult because smoking is addictive. The level of a smoker's addiction to cigarettes affects the smoker's confidence in being able to quit. Issues that have motivated former smokers to quit include (1) information about the health hazards of tobacco, (2) a desire to be physically fit, (3) the smell and taste or appearance of smoking, (4) being a good example to children, (5) testing will power, (6) encouragement from a friend, (7) the cost of tobacco, (8) experiencing health problems linked to tobacco, (9) knowing a relative or a friend with tobacco-related illness, (10) advice from a physician, (11) restrictions on smoking at home, and (12) restrictions on smoking in the workplace. Barriers to quitting include cravings and feelings of withdrawal, loss of a way to handle stress, risk of gaining weight, cost of medications, cost of classes and other programs, and interference with social and work relationships. Quitting is especially difficult for teens who are frequent smokers.
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•
FTC Cigarette Test Method for Determining Tar, Nicotine, and Carbon Monoxide Yields of U.S. Cigarettes: Report of the NCI Expert Committee Source: Bethesda, MD, US Department of Health and Human Services, Public Health Service, National Institutes of Health, National Cancer Institute, Smoking and Tobacco Control Monograph 7, 275 p., August 1996. Contact: National Cancer Institute, Office of Cancer Communications, Building 31, Room 10A03, 31 Center Drive, MSC 2580, Bethesda, MD 20892-2580. (800) 422-6237. NIH Publication No. 96-4028. Summary: FTC Cigarette Test Method for Determining Tar, Nicotine, and Carbon Monoxide Yields of U.S. Cigarettes: Report of the NCI Expert Committee, the seventh in a series of Smoking and Tobacco monographs published by the National Cancer Institute (NCI) since 1991, presents the results of a consensus-style conference convened December 5-6, 1994. At the request of Congress, a scientific panel of experts was convened to review and make recommendations on the accuracy and appropriateness of the Federal Trade Commission's test method for assessing constituent yields for cigarettes on the U.S. market. The report consists of four main sections. Section one presents the 13 individual presentations of subject matter experts who made presentations to the NCI ad hoc committee. Issues discussed in these presentations included a historical overview of cigarette testing and the FTC; changes in cigarette design; attitudes, knowledge, and beliefs about low-yield cigarettes; cigarette smoke components and disease and changing disease risk; biomarkers of cigarette smoking; pharmacology and markers; consumer smoke perceptions of FTC tar ratings, and human smoking patterns. Section two presents a transcript of the Second Day's Discussion. Section three provides the Committee recommendations and findings, and Section four provides an Overview of 1980 and 1994 Research Related to the Standard Federal Trade Commission Test Method for Cigarettes.
The NLM Gateway15 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.16 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “nicotine” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category.
15 16
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH).
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Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total
Items Found 17592 206 106 15 27 17946
HSTAT17 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.18 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.19 Simply search by “nicotine” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
Coffee Break: Tutorials for Biologists20 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.21 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.22 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.
17
Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html.
18
The HSTAT URL is http://hstat.nlm.nih.gov/.
19
Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations. 20 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html. 21
The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 22 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.
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Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •
CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.
•
Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.
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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on nicotine can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.
Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to nicotine. Due to space limitations, these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly. The National Institutes of Health The NIH gateway to patients is located at http://health.nih.gov/. From this site, you can search across various sources and institutes, a number of which are summarized below. Topic Pages: MEDLINEplus The National Library of Medicine has created a vast and patient-oriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages” which list links to available materials relevant to nicotine. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas. Recently, MEDLINEplus listed the following when searched for “nicotine”:
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Other Guides Secondhand Smoke http://www.nlm.nih.gov/medlineplus/secondhandsmoke.html Smokeless Tobacco http://www.nlm.nih.gov/medlineplus/smokelesstobacco.html Smoking and Youth http://www.nlm.nih.gov/medlineplus/smokingandyouth.html
Within the health topic page dedicated to nicotine, the following was listed: •
General/Overviews Questions about Smoking, Tobacco, and Health Source: American Cancer Society http://www.cancer.org/docroot/PED/content/PED_10_2x_Questions_About_Sm oking_Tobacco_and_Health.asp Smoking Source: American Lung Association http://www.lungusa.org/tobacco/smoking_factsheet99.html Smoking - The Facts http://www.nlm.nih.gov/medlineplus/tutorials/smokingthefactsloader.html Some Truths about Tobacco Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=HQ01407
•
Specific Conditions/Aspects Cigar Smoking and Cancer Source: American Cancer Society http://www.cancer.org/docroot/ped/content/ped_10_2x_cigar_smoking_and_ca ncer.asp?sitearea=ped Cigarette Smoking: Tobacco-Related Diseases Kill Half of All Smokers Source: American Cancer Society http://www.cancer.org/docroot/ped/content/ped_10_2x_cigarette_smoking_and _cancer.asp?sitearea=ped Mind Over Matter - The Brain's Response to Nicotine Source: National Institute on Drug Abuse http://www.nida.nih.gov/MOM/NIC/MOMNIC1.html National Institute on Drug Abuse Research Report Series: Nicotine Addiction Source: National Institute on Drug Abuse http://www.nida.nih.gov/ResearchReports/Nicotine/Nicotine.html Questions and Answers about Cigar Smoking and Cancer Source: National Cancer Institute http://cis.nci.nih.gov/fact/3_65.htm
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Questions and Answers about Cigarette Smoking and Cancer Source: National Cancer Institute http://cis.nci.nih.gov/fact/3_14.htm Smoking and Elective Plastic Surgery - Some Surgeons Say “No” to Specific Procedures Source: American Society of Plastic Surgeons http://www.plasticsurgery.org/news_room/press_releases/Smoking-andElective-Plastic-Surgery.cfm Smoking and Musculoskeletal Health Source: American Academy of Orthopaedic Surgeons http://orthoinfo.aaos.org/fact/thr_report.cfm?Thread_ID=240&topcategory=Welln ess Smoking and the Workplace Source: American Lung Association http://www.lungusa.org/occupational/smoking_workplace.html Smoking and Your Digestive System Source: National Digestive Diseases Information Clearinghouse http://digestive.niddk.nih.gov/ddiseases/pubs/smoking/index.htm Smoking: How Does It Cause Wrinkles? Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=AN00644 Tobacco Products Source: American Dental Association http://www.ada.org/public/faq/tobacco.html Truth about “Light” Cigarettes: Questions and Answers Source: National Cancer Institute http://cis.nci.nih.gov/fact/3_74.htm •
From the National Institutes of Health Cigarettes and Other Nicotine Products Source: National Institute on Drug Abuse http://www.nida.nih.gov/infofax/tobacco.html
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Latest News Irish Minister Set on Smoke Ban After U.S. Trip Source: 09/19/2003, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_14038 .html More News on Smoking http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/alphanews_s.html#S moking New Study Shows State Tobacco Control Programs Cut Cigarette Sales Source: 09/18/2003, Centers for Disease Control and Prevention http://www.cdc.gov/od/oc/media/pressrel/r030918.htm
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PET Scans Show Cigarette Smoke Affects Peripheral Organs Source: 09/08/2003, National Institute on Drug Abuse http://www.nih.gov/news/pr/sep2003/nida-08.htm Smoking Killed Five Million Worldwide in 2000 Source: 09/12/2003, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_13976 .html Study Shows Smoking Effects Throughout Body Source: 09/09/2003, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_13927 .html •
Law and Policy State Legislated Actions on Tobacco Issues (SLATI) Source: American Lung Association http://slati.lungusa.org/
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Men Cigarettes Send Male Sex Life Up in Smoke Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=3009767 Prostate Cancer More Advanced in Men Who Smoke Source: American Cancer Society http://www.cancer.org/docroot/NWS/content/NWS_1_1x_Prostate_Cancer_Mor e_Advanced_in_Men_Who_Smoke.asp
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Organizations American Cancer Society http://www.cancer.org/ American Lung Association http://www.lungusa.org/ CDC's TIPS: Tobacco Information and Prevention Source Source: Centers for Disease Control and Prevention http://www.cdc.gov/tobacco/
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Pictures/Diagrams Images of Human Lungs Source: American Lung Association http://www.lungusa.org/learn/lung_images.html
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Prevention/Screening Check Your Smoking I.Q. Source: National Heart, Lung, and Blood Institute http://www.nhlbi.nih.gov/health/public/lung/other/smoking.html
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Research Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Trial Source: National Cancer Institute http://www.cancer.gov/newscenter/pressreleases/ATBCfollowup Associations between Smoking and Newer Risk Factors for Cardiovascular Disease Source: American College of Physicians http://www.annals.org/cgi/content/full/138/11/I-45 Cigarette Smoking among Adults--United States, 2000 Source: Centers for Disease Control and Prevention http://www.cdc.gov/tobacco/research_data/adults_prev/mmwr5129.pressrelease .htm New Study Shows State Tobacco Control Programs Cut Cigarette Sales Source: Centers for Disease Control and Prevention http://www.cdc.gov/od/oc/media/pressrel/r030918.htm Nicotine's Multiple Effects on the Brain's Reward System Drive Addiction Source: National Institute on Drug Abuse http://www.nida.nih.gov/NIDA_notes/NNVol17N6/Nicotine.html Persistent Smokers Skip Full Benefit of Angioplasty Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=3224 PET Scans Show Cigarette Smoke Affects Peripheral Organs Source: National Institute on Drug Abuse http://www.nih.gov/news/pr/sep2003/nida-08.htm Second National Report on Human Exposure to Environmental Chemicals: Cotinine Fact Sheet Source: National Center for Environmental Health http://www.cdc.gov/exposurereport/cotininefactsheet.htm Smoking Stokes Risk for Bleeding Strokes Source: American Stroke Association http://www.americanheart.org/presenter.jhtml?identifier=3010514 Vitamin C, Fish, and a Gout Drug Target Artery Damage from Smoking Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=3007365
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Statistics African Americans and Tobacco Source: Centers for Disease Control and Prevention http://www.cdc.gov/tobacco/sgr/sgr_1998/sgr-min-fs-afr.htm American Indians and Alaska Natives and Tobacco Source: Centers for Disease Control and Prevention http://www.cdc.gov/tobacco/sgr/sgr_1998/sgr-min-fs-nat.htm Asian Americans and Pacific Islanders and Tobacco Source: Centers for Disease Control and Prevention http://www.cdc.gov/tobacco/sgr/sgr_1998/sgr-min-fs-asi.htm
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Cigarette Smoking among Adults - United States, 2000 Source: Centers for Disease Control and Prevention http://www.cdc.gov/tobacco/research_data/adults_prev/mmwr5129_highlights. htm Cigarette Smoking-Related Mortality Source: Centers for Disease Control and Prevention http://www.cdc.gov/tobacco/research_data/health_consequences/mortali.htm Dangers of Cigarette Smoking Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=SK00002 Healthy People 2010: Tobacco Use Source: Centers for Disease Control and Prevention http://www.healthypeople.gov/document/html/volume2/27tobacco.htm Hispanics and Tobacco Source: Centers for Disease Control and Prevention http://www.cdc.gov/tobacco/sgr/sgr_1998/sgr-min-fs-hsp.htm National Tobacco Information Online System (NATIONS): Country Data Source: American Cancer Society, Centers for Disease Control and Prevention, World Health Organization http://apps.nccd.cdc.gov/nations/nations/country_specific_indicators.asp New AHRQ Data Indicate That People with Chronic Conditions Continue to Smoke Source: Agency for Healthcare Research and Quality http://www.ahrq.gov/news/press/pr2002/smokepr.htm Prevalence of Current Smoking among Adults Aged 18 Years and Over: United States, 1997 - 2002 Source: National Center for Health Statistics http://www.cdc.gov/nchs/about/major/nhis/released200212/figures08_18_4.htm Preventing Tobacco Use Source: National Center for Chronic Disease Prevention and Health Promotion http://www.cdc.gov/nccdphp/pe_factsheets/pe_tobacco.htm Tobacco Control: State Highlights 2002 Source: Centers for Disease Control and Prevention http://www.cdc.gov/tobacco/statehi/html_2002/state_highlights2002.htm •
Women Smokers at Higher Risk of Complications from Breast Reconstruction Surgery Source: American Cancer Society http://www.cancer.org/docroot/NWS/content/NWS_1_1x_Smokers_at_Higher_ Risk_of_Complications_from_Breast_Reconstruction_Surgery.asp Tobacco Use and Reproductive Outcomes - Fact Sheet Source: National Center for Chronic Disease Prevention and Health Promotion http://www.cdc.gov/tobacco/sgr/sgr_forwomen/factsheet_outcomes.htm
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Women and Smoking, a Report of the Surgeon General--2001: Summary Source: Centers for Disease Control and Prevention http://www.cdc.gov/tobacco/sgr/sgr_forwomen/ataglance.htm You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on nicotine. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •
What Do these Words Have in Common?: Gum Disease, Nicotine, Stained Teeth, Cancer, Bad Breath Source: Timonium, MD: American Lung Association of Maryland. 1993. 2 p. Contact: Available from American Lung Association of Maryland. 1840 York Road, Timonium, MD 21093. (800) 492-7527 (in Maryland) or (410) 560-2120. Also available from local American Lung Association chapters. PRICE: Single copy free. Stock Number 0606 8/93. Summary: This brochure, aimed at young adolescents, provides facts that encourage readers to avoid the use of smokeless tobacco. The brochure notes the different names used for smokeless tobacco and stresses that tobacco in any form is still tobacco, with the accompanying risks. Topics discussed include nicotine addiction, cancer, problems with bad breath, the impact of tobacco on the taste buds, and cost factors. The brochure includes a section of questions and answers on topics including: why some sports stars chew tobacco; the myth that smokeless tobacco is safer than smoking cigarettes; tobacco company ads; and legislation and warning labels on smokeless tobacco. The brochure concludes with a section of replies that young readers can use when someone offers them a chaw of tobacco. The brochure is illustrated with line drawings of young male adolescents and smokeless tobacco products. Healthfinder™
Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database:
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It's Quittin' Time: Smokers Need Not Rely on Willpower Alone Summary: This article discusses smoking cessation products, including the nicotine patch, that have been approved by the Food and Drug Administration (FDA) to help reduce the cravings and other withdrawal Source: U.S. Food and Drug Administration http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=3579
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Smoking Cessation/Tobacco Abuse - NetWellness Summary: This web site presents a general overview of the adverse effects of smoking, other tobacco abuses and nicotine addiction. Source: Nonprofit/Professional Entity--Follow the Resource URL for More Information http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=4879
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You Can Quit Smoking: A Consumer Guide Summary: This consumer version of the Clinical Practice Guideline No.18 addresses methods for quitting smoking and overcoming nicotine addiction. Source: Agency for Healthcare Research and Quality http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=5044 The NIH Search Utility
The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to nicotine. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources
A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/specific.htm
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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
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Med Help International: http://www.medhelp.org/HealthTopics/A.html
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Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
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Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
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WebMDHealth: http://my.webmd.com/health_topics
Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to nicotine. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with nicotine. The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about nicotine. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “nicotine” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “nicotine”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “nicotine” (or synonyms) into the “For these words:”
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box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “nicotine” (or a synonym) into the search box, and click “Submit Query.”
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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.
Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.23
Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.
Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of
23
Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.
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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)24: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
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Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
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Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
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California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html
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California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html
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California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html
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California: Gateway Health Library (Sutter Gould Medical Foundation)
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California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/
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California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
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California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
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California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/
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California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/
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California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/
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California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html
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California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/
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Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/
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Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/
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Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/
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Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
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Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml
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Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm
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Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
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Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
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Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
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Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
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Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
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Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
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Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
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Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
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Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
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Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
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Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
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Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
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Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
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Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm
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Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
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Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
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Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10
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Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/
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Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html
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Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
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Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp
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Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
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Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html
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Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
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Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp
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Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/
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Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html
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Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/
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Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
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Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
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Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
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Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm
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Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330
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Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
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National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
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National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/
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National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
Finding Medical Libraries 543
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Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm
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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
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New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm
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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm
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New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/
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New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
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New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/
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New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html
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New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/
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Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm
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Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp
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Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/
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Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/
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Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml
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Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html
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Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html
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Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml
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Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp
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Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm
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Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/
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South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp
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Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/
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Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/
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Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72
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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •
ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html
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MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
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Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
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Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html
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On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/
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Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp
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Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm
Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on nicotine: •
Basic Guidelines for Nicotine Nicotine overdose Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002510.htm Nicotine withdrawal Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000953.htm
•
Signs & Symptoms for Nicotine Abdominal cramps Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003120.htm Agitation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003212.htm Collapse Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003092.htm
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Coma Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003202.htm Confusion Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003205.htm Convulsions Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003200.htm Depression Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003213.htm Difficulty breathing Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003075.htm Drooling Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003048.htm Emesis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm Excitement Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003212.htm Headache Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003024.htm Increased salivation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003048.htm Mouth lesions Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003059.htm No breathing Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003069.htm Pounding heartbeat Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003081.htm Rapid breathing Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003071.htm Restlessness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003212.htm Vomitting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm Weakness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003174.htm
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•
Diagnostics and Tests for Nicotine Blood pressure Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003398.htm Gastric lavage Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003882.htm Heart rate Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003399.htm Muscular twitching Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003924.htm
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Background Topics for Nicotine Respiratory Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002290.htm Smoking - tips on how to quit Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001992.htm Smoking hazards Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001994.htm
Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •
Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical
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MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html
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Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
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Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
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NICOTINE DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Abortion: 1. The premature expulsion from the uterus of the products of conception - of the embryo, or of a nonviable fetus. The four classic symptoms, usually present in each type of abortion, are uterine contractions, uterine haemorrhage, softening and dilatation of the cervix, and presentation or expulsion of all or part of the products of conception. 2. Premature stoppage of a natural or a pathological process. [EU] Abscess: Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. [NIH] Absenteeism: Chronic absence from work or other duty. [NIH] Acantholysis: Separation of the prickle cells of the stratum spinosum of the epidermis, resulting in atrophy of the prickle cell layer. It is seen in diseases such as pemphigus vulgaris (see pemphigus) and keratosis follicularis. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acculturation: Process of cultural change in which one group or members of a group assimilates various cultural patterns from another. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acidity: The quality of being acid or sour; containing acid (hydrogen ions). [EU] Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Acoustic: Having to do with sound or hearing. [NIH] Acquired Immunodeficiency Syndrome: An acquired defect of cellular immunity associated with infection by the human immunodeficiency virus (HIV), a CD4-positive Tlymphocyte count under 200 cells/microliter or less than 14% of total lymphocytes, and increased susceptibility to opportunistic infections and malignant neoplasms. Clinical manifestations also include emaciation (wasting) and dementia. These elements reflect criteria for AIDS as defined by the CDC in 1993. [NIH] Acrylonitrile: A highly poisonous compound used widely in the manufacture of plastics, adhesives and synthetic rubber. [NIH] Actin: Essential component of the cell skeleton. [NIH] Acuity: Clarity or clearness, especially of the vision. [EU]
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Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adduct: Complex formed when a carcinogen combines with DNA or a protein. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of cyclic AMP and pyrophosphate from ATP. EC 4.6.1.1. [NIH] Adhesives: Substances that cause the adherence of two surfaces. They include glues (properly collagen-derived adhesives), mucilages, sticky pastes, gums, resins, or latex. [NIH] Adipocytes: Fat-storing cells found mostly in the abdominal cavity and subcutaneous tissue. Fat is usually stored in the form of tryglycerides. [NIH] Adipose Tissue: Connective tissue composed of fat cells lodged in the meshes of areolar tissue. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Glands: Paired glands situated in the retroperitoneal tissues at the superior pole of each kidney. [NIH] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adrenolytic: Inhibiting the action of adrenergic nerves; inhibiting the response to epinephrine. [EU] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]
Aetiology: Study of the causes of disease. [EU] Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the
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complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [NIH] Ageing: A physiological or morphological change in the life of an organism or its parts, generally irreversible and typically associated with a decline in growth and reproductive vigor. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Agoraphobia: Obsessive, persistent, intense fear of open places. [NIH] Air Sacs: Thin-walled sacs or spaces which function as a part of the respiratory system in birds, fishes, insects, and mammals. [NIH] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Akathisia: 1. A condition of motor restlessness in which there is a feeling of muscular quivering, an urge to move about constantly, and an inability to sit still, a common extrapyramidal side effect of neuroleptic drugs. 2. An inability to sit down because of intense anxiety at the thought of doing so. [EU] Aldehydes: Organic compounds containing a carbonyl group in the form -CHO. [NIH] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alkaline: Having the reactions of an alkali. [EU] Alkaline Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.1. [NIH] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Alloys: A mixture of metallic elements or compounds with other metallic or metalloid elements in varying proportions. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH]
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Alternative Splicing: A process whereby multiple protein isoforms are generated from a single gene. Alternative splicing involves the splicing together of nonconsecutive exons during the processing of some, but not all, transcripts of the gene. Thus a particular exon may be connected to any one of several alternative exons to form messenger RNA. The alternative forms produce proteins in which one part is common while the other part is different. [NIH] Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98. [NIH] Alveoli: Tiny air sacs at the end of the bronchioles in the lungs. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Alcohols: Compounds possessing both a hydroxyl (-OH) and an amino group (NH2). [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amnion: The extraembryonic membrane which contains the embryo and amniotic fluid. [NIH]
Amniotic Fluid: Amniotic cavity fluid which is produced by the amnion and fetal lungs and kidneys. [NIH] Amphetamine: A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is dextroamphetamine. [NIH] Amygdala: Almond-shaped group of basal nuclei anterior to the inferior horn of the lateral ventricle of the brain, within the temporal lobe. The amygdala is part of the limbic system. [NIH]
Amyloid: A general term for a variety of different proteins that accumulate as extracellular fibrils of 7-10 nm and have common structural features, including a beta-pleated sheet conformation and the ability to bind such dyes as Congo red and thioflavine (Kandel, Schwartz, and Jessel, Principles of Neural Science, 3rd ed). [NIH] Amyloid beta-Protein: A 4 kD protein, 39-43 amino acids long, expressed by a gene located
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on chromosome 21. It is the major protein subunit of the vascular and plaque amyloid filaments in individuals with Alzheimer's disease and in aged individuals with trisomy 21 (Down syndrome). The protein is found predominantly in the nervous system, but there have been reports of its presence in non-neural tissue. [NIH] Amyloidosis: A group of diseases in which protein is deposited in specific organs (localized amyloidosis) or throughout the body (systemic amyloidosis). Amyloidosis may be either primary (with no known cause) or secondary (caused by another disease, including some types of cancer). Generally, primary amyloidosis affects the nerves, skin, tongue, joints, heart, and liver; secondary amyloidosis often affects the spleen, kidneys, liver, and adrenal glands. [NIH] Anabasine: A botanical insecticide. [NIH] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analeptic: A drug which acts as a restorative, such as caffeine, amphetamine, pentylenetetrazol, etc. [EU] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anergy: Absence of immune response to particular substances. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Angina: Chest pain that originates in the heart. [NIH] Anginal: Pertaining to or characteristic of angina. [EU] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Anhydrous: Deprived or destitute of water. [EU] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Anomalies: Birth defects; abnormalities. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms.
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[NIH]
Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticholinergic: An agent that blocks the parasympathetic nerves. Called also parasympatholytic. [EU] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antidepressant: A drug used to treat depression. [NIH] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [EU]
Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-presenting cell: APC. A cell that shows antigen on its surface to other cells of the immune system. This is an important part of an immune response. [NIH] Antihistamine: A drug that counteracts the action of histamine. The antihistamines are of two types. The conventional ones, as those used in allergies, block the H1 histamine receptors, whereas the others block the H2 receptors. Called also antihistaminic. [EU] Antihypertensive: An agent that reduces high blood pressure. [EU] Anti-infective: An agent that so acts. [EU] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antipruritic: Relieving or preventing itching. [EU] Antipsychotic: Effective in the treatment of psychosis. Antipsychotic drugs (called also neuroleptic drugs and major tranquilizers) are a chemically diverse (including phenothiazines, thioxanthenes, butyrophenones, dibenzoxazepines, dibenzodiazepines, and diphenylbutylpiperidines) but pharmacologically similar class of drugs used to treat schizophrenic, paranoid, schizoaffective, and other psychotic disorders; acute delirium and dementia, and manic episodes (during induction of lithium therapy); to control the movement disorders associated with Huntington's chorea, Gilles de la Tourette's syndrome, and ballismus; and to treat intractable hiccups and severe nausea and vomiting. Antipsychotic agents bind to dopamine, histamine, muscarinic cholinergic, a-adrenergic, and serotonin receptors. Blockade of dopaminergic transmission in various areas is thought
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to be responsible for their major effects : antipsychotic action by blockade in the mesolimbic and mesocortical areas; extrapyramidal side effects (dystonia, akathisia, parkinsonism, and tardive dyskinesia) by blockade in the basal ganglia; and antiemetic effects by blockade in the chemoreceptor trigger zone of the medulla. Sedation and autonomic side effects (orthostatic hypotension, blurred vision, dry mouth, nasal congestion and constipation) are caused by blockade of histamine, cholinergic, and adrenergic receptors. [EU] Antispasmodic: An agent that relieves spasm. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Anxiolytic: An anxiolytic or antianxiety agent. [EU] Aorta: The main trunk of the systemic arteries. [NIH] Aortic Aneurysm: Aneurysm of the aorta. [NIH] Apathy: Lack of feeling or emotion; indifference. [EU] Aperture: A natural hole of perforation, especially one in a bone. [NIH] Apolipoproteins: The protein components of lipoproteins which remain after the lipids to which the proteins are bound have been removed. They play an important role in lipid transport and metabolism. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Appetitive Behavior: Animal searching behavior. The variable introductory phase of an instinctive behavior pattern or sequence, e.g., looking for food, or sequential courtship patterns prior to mating. [NIH] Approximate: Approximal [EU] Aqueous: Having to do with water. [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arecoline: An alkaloid obtained from the betel nut (Areca catechu), fruit of a palm tree. It is an agonist at both muscarinic and nicotinic acetycholine receptors. It is used in the form of various salts as a ganglionic stimulant, a parasympathomimetic, and a vermifuge, especially in veterinary practice. It has been used as a euphoriant in the Pacific Islands. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatic: Having a spicy odour. [EU] Arrhythmia: Any variation from the normal rhythm or rate of the heart beat. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH]
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Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Ascorbic Acid: A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant. [NIH] Aseptic: Free from infection or septic material; sterile. [EU] Aspartic: The naturally occurring substance is L-aspartic acid. One of the acidic-amino-acids is obtained by the hydrolysis of proteins. [NIH] Aspartic Acid: One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter. [NIH] Asphyxia: A pathological condition caused by lack of oxygen, manifested in impending or actual cessation of life. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astringents: Agents, usually topical, that cause the contraction of tissues for the control of bleeding or secretions. [NIH] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Astrocytoma: A tumor that begins in the brain or spinal cord in small, star-shaped cells called astrocytes. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Atracurium: A non-depolarizing neuromuscular blocking agent with short duration of action. Its lack of significant cardiovascular effects and its lack of dependence on good kidney function for elimination provide clinical advantage over alternate non-depolarizing neuromuscular blocking agents. [NIH] Atrial: Pertaining to an atrium. [EU] Atrial Fibrillation: Disorder of cardiac rhythm characterized by rapid, irregular atrial impulses and ineffective atrial contractions. [NIH] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Atropine: A toxic alkaloid, originally from Atropa belladonna, but found in other plants, mainly Solanaceae. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to
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strains of unusual type. [EU] Auditory: Pertaining to the sense of hearing. [EU] Autodigestion: Autolysis; a condition found in disease of the stomach: the stomach wall is digested by the gastric juice. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the central nervous system, especially the hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [NIH] Autoradiography: A process in which radioactive material within an object produces an image when it is in close proximity to a radiation sensitive emulsion. [NIH] Aversion therapy: Negative conditioning, consisting of pairing the unwanted symptom or behavior (e. g. alcoholism) with painful or unpleasant stimuli until the undesirable behavior is suppressed. [NIH] Avian: A plasmodial infection in birds. [NIH] Axonal: Condition associated with metabolic derangement of the entire neuron and is manifest by degeneration of the distal portion of the nerve fiber. [NIH] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial toxin: A toxic substance, made by bacteria, that can be modified to kill specific tumor cells without harming normal cells. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Basal cells: Small, round cells found in the lower part (or base) of the epidermis, the outer layer of the skin. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Behavior Therapy: The application of modern theories of learning and conditioning in the treatment of behavior disorders. [NIH] Belladonna: A species of very poisonous Solanaceous plants yielding atropine
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(hyoscyamine), scopolamine, and other belladonna alkaloids, used to block the muscarinic autonomic nervous system. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]
Bentonite: A colloidal, hydrated aluminum silicate that swells 12 times its dry size when added to water. [NIH] Benzene: Toxic, volatile, flammable liquid hydrocarbon biproduct of coal distillation. It is used as an industrial solvent in paints, varnishes, lacquer thinners, gasoline, etc. Benzene causes central nervous system damage acutely and bone marrow damage chronically and is carcinogenic. It was formerly used as parasiticide. [NIH] Benzodiazepines: A two-ring heterocyclic compound consisting of a benzene ring fused to a diazepine ring. Permitted is any degree of hydrogenation, any substituents and any Hisomer. [NIH] Beta-Endorphin: A peptide consisting of amino acid sequence 61-91 of the endogenous pituitary hormone beta-lipotropin. The first four amino acids show a common tetrapeptide sequence with methionine- and leucine enkephalin. The compound shows opiate-like activity. Injection of beta-endorphin induces a profound analgesia of the whole body for several hours. This action is reversed after administration of naloxone. [NIH] Beta-pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile duct: A tube through which bile passes in and out of the liver. [NIH] Bile Pigments: Pigments that give a characteristic color to bile including: bilirubin, biliverdine, and bilicyanin. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Biliary Tract: The gallbladder and its ducts. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biochemical reactions: In living cells, chemical reactions that help sustain life and allow cells to grow. [NIH] Biogenic Amines: A group of naturally occurring amines derived by enzymatic decarboxylation of the natural amino acids. Many have powerful physiological effects (e.g., histamine, serotonin, epinephrine, tyramine). Those derived from aromatic amino acids, and also their synthetic analogs (e.g., amphetamine), are of use in pharmacology. [NIH] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived
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constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [NIH] Biphasic: Having two phases; having both a sporophytic and a gametophytic phase in the life cycle. [EU] Bipolar Disorder: A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence. [NIH] Birth Certificates: Official certifications by a physician recording the individual's birth date, place of birth, parentage and other required identifying data which are filed with the local registrar of vital statistics. [NIH] Bladder: The organ that stores urine. [NIH] Blastocyst: The mammalian embryo in the post-morula stage in which a fluid-filled cavity, enclosed primarily by trophoblast, contains an inner cell mass which becomes the embryonic disc. [NIH] Blepharospasm: Excessive winking; tonic or clonic spasm of the orbicularis oculi muscle. [NIH]
Blinking: Brief closing of the eyelids by involuntary normal periodic closing, as a protective measure, or by voluntary action. [NIH] Blister: Visible accumulations of fluid within or beneath the epidermis. [NIH] Blood Cell Count: A count of the number of leukocytes and erythrocytes per unit volume in a sample of venous blood. A complete blood count (CBC) also includes measurement of the hemoglobin, hematocrit, and erythrocyte indices. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood-Brain Barrier: Specialized non-fenestrated tightly-joined endothelial cells (tight junctions) that form a transport barrier for certain substances between the cerebral capillaries and the brain tissue. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Body Mass Index: One of the anthropometric measures of body mass; it has the highest
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correlation with skinfold thickness or body density. [NIH] Body Regions: Anatomical areas of the body. [NIH] Bombesin: A tetradecapeptide originally obtained from the skins of toads Bombina bombina and B. variegata. It is also an endogenous neurotransmitter in many animals including mammals. Bombesin affects vascular and other smooth muscle, gastric secretion, and renal circulation and function. [NIH] Bone Cements: Adhesives used to fix prosthetic devices to bones and to cement bone to bone in difficult fractures. Synthetic resins are commonly used as cements. A mixture of monocalcium phosphate, monohydrate, alpha-tricalcium phosphate, and calcium carbonate with a sodium phosphate solution is also a useful bone paste. [NIH] Bone Density: The amount of mineral per square centimeter of bone. This is the definition used in clinical practice. Actual bone density would be expressed in grams per milliliter. It is most frequently measured by photon absorptiometry or x-ray computed tomography. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Boron: A trace element with the atomic symbol B, atomic number 5, and atomic weight 10.81. Boron-10, an isotope of boron, is used as a neutron absorber in boron neutron capture therapy. [NIH] Boron Neutron Capture Therapy: A technique for the treatment of neoplasms, especially gliomas and melanomas in which boron-10, an isotope, is introduced into the target cells followed by irradiation with thermal neutrons. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Bradykinesia: Abnormal slowness of movement; sluggishness of physical and mental responses. [EU] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]
Breakdown: A physical, metal, or nervous collapse. [NIH] Bromine: A halogen with the atomic symbol Br, atomic number 36, and atomic weight 79.904. It is a volatile reddish-brown liquid that gives off suffocating vapors, is corrosive to the skin, and may cause severe gastroenteritis if ingested. [NIH]
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Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchioles: The tiny branches of air tubes in the lungs. [NIH] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Buccal mucosa: The inner lining of the cheeks and lips. [NIH] Bupropion: A unicyclic, aminoketone antidepressant. The mechanism of its therapeutic actions is not well understood, but it does appear to block dopamine uptake. The hydrochloride is available as an aid to smoking cessation treatment. [NIH] Buspirone: An anxiolytic agent and a serotonin receptor agonist belonging to the azaspirodecanedione class of compounds. Its structure is unrelated to those of the benzodiazepines, but it has an efficacy comparable to diazepam. [NIH] Cacao: A tree of the family Sterculiaceae (or Byttneriaceae), usually Theobroma cacao, or its seeds, which after fermentation and roasting, yield cocoa and chocolate. [NIH] Cadmium: An element with atomic symbol Cd, atomic number 48, and atomic weight 114. It is a metal and ingestion will lead to cadmium poisoning. [NIH] Cadmium Poisoning: Poisoning occurring after exposure to cadmium compounds or fumes. It may cause gastrointestinal syndromes, anemia, or pneumonitis. [NIH] Caesarean section: A surgical incision through the abdominal and uterine walls in order to deliver a baby. [NIH] Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium Carbonate: Carbonic acid calcium salt (CaCO3). An odorless, tasteless powder or crystal that occurs in nature. It is used therapeutically as a phosphate buffer in hemodialysis patients and as a calcium supplement. [NIH] Cannabis: The hemp plant Cannabis sativa. Products prepared from the dried flowering tops of the plant include marijuana, hashish, bhang, and ganja. [NIH] Capsaicin: Cytotoxic alkaloid from various species of Capsicum (pepper, paprika), of the Solanaceae. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen
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are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]
Cardiac: Having to do with the heart. [NIH] Cardiac arrest: A sudden stop of heart function. [NIH] Cardiorespiratory: Relating to the heart and lungs and their function. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Cardiovascular System: The heart and the blood vessels by which blood is pumped and circulated through the body. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Catheter: A flexible tube used to deliver fluids into or withdraw fluids from the body. [NIH] Cathode: An electrode, usually an incandescent filament of tungsten, which emits electrons in an X-ray tube. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Caudate Nucleus: Elongated gray mass of the neostriatum located adjacent to the lateral ventricle of the brain. [NIH] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral
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proteins are embedded to varying degrees. [EU] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cellobiose: A disaccharide consisting of two glucose units in beta (1-4) glycosidic linkage. Obtained from the partial hydrolysis of cellulose. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Centrifugation: A method of separating organelles or large molecules that relies upon differential sedimentation through a preformed density gradient under the influence of a gravitational field generated in a centrifuge. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Cortex: The thin layer of gray matter on the surface of the cerebral hemisphere that develops from the telencephalon and folds into gyri. It reaches its highest development in man and is responsible for intellectual faculties and higher mental functions. [NIH] Cerebral hemispheres: The two halves of the cerebrum, the part of the brain that controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. The right hemisphere controls muscle movement on the left side of the body, and the left hemisphere controls muscle movement on the right side of the body. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Cetirizine: A potent second-generation histamine H1 antagonist that is effective in the treatment of allergic rhinitis, chronic urticaria, and pollen-induced asthma. Unlike many traditional antihistamines, it does not cause drowsiness or anticholinergic side effects. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chemoreceptor: A receptor adapted for excitation by chemical substances, e.g., olfactory and gustatory receptors, or a sense organ, as the carotid body or the aortic (supracardial) bodies, which is sensitive to chemical changes in the blood stream, especially reduced
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oxygen content, and reflexly increases both respiration and blood pressure. [EU] Chimeras: Organism that contains a mixture of genetically different cells. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] Chlordiazepoxide: An anxiolytic benzodiazepine derivative with anticonvulsant, sedative, and amnesic properties. It has also been used in the symptomatic treatment of alcohol withdrawl. [NIH] Chlorine: A greenish-yellow, diatomic gas that is a member of the halogen family of elements. It has the atomic symbol Cl, atomic number 17, and atomic weight 70.906. It is a powerful irritant that can cause fatal pulmonary edema. Chlorine is used in manufacturing, as a reagent in synthetic chemistry, for water purification, and in the production of chlorinated lime, which is used in fabric bleaching. [NIH] Chlorophyll: Porphyrin derivatives containing magnesium that act to convert light energy in photosynthetic organisms. [NIH] Chlorpromazine: The prototypical phenothiazine antipsychotic drug. Like the other drugs in this class chlorpromazine's antipsychotic actions are thought to be due to long-term adaptation by the brain to blocking dopamine receptors. Chlorpromazine has several other actions and therapeutic uses, including as an antiemetic and in the treatment of intractable hiccup. [NIH] Chlorpyrifos: An organothiophosphate cholinesterase inhibitor that is used as an insecticide and as an acaricide. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis. [NIH] Choline: A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Cholinergic Agonists: Drugs that bind to and activate cholinergic receptors. [NIH] Cholinesterase Inhibitors: Drugs that inhibit cholinesterases. The neurotransmitter acetylcholine is rapidly hydrolyzed, and thereby inactivated, by cholinesterases. When cholinesterases are inhibited, the action of endogenously released acetylcholine at cholinergic synapses is potentiated. Cholinesterase inhibitors are widely used clinically for their potentiation of cholinergic inputs to the gastrointestinal tract and urinary bladder, the eye, and skeletal muscles; they are also used for their effects on the heart and the central nervous system. [NIH] Chondrocytes: Polymorphic cells that form cartilage. [NIH] Chorda Tympani Nerve: A branch of the facial (7th cranial) nerve which passes through the middle ear and continues through the petrotympanic fissure. The chorda tympani nerve carries taste sensation from the anterior two-thirds of the tongue and conveys parasympathetic efferents to the salivary glands. [NIH]
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Chorea: Involuntary, forcible, rapid, jerky movements that may be subtle or become confluent, markedly altering normal patterns of movement. Hypotonia and pendular reflexes are often associated. Conditions which feature recurrent or persistent episodes of chorea as a primary manifestation of disease are referred to as choreatic disorders. Chorea is also a frequent manifestation of basal ganglia diseases. [NIH] Chorioamnionitis: An inflammatory process involving the chorion, its fetal blood vessels, the umbilical cord, and the amnion by extension of the inflammation, as the amnion itself has no blood supply. This inflammatory process is potentially fatal to mother and fetus. [NIH]
Chorion: The outermost extraembryonic membrane. [NIH] Chromaffin Cells: Cells that store epinephrine secretory vesicles. During times of stress, the nervous system signals the vesicles to secrete their hormonal content. Their name derives from their ability to stain a brownish color with chromic salts. Characteristically, they are located in the adrenal medulla and paraganglia (paraganglia, chromaffin) of the sympathetic nervous system. [NIH] Chromans: Benzopyrans saturated in the 2 and 3 positions. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromic: Catgut sterilized and impregnated with chromium trioxide. [NIH] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic Obstructive Pulmonary Disease: Collective term for chronic bronchitis and emphysema. [NIH] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [NIH] Circadian: Repeated more or less daily, i. e. on a 23- to 25-hour cycle. [NIH] Circulatory system: The system that contains the heart and the blood vessels and moves blood throughout the body. This system helps tissues get enough oxygen and nutrients, and it helps them get rid of waste products. The lymph system, which connects with the blood system, is often considered part of the circulatory system. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Cisplatin: An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. [NIH] Citric Acid: A key intermediate in metabolism. It is an acid compound found in citrus fruits. The salts of citric acid (citrates) can be used as anticoagulants due to their calcium chelating ability. [NIH] Citrus: Any tree or shrub of the Rue family or the fruit of these plants. [NIH] Clear cell carcinoma: A rare type of tumor of the female genital tract in which the inside of the cells looks clear when viewed under a microscope. [NIH]
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Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]
Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clonazepam: An anticonvulsant used for several types of seizures, including myotonic or atonic seizures, photosensitive epilepsy, and absence seizures, although tolerance may develop. It is seldom effective in generalized tonic-clonic or partial seizures. The mechanism of action appears to involve the enhancement of gaba receptor responses. [NIH] Clonic: Pertaining to or of the nature of clonus. [EU] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Cobalt: A trace element that is a component of vitamin B12. It has the atomic symbol Co, atomic number 27, and atomic weight 58.93. It is used in nuclear weapons, alloys, and pigments. Deficiency in animals leads to anemia; its excess in humans can lead to erythrocytosis. [NIH] Coca: Any of several South American shrubs of the Erythroxylon genus (and family) that yield cocaine; the leaves are chewed with alum for CNS stimulation. [NIH] Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. [NIH] Cochlear: Of or pertaining to the cochlea. [EU] Cochlear Diseases: Diseases of the cochlea, the part of the inner ear that is concerned with hearing. [NIH] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] Cognitive restructuring: A method of identifying and replacing fear-promoting, irrational beliefs with more realistic and functional ones. [NIH] Colchicine: A major alkaloid from Colchicum autumnale L. and found also in other Colchicum species. Its primary therapeutic use is in the treatment of gout, but it has been used also in the therapy of familial Mediterranean fever (periodic disease). [NIH] Colic: Paroxysms of pain. This condition usually occurs in the abdominal region but may occur in other body regions as well. [NIH] Colitis: Inflammation of the colon. [NIH]
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Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Colloidal: Of the nature of a colloid. [EU] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] Comorbidity: The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such
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as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] Compliance: Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. [NIH] Compulsions: In psychology, an irresistible urge, sometimes amounting to obsession to perform a particular act which usually is carried out against the performer's will or better judgment. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Confounding: Extraneous variables resulting in outcome effects that obscure or exaggerate the "true" effect of an intervention. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective
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tissue cells embedded in a large amount of extracellular matrix. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Contact dermatitis: Inflammation of the skin with varying degrees of erythema, edema and vesinculation resulting from cutaneous contact with a foreign substance or other exposure. [NIH]
Continuous infusion: The administration of a fluid into a blood vessel, usually over a prolonged period of time. [NIH] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]
Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Corneum: The superficial layer of the epidermis containing keratinized cells. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Arteriosclerosis: Thickening and loss of elasticity of the coronary arteries. [NIH] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corpus: The body of the uterus. [NIH] Corpus Luteum: The yellow glandular mass formed in the ovary by an ovarian follicle that has ruptured and discharged its ovum. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Corticosteroids: Hormones that have antitumor activity in lymphomas and lymphoid leukemias; in addition, corticosteroids (steroids) may be used for hormone replacement and for the management of some of the complications of cancer and its treatment. [NIH] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cotinine: 1-Methyl-5-(3-pyridyl)-2-pyrrolidinone antidepressant. Synonym: Scotine. [NIH]
fumarate.
Stimulant
proposed
as
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Coumarin: A fluorescent dye. [NIH] Courtship: The mutual attraction between individuals of the opposite sex. [NIH] Crack Cocaine: The purified, alkaloidal, extra-potent form of cocaine. It is smoked (freebased), injected intravenously, and orally ingested. Use of crack results in alterations in function of the cardiovascular system, the autonomic nervous system, the central nervous system, and the gastrointestinal system. The slang term "crack" was derived from the crackling sound made upon igniting of this form of cocaine for smoking. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Cruciferous vegetables: A family of vegetables that includes kale, collard greens, broccoli, cauliflower, cabbage, brussels sprouts, and turnip. These vegetables contain substances that may protect against cancer. [NIH] Cues: Signals for an action; that specific portion of a perceptual field or pattern of stimuli to which a subject has learned to respond. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyanide: An extremely toxic class of compounds that can be lethal on inhaling of ingesting in minute quantities. [NIH] Cyanogen Bromide: Cyanogen bromide (CNBr). A compound used in molecular biology to digest some proteins and as a coupling reagent for phosphoroamidate or pyrophosphate internucleotide bonds in DNA duplexes. [NIH] Cyanosis: A bluish or purplish discoloration of the skin and mucous membranes due to an increase in the amount of deoxygenated hemoglobin in the blood or a structural defect in the hemoglobin molecule. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU]
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Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] Cytotoxic chemotherapy: Anticancer drugs that kill cells, especially cancer cells. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] De novo: In cancer, the first occurrence of cancer in the body. [NIH] Deamination: The removal of an amino group (NH2) from a chemical compound. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Decidua: The epithelial lining of the endometrium that is formed before the fertilized ovum reaches the uterus. The fertilized ovum embeds in the decidua. If the ovum is not fertilized, the decidua is shed during menstruation. [NIH] Decision Making: The process of making a selective intellectual judgment when presented with several complex alternatives consisting of several variables, and usually defining a course of action or an idea. [NIH] Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delirium: (DSM III-R) an acute, reversible organic mental disorder characterized by reduced ability to maintain attention to external stimuli and disorganized thinking as manifested by rambling, irrelevant, or incoherent speech; there are also a reduced level of consciousness, sensory misperceptions, disturbance of the sleep-wakefulness cycle and level of psychomotor activity, disorientation to time, place, or person, and memory impairment. Delirium may be caused by a large number of conditions resulting in derangement of cerebral metabolism, including systemic infection, poisoning, drug intoxication or withdrawal, seizures or head trauma, and metabolic disturbances such as hypoxia, hypoglycaemia, fluid, electrolyte, or acid-base imbalances, or hepatic or renal failure. Called also acute confusional state and acute brain syndrome. [EU] Delivery of Health Care: The concept concerned with all aspects of providing and distributing health services to a patient population. [NIH] Delusions: A false belief regarding the self or persons or objects outside the self that persists despite the facts, and is not considered tenable by one's associates. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive
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stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Dendritic cell: A special type of antigen-presenting cell (APC) that activates T lymphocytes. [NIH]
Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Amalgam: An alloy used in restorative dentistry that contains mercury, silver, tin, copper, and possibly zinc. [NIH] Dentate Gyrus: Gray matter situated above the gyrus hippocampi. It is composed of three layers. The molecular layer is continuous with the hippocampus in the hippocampal fissure. The granular layer consists of closely arranged spherical or oval neurons, called granule cells, whose axons pass through the polymorphic layer ending on the dendrites of pyramidal cells in the hippocampus. [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Depressive Disorder: An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent. [NIH] Deprivation: Loss or absence of parts, organs, powers, or things that are needed. [EU] Dermal: Pertaining to or coming from the skin. [NIH] Dermatitis: Any inflammation of the skin. [NIH] Dermis: A layer of vascular connective tissue underneath the epidermis. The surface of the dermis contains sensitive papillae. Embedded in or beneath the dermis are sweat glands, hair follicles, and sebaceous glands. [NIH] DES: Diethylstilbestrol. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [NIH] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] Detoxification: Treatment designed to free an addict from his drug habit. [EU] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Developed Countries: Countries that have reached a level of economic achievement through an increase of production, per capita income and consumption, and utilization of natural and human resources. [NIH] Developing Countries: Countries in the process of change directed toward economic growth, that is, an increase in production, per capita consumption, and income. The process of economic growth involves better utilization of natural and human resources, which results in a change in the social, political, and economic structures. [NIH] Dextroamphetamine: The d-form of amphetamine. It is a central nervous system stimulant and a sympathomimetic. It has also been used in the treatment of narcolepsy and of attention deficit disorders and hyperactivity in children. Dextroamphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulating release of monamines, and inhibiting monoamine oxidase. It is also a drug of abuse and a
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psychotomimetic. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diabetic Retinopathy: Retinopathy associated with diabetes mellitus, which may be of the background type, progressively characterized by microaneurysms, interretinal punctuate macular edema, or of the proliferative type, characterized by neovascularization of the retina and optic disk, which may project into the vitreous, proliferation of fibrous tissue, vitreous hemorrhage, and retinal detachment. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diastole: Period of relaxation of the heart, especially the ventricles. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH] Dietary Fats: Fats present in food, especially in animal products such as meat, meat products, butter, ghee. They are present in lower amounts in nuts, seeds, and avocados. [NIH]
Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Dilatation: The act of dilating. [NIH] Dilator: A device used to stretch or enlarge an opening. [NIH] Dilution: A diluted or attenuated medicine; in homeopathy, the diffusion of a given quantity of a medicinal agent in ten or one hundred times the same quantity of water. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [NIH] Discrimination: The act of qualitative and/or quantitative differentiation between two or more stimuli. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Dispenser: Glass, metal or plastic shell fitted with valve from which a pressurized formulation is dispensed; an instrument for atomizing. [NIH] Dissection: Cutting up of an organism for study. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration
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in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Diuresis: Increased excretion of urine. [EU] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Dopa: The racemic or DL form of DOPA, an amino acid found in various legumes. The dextro form has little physiologic activity but the levo form (levodopa) is a very important physiologic mediator and precursor and pharmacological agent. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dosage Forms: Completed forms of the pharmaceutical preparation in which prescribed doses of medication are included. They are designed to resist action by gastric fluids, prevent vomiting and nausea, reduce or alleviate the undesirable taste and smells associated with oral administration, achieve a high concentration of drug at target site, or produce a delayed or long-acting drug effect. They include capsules, liniments, ointments, pharmaceutical solutions, powders, tablets, etc. [NIH] Dose-dependent: Refers to the effects of treatment with a drug. If the effects change when the dose of the drug is changed, the effects are said to be dose dependent. [NIH] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] Doxepin: A dibenzoxepin tricyclic compound. It displays a range of pharmacological actions including maintaining adrenergic innervation. Its mechanism of action is not fully understood, but it appears to block reuptake of monoaminergic neurotransmitters into presynaptic terminals. It also possesses anticholinergic activity and modulates antagonism of histamine H(1)- and H(2)-receptors. [NIH] Drinking Behavior: Behaviors associated with the ingesting of water and other liquids; includes rhythmic patterns of drinking (time intervals - onset and duration), frequency and satiety. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Delivery Systems: Systems of administering drugs through controlled delivery so that an optimum amount reaches the target site. Drug delivery systems encompass the carrier, route, and target. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH]
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Duct: A tube through which body fluids pass. [NIH] Duodenum: The first part of the small intestine. [NIH] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dyskinesia: Impairment of the power of voluntary movement, resulting in fragmentary or incomplete movements. [EU] Dysphoric: A feeling of unpleasantness and discomfort. [NIH] Dystonia: Disordered tonicity of muscle. [EU] Dystrophic: Pertaining to toxic habitats low in nutrients. [NIH] Eczema: A pruritic papulovesicular dermatitis occurring as a reaction to many endogenous and exogenous agents (Dorland, 27th ed). [NIH] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Eicosanoids: A class of oxygenated, endogenous, unsaturated fatty acids derived from arachidonic acid. They include prostaglandins, leukotrienes, thromboxanes, and hydroxyeicosatetraenoic acid compounds (HETE). They are hormone-like substances that act near the site of synthesis without altering functions throughout the body. [NIH] Ejaculation: The release of semen through the penis during orgasm. [NIH] Elasticity: Resistance and recovery from distortion of shape. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electrocardiogram: Measurement of electrical activity during heartbeats. [NIH] Electrolysis: Destruction by passage of a galvanic electric current, as in disintegration of a chemical compound in solution. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU] Electroplating: Coating with a metal or alloy by electrolysis. [NIH] Emaciation: Clinical manifestation of excessive leanness usually caused by disease or a lack of nutrition. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryo Transfer: Removal of a mammalian embryo from one environment and replacement in the same or a new environment. The embryo is usually in the pre-nidation phase, i.e., a blastocyst. The process includes embryo or blastocyst transplantation or
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transfer after in vitro fertilization and transfer of the inner cell mass of the blastocyst. It is not used for transfer of differentiated embryonic tissue, e.g., germ layer cells. [NIH] Embryology: The study of the development of an organism during the embryonic and fetal stages of life. [NIH] Emollient: Softening or soothing; called also malactic. [EU] Emphysema: A pathological accumulation of air in tissues or organs. [NIH] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endometrium: The layer of tissue that lines the uterus. [NIH] Endorphins: One of the three major groups of endogenous opioid peptides. They are large peptides derived from the pro-opiomelanocortin precursor. The known members of this group are alpha-, beta-, and gamma-endorphin. The term endorphin is also sometimes used to refer to all opioid peptides, but the narrower sense is used here; opioid peptides is used for the broader group. [NIH] Endoscopy: Endoscopic examination, therapy or surgery performed on interior parts of the body. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium, Lymphatic: Unbroken cellular lining (intima) of the lymph vessels (e.g., the high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have filtered through the capillaries into the tissue spaces. [NIH] Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components from interstitium to lumen; this function has been most intensively studied in the blood capillaries. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxins: Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. [NIH]
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Energy balance: Energy is the capacity of a body or a physical system for doing work. Energy balance is the state in which the total energy intake equals total energy needs. [NIH] Enhancers: Transcriptional element in the virus genome. [NIH] Enkephalin: A natural opiate painkiller, in the hypothalamus. [NIH] Enteric-coated: A term designating a special coating applied to tablets or capsules which prevents release and absorption of their contents until they reach the intestines. [EU] Enteritis: Inflammation of the intestine, applied chiefly to inflammation of the small intestine; see also enterocolitis. [EU] Entorhinal Cortex: Cortex where the signals are combined with those from other sensory systems. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]
Environmental tobacco smoke: ETS. Smoke that comes from the burning of a tobacco product and smoke that is exhaled by smokers (second-hand smoke). Inhaling ETS is called involuntary or passive smoking. [NIH] Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epidermoid carcinoma: A type of cancer in which the cells are flat and look like fish scales. Also called squamous cell carcinoma. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Erectile: The inability to get or maintain an erection for satisfactory sexual intercourse. Also called impotence. [NIH] Erection: The condition of being made rigid and elevated; as erectile tissue when filled with blood. [EU] ERV: The expiratory reserve volume is the largest volume of gas that can be expired from the end-expiratory level. [NIH] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may
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result from a variety of causes. [NIH] Erythrocyte Indices: Quantification of size and cell hemoglobin content or concentration of the erythrocyte, usually derived from erythrocyte count, blood hemoglobin concentration, and hematocrit. Includes the mean cell volume (MCV), mean cell hemoglobin (MCH), and mean cell hemoglobin concentration (MCHC). Use also for cell diameter and thickness. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]
Estradiol: The most potent mammalian estrogenic hormone. It is produced in the ovary, placenta, testis, and possibly the adrenal cortex. [NIH] Estrogen: One of the two female sex hormones. [NIH] Estrogen receptor: ER. Protein found on some cancer cells to which estrogen will attach. [NIH]
Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Ethnic Groups: A group of people with a common cultural heritage that sets them apart from others in a variety of social relationships. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Euphoria: An exaggerated feeling of physical and emotional well-being not consonant with apparent stimuli or events; usually of psychologic origin, but also seen in organic brain disease and toxic states. [NIH] Evacuation: An emptying, as of the bowels. [EU] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Evoked Potentials: The electric response evoked in the central nervous system by stimulation of sensory receptors or some point on the sensory pathway leading from the receptor to the cortex. The evoked stimulus can be auditory, somatosensory, or visual, although other modalities have been reported. Event-related potentials is sometimes used synonymously with evoked potentials but is often associated with the execution of a motor, cognitive, or psychophysiological task, as well as with the response to a stimulus. [NIH] Excipient: Any more or less inert substance added to a prescription in order to confer a suitable consistency or form to the drug; a vehicle. [EU] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Expiration: The act of breathing out, or expelling air from the lungs. [EU] Expiratory: The volume of air which leaves the breathing organs in each expiration. [NIH]
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Expiratory Reserve Volume: The extra volume of air that can be expired with maximum effort beyond the level reached at the end of a normal, quiet expiration. Common abbreviation is ERV. [NIH] External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extraction: The process or act of pulling or drawing out. [EU] Extrapyramidal: Outside of the pyramidal tracts. [EU] Eye Movements: Voluntary or reflex-controlled movements of the eye. [NIH] Facial: Of or pertaining to the face. [EU] Facial Nerve: The 7th cranial nerve. The facial nerve has two parts, the larger motor root which may be called the facial nerve proper, and the smaller intermediate or sensory root. Together they provide efferent innervation to the muscles of facial expression and to the lacrimal and salivary glands, and convey afferent information for taste from the anterior two-thirds of the tongue and for touch from the external ear. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Family Practice: A medical specialty concerned with the provision of continuing, comprehensive primary health care for the entire family. [NIH] Family Relations: Behavioral, psychological, and social relations among various members of the nuclear family and the extended family. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]
Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Fermentation: An enzyme-induced chemical change in organic compounds that takes place in the absence of oxygen. The change usually results in the production of ethanol or lactic acid, and the production of energy. [NIH] Fertilization in Vitro: Fertilization of an egg outside the body when the egg is normally fertilized in the body. [NIH]
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Fertilizers: Substances or mixtures that are added to the soil to supply nutrients or to make available nutrients already present in the soil, in order to increase plant growth and productivity. [NIH] Fetal Blood: Blood of the fetus. Exchange of nutrients and waste between the fetal and maternal blood occurs via the placenta. The cord blood is blood contained in the umbilical vessels at the time of delivery. [NIH] Fetal Death: Death of the young developing in utero. [NIH] Fetal Development: Morphologic and physiologic growth and development of the mammalian embryo or fetus. [NIH] Fetal Growth Retardation: The failure of a fetus to attain its expected growth potential at any gestational stage. [NIH] Fetal Heart: The heart of the fetus of any viviparous animal. It refers to the heart in the postembryonic period and is differentiated from the embryonic heart (heart/embryology) only on the basis of time. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibroblast Growth Factor: Peptide isolated from the pituitary gland and from the brain. It is a potent mitogen which stimulates growth of a variety of mesodermal cells including chondrocytes, granulosa, and endothelial cells. The peptide may be active in wound healing and animal limb regeneration. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Filler: An inactive substance used to make a product bigger or easier to handle. For example, fillers are often used to make pills or capsules because the amount of active drug is too small to be handled conveniently. [NIH] Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU] Fissure: Any cleft or groove, normal or otherwise; especially a deep fold in the cerebral cortex which involves the entire thickness of the brain wall. [EU] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed
Dictionary 581
silver to form a permanent image. [EU] Flatus: Gas passed through the rectum. [NIH] Flavoring Agents: Substances added to foods and medicine to improve the quality of taste. [NIH]
Flicker Fusion: The point or frequency at which all flicker of an intermittent light stimulus disappears. [NIH] Flunitrazepam: Benzodiazepine with pharmacologic actions similar to those of diazepam. The United States Government has banned the importation of this drug. Steps are being taken to reclassify this substance as a Schedule 1 drug with no accepted medical use. [NIH] Fluorouracil: A pyrimidine analog that acts as an antineoplastic antimetabolite and also has immunosuppressant. It interferes with DNA synthesis by blocking the thymidylate synthetase conversion of deoxyuridylic acid to thymidylic acid. [NIH] Fluoxetine: The first highly specific serotonin uptake inhibitor. It is used as an antidepressant and often has a more acceptable side-effects profile than traditional antidepressants. [NIH] Fluphenazine: A phenothiazine used in the treatment of psychoses. Its properties and uses are generally similar to those of chlorpromazine. [NIH] Flushing: A transient reddening of the face that may be due to fever, certain drugs, exertion, stress, or a disease process. [NIH] Focus Groups: A method of data collection and a qualitative research tool in which a small group of individuals are brought together and allowed to interact in a discussion of their opinions about topics, issues, or questions. [NIH] Follicular Fluid: A fluid consisting of sex steroid hormones, plasma proteins, mucopolysaccharides, and electrolytes that is present in the vesicular ovarian follicle (Graafian follicle) surrounding the ovum. [NIH] Foramen: A natural hole of perforation, especially one in a bone. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fornix: A bundle of nerves connected to the hippocampus. [NIH] Forskolin: Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant Coleus forskohlii. Has antihypertensive, positive ionotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland. [NIH] Fractionation: Dividing the total dose of radiation therapy into several smaller, equal doses delivered over a period of several days. [NIH] Free Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. [NIH] Frontal Lobe: The anterior part of the cerebral hemisphere. [NIH] Frostbite: Damage to tissues as the result of low environmental temperatures. [NIH] Functional magnetic resonance imaging: A noninvasive tool used to observe functioning in the brain or other organs by detecting changes in chemical composition, blood flow, or both. [NIH]
Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or
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asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] GABA: The most common inhibitory neurotransmitter in the central nervous system. [NIH] Galanthamine: A cholinesterase inhibitor. It has been used to reverse the muscular effects of gallamine and tubocurarine and has been studied as a treatment for Alzheimer's disease and other central nervous system disorders. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Ganglionic Blockers: Agents having as their major action the interruption of neural transmission at nicotinic receptors on postganglionic autonomic neurons. Because their actions are so broad, including blocking of sympathetic and parasympathetic systems, their therapeutic use has been largely supplanted by more specific drugs. They may still be used in the control of blood pressure in patients with acute dissecting aortic aneurysm and for the induction of hypotension in surgery. [NIH] Gap Junctions: Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of connexins, the family of proteins which form the junctions. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Emptying: The evacuation of food from the stomach into the duodenum. [NIH] Gastric Mucosa: Surface epithelium in the stomach that invaginates into the lamina propria, forming gastric pits. Tubular glands, characteristic of each region of the stomach (cardiac, gastric, and pyloric), empty into the gastric pits. The gastric mucosa is made up of several different kinds of cells. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
Gastroenteritis: An acute inflammation of the lining of the stomach and intestines, characterized by anorexia, nausea, diarrhoea, abdominal pain, and weakness, which has various causes, including food poisoning due to infection with such organisms as Escherichia coli, Staphylococcus aureus, and Salmonella species; consumption of irritating food or drink; or psychological factors such as anger, stress, and fear. Called also enterogastritis. [EU] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gels: Colloids with a solid continuous phase and liquid as the dispersed phase; gels may be unstable when, due to temperature or other cause, the solid phase liquifies; the resulting colloid is called a sol. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]
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Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genital: Pertaining to the genitalia. [EU] Genitourinary: Pertaining to the genital and urinary organs; urogenital; urinosexual. [EU] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Gestational: Psychosis attributable to or occurring during pregnancy. [NIH] Gestational Age: Age of the conceptus. In humans, this may be assessed by medical history, physical examination, early immunologic pregnancy tests, radiography, ultrasonography, and amniotic fluid analysis. [NIH] Gingivitis: Inflammation of the gingivae. Gingivitis associated with bony changes is referred to as periodontitis. Called also oulitis and ulitis. [EU] Ginseng: An araliaceous genus of plants that contains a number of pharmacologically active agents used as stimulants, sedatives, and tonics, especially in traditional medicine. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glioblastoma: A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures. [NIH] Glioma: A cancer of the brain that comes from glial, or supportive, cells. [NIH] Glossopharyngeal Nerve: The 9th cranial nerve. The glossopharyngeal nerve is a mixed motor and sensory nerve; it conveys somatic and autonomic efferents as well as general, special, and visceral afferents. Among the connections are motor fibers to the stylopharyngeus muscle, parasympathetic fibers to the parotid glands, general and taste afferents from the posterior third of the tongue, the nasopharynx, and the palate, and afferents from baroreceptors and chemoreceptors of the carotid sinus. [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]
Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent.
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[NIH]
Glycerophospholipids: Derivatives of phosphatidic acid in which the hydrophobic regions are composed of two fatty acids and a polar alcohol is joined to the C-3 position of glycerol through a phosphodiester bond. They are named according to their polar head groups, such as phosphatidylcholine and phosphatidylethanolamine. [NIH] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins. [NIH] Gout: Hereditary metabolic disorder characterized by recurrent acute arthritis, hyperuricemia and deposition of sodium urate in and around the joints, sometimes with formation of uric acid calculi. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Granule: A small pill made from sucrose. [EU] Granulocyte: A type of white blood cell that fights bacterial infection. Neutrophils, eosinophils, and basophils are granulocytes. [NIH] Granulosa Cells: Cells of the membrana granulosa lining the vesicular ovarian follicle which become luteal cells after ovulation. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Habitual: Of the nature of a habit; according to habit; established by or repeated by force of habit, customary. [EU] Haematoma: A localized collection of blood, usually clotted, in an organ, space, or tissue, due to a break in the wall of a blood vessel. [EU] Hair follicles: Shafts or openings on the surface of the skin through which hair grows. [NIH] Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache,
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paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] Health Care Costs: The actual costs of providing services related to the delivery of health care, including the costs of procedures, therapies, and medications. It is differentiated from health expenditures, which refers to the amount of money paid for the services, and from fees, which refers to the amount charged, regardless of cost. [NIH] Health Education: Education that increases the awareness and favorably influences the attitudes and knowledge relating to the improvement of health on a personal or community basis. [NIH] Health Expenditures: The amounts spent by individuals, groups, nations, or private or public organizations for total health care and/or its various components. These amounts may or may not be equivalent to the actual costs (health care costs) and may or may not be shared among the patient, insurers, and/or employers. [NIH] Health Promotion: Encouraging consumer behaviors most likely to optimize health potentials (physical and psychosocial) through health information, preventive programs, and access to medical care. [NIH] Health Services: Services for the diagnosis and treatment of disease and the maintenance of health. [NIH] Hearing aid: A miniature, portable sound amplifier for persons with impaired hearing, consisting of a microphone, audio amplifier, earphone, and battery. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heartbeat: One complete contraction of the heart. [NIH] Heartburn: Substernal pain or burning sensation, usually associated with regurgitation of gastric juice into the esophagus. [NIH] Hematocrit: Measurement of the volume of packed red cells in a blood specimen by centrifugation. The procedure is performed using a tube with graduated markings or with automated blood cell counters. It is used as an indicator of erythrocyte status in disease. For example, anemia shows a low hematocrit, polycythemia, high values. [NIH] Hematopoiesis: The development and formation of various types of blood cells. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemodynamics: The movements of the blood and the forces involved in systemic or regional blood circulation. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels
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carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]
Hepatic: Refers to the liver. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Hippocampus: A curved elevation of gray matter extending the entire length of the floor of the temporal horn of the lateral ventricle (Dorland, 28th ed). The hippocampus, subiculum, and dentate gyrus constitute the hippocampal formation. Sometimes authors include the entorhinal cortex in the hippocampal formation. [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Homicide: The killing of one person by another. [NIH] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Horny layer: The superficial layer of the epidermis containing keratinized cells. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Human papillomavirus: HPV. A virus that causes abnormal tissue growth (warts) and is often associated with some types of cancer. [NIH] Hydrobromic Acid: Hydrobromic acid (HBr). A solution of hydrogen bromide gas in water. [NIH]
Hydrochloric Acid: A strong corrosive acid that is commonly used as a laboratory reagent. It is formed by dissolving hydrogen chloride in water. Gastric acid is the hydrochloric acid component of gastric juice. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Cyanide: HCN. A toxic liquid or colorless gas. It is found in the smoke of various tobacco products and released by combustion of nitrogen-containing organic materials. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrogenation: Specific method of reduction in which hydrogen is added to a substance by
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the direct use of gaseous hydrogen. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxylation: Hydroxylate, to introduce hydroxyl into (a compound or radical) usually by replacement of hydrogen. [EU] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hydroxyzine: A histamine H1 receptor antagonist that is effective in the treatment of chronic urticaria, dermatitis, and histamine-mediated pruritus. Unlike its major metabolite cetirizine, it does cause drowsiness. It is also effective as an antiemetic, for relief of anxiety and tension, and as a sedative. [NIH] Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [NIH] Hyperglycemia: Abnormally high blood sugar. [NIH] Hypericum: Genus of perennial plants in the family Clusiaceae (Hypericaceae). Herbal and homeopathic preparations are used for depression, neuralgias, and a variety of other conditions. Contains flavonoids, glycosides, mucilage, tannins, and volatile oils (oils, essential). [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypersensitivity, Immediate: Hypersensitivity reactions which occur within minutes of exposure to challenging antigen due to the release of histamine which follows the antigenantibody reaction and causes smooth muscle contraction and increased vascular permeability. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypnotic: A drug that acts to induce sleep. [EU] Hypochlorous Acid: HClO. An oxyacid of chlorine containing monovalent chlorine that acts as an oxidizing or reducing agent. [NIH] Hypokinesia: Slow or diminished movement of body musculature. It may be associated with basal ganglia diseases; mental disorders; prolonged inactivity due to illness; experimental protocols used to evaluate the physiologic effects of immobility; and other conditions. [NIH] Hypoplasia: Incomplete development or underdevelopment of an organ or tissue. [EU] Hypotension: Abnormally low blood pressure. [NIH] Hypothalamic: Of or involving the hypothalamus. [EU] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Hypoxemia: Deficient oxygenation of the blood; hypoxia. [EU] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU]
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Hypoxic: Having too little oxygen. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Ileum: The lower end of the small intestine. [NIH] Imipramine: The prototypical tricyclic antidepressant. It has been used in major depression, dysthymia, bipolar depression, attention-deficit disorders, agoraphobia, and panic disorders. It has less sedative effect than some other members of this therapeutic group. [NIH]
Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]
Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]
effects
of
foreign
Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunogen: A substance that is capable of causing antibody formation. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] Impotence: The inability to perform sexual intercourse. [NIH] Impregnation: 1. The act of fecundation or of rendering pregnant. 2. The process or act of saturation; a saturated condition. [EU] In situ: In the natural or normal place; confined to the site of origin without invasion of
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neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incidental: 1. Small and relatively unimportant, minor; 2. Accompanying, but not a major part of something; 3. (To something) Liable to occur because of something or in connection with something (said of risks, responsibilities, .) [EU] Incision: A cut made in the body during surgery. [NIH] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infant Mortality: Perinatal, neonatal, and infant deaths in a given population. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]
Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [NIH]
Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] In-line: A sexually-reproducing population derived from a common parentage. [NIH] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU]
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Inorganic: Pertaining to substances not of organic origin. [EU] Inotropic: Affecting the force or energy of muscular contractions. [EU] Inpatients: Persons admitted to health facilities which provide board and room, for the purpose of observation, care, diagnosis or treatment. [NIH] Insecticides: Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics. [NIH] Insomnia: Difficulty in going to sleep or getting enough sleep. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Intensive Care: Advanced and highly specialized care provided to medical or surgical patients whose conditions are life-threatening and require comprehensive care and constant monitoring. It is usually administered in specially equipped units of a health care facility. [NIH]
Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interindividual: Occurring between two or more individuals. [EU] Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU]
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Intracellular: Inside a cell. [NIH] Intracranial Hypertension: Increased pressure within the cranial vault. This may result from several conditions, including hydrocephalus; brain edema; intracranial masses; severe systemic hypertension; pseudotumor cerebri; and other disorders. [NIH] Intraocular: Within the eye. [EU] Intraocular pressure: Pressure of the fluid inside the eye; normal IOP varies among individuals. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]
Invertebrates: Animals that have no spinal column. [NIH] Involuntary: Reaction occurring without intention or volition. [NIH] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] Ion Exchange: Reversible chemical reaction between a solid, often an ION exchange resin, and a fluid whereby ions may be exchanged from one substance to another. This technique is used in water purification, in research, and in industry. [NIH] Ion Exchange Resins: High molecular weight, insoluble polymers which contain functional groups that are capable of undergoing exchange reactions (ion exchange) with either cations or anions. [NIH] Ionization: 1. Any process by which a neutral atom gains or loses electrons, thus acquiring a net charge, as the dissociation of a substance in solution into ions or ion production by the passage of radioactive particles. 2. Iontophoresis. [EU] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Irritants: Drugs that act locally on cutaneous or mucosal surfaces to produce inflammation; those that cause redness due to hyperemia are rubefacients; those that raise blisters are vesicants and those that penetrate sebaceous glands and cause abscesses are pustulants; tear gases and mustard gases are also irritants. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Isoniazid: Antibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis. [NIH]
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Jejunum: That portion of the small intestine which extends from the duodenum to the ileum; called also intestinum jejunum. [EU] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kava: Dried rhizome and roots of Piper methysticum, a shrub native to Oceania and known for its anti-anxiety and sedative properties. Heavy usage results in some adverse effects. It contains alkaloids, lactones, kawain, methysticin, mucilage, starch, and yangonin. Kava is also the name of the pungent beverage prepared from the plant's roots. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keratin: A class of fibrous proteins or scleroproteins important both as structural proteins and as keys to the study of protein conformation. The family represents the principal constituent of epidermis, hair, nails, horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms an alpha-helix, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. [NIH] Keratinocytes: Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. [NIH] Keto: It consists of 8 carbon atoms and within the endotoxins, it connects poysaccharide and lipid A. [NIH] Kinetic: Pertaining to or producing motion. [EU] Lactation: The period of the secretion of milk. [EU] Laminin: Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Lavage: A cleaning of the stomach and colon. Uses a special drink and enemas. [NIH] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]
Leptin: A 16-kD peptide hormone secreted from white adipocytes and implicated in the regulation of food intake and energy balance. Leptin provides the key afferent signal from fat cells in the feedback system that controls body fat stores. [NIH] Leucine: An essential branched-chain amino acid important for hemoglobin formation. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH]
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Leukotrienes: A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system. [NIH] Levamisole: An antiparasitic drug that is also being studied in cancer therapy with fluorouracil. [NIH] Levodopa: The naturally occurring form of dopa and the immediate precursor of dopamine. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to dopamine. It is used for the treatment of parkinsonism and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system. [NIH] Libido: The psychic drive or energy associated with sexual instinct in the broad sense (pleasure and love-object seeking). It may also connote the psychic energy associated with instincts in general that motivate behavior. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]
Life cycle: The successive stages through which an organism passes from fertilized ovum or spore to the fertilized ovum or spore of the next generation. [NIH] Life Expectancy: A figure representing the number of years, based on known statistics, to which any person of a given age may reasonably expect to live. [NIH] Ligaments: Shiny, flexible bands of fibrous tissue connecting together articular extremities of bones. They are pliant, tough, and inextensile. [NIH] Ligands: A RNA simulation method developed by the MIT. [NIH] Limbic: Pertaining to a limbus, or margin; forming a border around. [EU] Limbic System: A set of forebrain structures common to all mammals that is defined functionally and anatomically. It is implicated in the higher integration of visceral, olfactory, and somatic information as well as homeostatic responses including fundamental survival behaviors (feeding, mating, emotion). For most authors, it includes the amygdala, epithalamus, gyrus cinguli, hippocampal formation (see hippocampus), hypothalamus, parahippocampal gyrus, septal nuclei, anterior nuclear group of thalamus, and portions of the basal ganglia. (Parent, Carpenter's Human Neuroanatomy, 9th ed, p744; NeuroNames, http://rprcsgi.rprc.washington.edu/neuronames/index.html (September 2, 1998)). [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lip: Either of the two fleshy, full-blooded margins of the mouth. [NIH] Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipolysis: The hydrolysis of lipids. [NIH] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol,
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and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Lithium: An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight 6.94. Salts of lithium are used in treating manic-depressive disorders. [NIH]
Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] Lobeline: An alkaloid that has actions similar to nicotine on nicotinic cholinergic receptors but is less potent. It has been proposed for a variety of therapeutic uses including in respiratory disorders, peripheral vascular disorders, insomnia, and smoking cessation. [NIH] Local Government: Smallest political subdivisions within a country at which general governmental functions are carried-out. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Locomotor: Of or pertaining to locomotion; pertaining to or affecting the locomotive apparatus of the body. [EU] Long-Term Potentiation: A persistent increase in synaptic efficacy, usually induced by appropriate activation of the same synapses. The phenomenological properties of long-term potentiation suggest that it may be a cellular mechanism of learning and memory. [NIH] Lorazepam: An anti-anxiety agent with few side effects. It also has hypnotic, anticonvulsant, and considerable sedative properties and has been proposed as a preanesthetic agent. [NIH] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Lower Esophageal Sphincter: The muscle between the esophagus and stomach. When a person swallows, this muscle relaxes to let food pass from the esophagus to the stomach. It stays closed at other times to keep stomach contents from flowing back into the esophagus. [NIH]
Lubricants: Oily or slippery substances. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]
Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH]
Dictionary 595
Lymphocyte Count: A count of the number of lymphocytes in the blood. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Magnesium Hydroxide: Magnesium hydroxide (Mg(OH)2). An inorganic compound that occurs in nature as the mineral brucite. It acts as an antacid with cathartic effects. [NIH] Magnesium Oxide: Magnesium oxide (MgO). An inorganic compound that occurs in nature as the mineral periclase. In aqueous media combines quickly with water to form magnesium hydroxide. It is used as an antacid and mild laxative and has many nonmedicinal uses. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Maintenance therapy: Treatment that is given to help a primary (original) treatment keep working. Maintenance therapy is often given to help keep cancer in remission. [NIH] Malformation: A morphologic developmental process. [EU]
defect
resulting
from
an
intrinsically
abnormal
Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]
Mandible: The largest and strongest bone of the face constituting the lower jaw. It supports the lower teeth. [NIH] Manic: Affected with mania. [EU] Manic-depressive psychosis: One of a group of psychotic reactions, fundamentally marked by severe mood swings and a tendency to remission and recurrence. [NIH] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Marital Status: A demographic parameter indicating a person's status with respect to marriage, divorce, widowhood, singleness, etc. [NIH] Mastication: The act and process of chewing and grinding food in the mouth. [NIH] Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. [NIH] Meat: The edible portions of any animal used for food including domestic mammals (the major ones being cattle, swine, and sheep) along with poultry, fish, shellfish, and game. [NIH]
Meat Products: Articles of food which are derived by a process of manufacture from any portion of carcasses of any animal used for food (e.g., head cheese, sausage, scrapple). [NIH] Meatus: A canal running from the internal auditory foramen through the petrous portion of the temporal bone. It gives passage to the facial and auditory nerves together with the auditory branch of the basilar artery and the internal auditory veins. [NIH]
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Mecamylamine: A nicotinic antagonist that is well absorbed from the gastrointestinal tract and crosses the blood-brain barrier. Mecamylamine has been used as a ganglionic blocker in treating hypertension, but, like most ganglionic blockers, is more often used now as a research tool. [NIH] Meconium: The thick green-to-black mucilaginous material found in the intestines of a fullterm fetus. It consists of secretions of the intestinal glands, bile pigments, fatty acids, amniotic fluid, and intrauterine debris. It constitutes the first stools passed by a newborn. [NIH]
Meconium Aspiration: Syndrome caused by sucking of thick meconium into the lungs, usually by term or post-term infants (often small for gestational age) either in utero or with first breath. The resultant small airway obstruction may produce respiratory distress, tachypnea, cyanosis, pneumothorax, and/or pneumomediastinum. [NIH] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medicament: A medicinal substance or agent. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells. [NIH] Membrane Lipids: Lipids, predominantly phospholipids, cholesterol and small amounts of glycolipids found in membranes including cellular and intracellular membranes. These lipids may be arranged in bilayers in the membranes with integral proteins between the layers and peripheral proteins attached to the outside. Membrane lipids are required for active transport, several enzymatic activities and membrane formation. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Menopause: Permanent cessation of menstruation. [NIH] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior
Dictionary 597
producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Processes: Conceptual functions or thinking in all its forms. [NIH] Menthol: An alcohol produced from mint oils or prepared synthetically. [NIH] Mercury: A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to mercury poisoning. Because of its toxicity, the clinical use of mercury and mercurials is diminishing. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Mesoderm: The middle germ layer of the embryo. [NIH] Mesolimbic: Inner brain region governing emotion and drives. [NIH] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metabolization: The chemical process by which matter is broken down into simpler substances, said especially of food processed by the human body. [EU] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] Methylphenidate: A central nervous system stimulant used most commonly in the treatment of attention-deficit disorders in children and for narcolepsy. Its mechanisms appear to be similar to those of dextroamphetamine. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microglia: The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living
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organisms, they are sometimes classified as microorganisms. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microsomal: Of or pertaining to microsomes : vesicular fragments of endoplasmic reticulum formed after disruption and centrifugation of cells. [EU] Microspheres: Small uniformly-sized spherical particles frequently radioisotopes or various reagents acting as tags or markers. [NIH]
labeled
with
Microwaves: That portion of the electromagnetic spectrum lying between UHF (ultrahigh frequency) radio waves and heat (infrared) waves. Microwaves are used to generate heat, especially in some types of diathermy. They may cause heat damage to tissues. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Milligram: A measure of weight. A milligram is approximately 450,000-times smaller than a pound and 28,000-times smaller than an ounce. [NIH] Milliliter: A measure of volume for a liquid. A milliliter is approximately 950-times smaller than a quart and 30-times smaller than a fluid ounce. A milliliter of liquid and a cubic centimeter (cc) of liquid are the same. [NIH] Minocycline: A semisynthetic staphylococcus infections. [NIH]
antibiotic
effective
against
tetracycline-resistant
Minority Groups: A subgroup having special characteristics within a larger group, often bound together by special ties which distinguish it from the larger group. [NIH] Miscarriage: Spontaneous expulsion of the products of pregnancy before the middle of the second trimester. [NIH] Miscible: Susceptible of being mixed. [EU] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mobilization: The process of making a fixed part or stored substance mobile, as by separating a part from surrounding structures to make it accessible for an operative procedure or by causing release into the circulation for body use of a substance stored in the body. [EU] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU]
Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. [NIH] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH]
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Monoamine: Enzyme that breaks down dopamine in the astrocytes and microglia. [NIH] Monoamine Oxidase: An enzyme that catalyzes the oxidative deamination of naturally occurring monoamines. It is a flavin-containing enzyme that is localized in mitochondrial membranes, whether in nerve terminals, the liver, or other organs. Monoamine oxidase is important in regulating the metabolic degradation of catecholamines and serotonin in neural or target tissues. Hepatic monoamine oxidase has a crucial defensive role in inactivating circulating monoamines or those, such as tyramine, that originate in the gut and are absorbed into the portal circulation. (From Goodman and Gilman's, The Pharmacological Basis of Therapeutics, 8th ed, p415) EC 1.4.3.4. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monocyte: A type of white blood cell. [NIH] Mononuclear: A cell with one nucleus. [NIH] Mood Disorders: Those disorders that have a disturbance in mood as their predominant feature. [NIH] Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. [NIH] Morphological: Relating to the configuration or the structure of live organs. [NIH] Motility: The ability to move spontaneously. [EU] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Mouth Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Movement Disorders: Syndromes which feature dyskinesias as a cardinal manifestation of the disease process. Included in this category are degenerative, hereditary, post-infectious, medication-induced, post-inflammatory, and post-traumatic conditions. [NIH] Mucilaginous: Pertaining to or secreting mucus. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Mustard Gas: Severe irritant and vesicant of skin, eyes, and lungs. It may cause blindness and lethal lung edema and was formerly used as a war gas. The substance has been proposed as a cytostatic and for treatment of psoriasis. It has been listed as a known carcinogen in the Fourth Annual Report on Carcinogens (NTP-85-002, 1985) (Merck, 11th ed). [NIH] Mutagen: Any agent, such as X-rays, gamma rays, mustard gas, TCDD, that can cause abnormal mutation in living cells; having the power to cause mutations. [NIH] Mutagenic: Inducing genetic mutation. [EU] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myelogenous: Produced by, or originating in, the bone marrow. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardial Ischemia: A disorder of cardiac function caused by insufficient blood flow to
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the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (coronary arteriosclerosis), to obstruction by a thrombus (coronary thrombosis), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (myocardial infarction). [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myometrium: The smooth muscle coat of the uterus, which forms the main mass of the organ. [NIH] Myristate: Pharmacological activator of protein kinase C. [NIH] Naive: Used to describe an individual who has never taken a certain drug or class of drugs (e. g., AZT-naive, antiretroviral-naive), or to refer to an undifferentiated immune system cell. [NIH] Naloxone: A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors. [NIH] Naltrexone: Derivative of noroxymorphone that is the N-cyclopropylmethyl congener of naloxone. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. The FDA has approved naltrexone for the treatment of alcohol dependence. [NIH] Narcolepsy: A condition of unknown cause characterized by a periodic uncontrollable tendency to fall asleep. [NIH] Narcosis: A general and nonspecific reversible depression of neuronal excitability, produced by a number of physical and chemical aspects, usually resulting in stupor. [NIH] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [EU] Nasal Cavity: The proximal portion of the respiratory passages on either side of the nasal septum, lined with ciliated mucosa, extending from the nares to the pharynx. [NIH] Nasal Mucosa: The mucous membrane lining the nasal cavity. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasm: A new growth of benign or malignant tissue. [NIH] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nerve Endings: Specialized terminations of peripheral neurons. Nerve endings include neuroeffector junction(s) by which neurons activate target organs and sensory receptors which transduce information from the various sensory modalities and send it centrally in
Dictionary 601
the nervous system. Presynaptic nerve endings are presynaptic terminals. [NIH] Nerve Growth Factor: Nerve growth factor is the first of a series of neurotrophic factors that were found to influence the growth and differentiation of sympathetic and sensory neurons. It is comprised of alpha, beta, and gamma subunits. The beta subunit is responsible for its growth stimulating activity. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neuroblastoma: Cancer that arises in immature nerve cells and affects mostly infants and children. [NIH] Neuroeffector Junction: The synapse between a neuron (presynaptic) and an effector cell other than another neuron (postsynaptic). Neuroeffector junctions include synapses onto muscles and onto secretory cells. [NIH] Neuroendocrine: Having to do with the interactions between the nervous system and the endocrine system. Describes certain cells that release hormones into the blood in response to stimulation of the nervous system. [NIH] Neurofilaments: Bundle of neuronal fibers. [NIH] Neuroleptic: A term coined to refer to the effects on cognition and behaviour of antipsychotic drugs, which produce a state of apathy, lack of initiative, and limited range of emotion and in psychotic patients cause a reduction in confusion and agitation and normalization of psychomotor activity. [EU] Neurologic: Having to do with nerves or the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Blocking Agents: Drugs that interrupt transmission of nerve impulses at the skeletal neuromuscular junction. They can be of two types, competitive, stabilizing blockers (neuromuscular nondepolarizing agents) or noncompetitive, depolarizing agents (neuromuscular depolarizing agents). Both prevent acetylcholine from triggering the muscle contraction and they are used as anesthesia adjuvants, as relaxants during electroshock, in convulsive states, etc. [NIH] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neuropeptide: A member of a class of protein-like molecules made in the brain. Neuropeptides consist of short chains of amino acids, with some functioning as neurotransmitters and some functioning as hormones. [NIH] Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH] Neuropsychological Tests: Tests designed to assess neurological function associated with certain behaviors. They are used in diagnosing brain dysfunction or damage and central nervous system disorders or injury. [NIH] Neurotic: 1. Pertaining to or characterized by neurosis. 2. A person affected with a neurosis.
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[EU]
Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]
Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophil: A type of white blood cell. [NIH] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Nickel: A trace element with the atomic symbol Ni, atomic number 28, and atomic weight 58.69. It is a cofactor of the enzyme urease. [NIH] Nicotine: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. [NIH] Nicotinic Agonists: Drugs that bind to and activate nicotinic cholinergic receptors (receptors, nicotinic). Nicotinic agonists act at postganglionic nicotinic receptors, at neuroeffector junctions in the peripheral nervous system, and at nicotinic receptors in the central nervous system. Agents that function as neuromuscular depolarizing blocking agents are included here because they activate nicotinic receptors, although they are used clinically to block nicotinic transmission. [NIH] Nicotinic Antagonists: Drugs that bind to nicotinic cholinergic receptors (receptors, nicotinic) and block the actions of acetylcholine or cholinergic agonists. Nicotinic antagonists block synaptic transmission at autonomic ganglia, the skeletal neuromuscular junction, and at central nervous system nicotinic synapses. [NIH] Nifedipine: A potent vasodilator agent with calcium antagonistic action. It is a useful antianginal agent that also lowers blood pressure. The use of nifedipine as a tocolytic is being investigated. [NIH] Nitric acid: A toxic, corrosive, colorless liquid used to make fertilizers, dyes, explosives, and other chemicals. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]
Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14.
Dictionary 603
Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Nitrogen Dioxide: Nitrogen oxide (NO2). A highly poisonous gas. Exposure produces inflammation of lungs that may only cause slight pain or pass unnoticed, but resulting edema several days later may cause death. (From Merck, 11th ed) It is a major atmospheric pollutant that is able to absorb UV light that does not reach the earth's surface. [NIH] Nitrogen Oxides: Inorganic oxides that contain nitrogen. [NIH] Nitroglycerin: A highly volatile organic nitrate that acts as a dilator of arterial and venous smooth muscle and is used in the treatment of angina. It provides relief through improvement of the balance between myocardial oxygen supply and demand. Although total coronary blood flow is not increased, there is redistribution of blood flow in the heart when partial occlusion of coronary circulation is effected. [NIH] Nitrosamines: A class of compounds that contain a -NH2 and a -NO radical. Many members of this group have carcinogenic and mutagenic properties. [NIH] Nitrous Oxide: Nitrogen oxide (N2O). A colorless, odorless gas that is used as an anesthetic and analgesic. High concentrations cause a narcotic effect and may replace oxygen, causing death by asphyxia. It is also used as a food aerosol in the preparation of whipping cream. [NIH]
Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Normotensive: 1. Characterized by normal tone, tension, or pressure, as by normal blood pressure. 2. A person with normal blood pressure. [EU] Nortriptyline: A metabolite of amitryptyline that is also used as an antidepressive agent. Nortriptyline is used in major depression, dysthymia, and atypical depressions. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclear Family: A family composed of spouses and their children. [NIH] Nuclear Medicine: A specialty field of radiology concerned with diagnostic, therapeutic, and investigative use of radioactive compounds in a pharmaceutical form. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleus Accumbens: Collection of pleomorphic cells in the caudal part of the anterior horn of the lateral ventricle, in the region of the olfactory tubercle, lying between the head of the caudate nucleus and the anterior perforated substance. It is part of the so-called ventral striatum, a composite structure considered part of the basal ganglia. [NIH] Obsessive-Compulsive Disorder: An anxiety disorder characterized by recurrent, persistent obsessions or compulsions. Obsessions are the intrusive ideas, thoughts, or images that are
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experienced as senseless or repugnant. Compulsions are repetitive and seemingly purposeful behavior which the individual generally recognizes as senseless and from which the individual does not derive pleasure although it may provide a release from tension. [NIH] Oculi: Globe or ball of the eye. [NIH] Odds Ratio: The ratio of two odds. The exposure-odds ratio for case control data is the ratio of the odds in favor of exposure among cases to the odds in favor of exposure among noncases. The disease-odds ratio for a cohort or cross section is the ratio of the odds in favor of disease among the exposed to the odds in favor of disease among the unexposed. The prevalence-odds ratio refers to an odds ratio derived cross-sectionally from studies of prevalent cases. [NIH] Odour: A volatile emanation that is perceived by the sense of smell. [EU] Office Visits: Visits made by patients to health service providers' offices for diagnosis, treatment, and follow-up. [NIH] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Olfaction: Function of the olfactory apparatus to perceive and discriminate between the molecules that reach it, in gas form from an external environment, directly or indirectly via the nose. [NIH] Oncology: The study of cancer. [NIH] Ondansetron: A competitive serotonin type 3 receptor antagonist. It is effective in the treatment of nausea and vomiting caused by cytotoxic chemotherapy drugs, including cisplatin, and it has reported anxiolytic and neuroleptic properties. [NIH] Oocytes: Female germ cells in stages between the prophase of the first maturation division and the completion of the second maturation division. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Opiate: A remedy containing or derived from opium; also any drug that induces sleep. [EU] Opium: The air-dried exudate from the unripe seed capsule of the opium poppy, Papaver somniferum, or its variant, P. album. It contains a number of alkaloids, but only a few morphine, codeine, and papaverine - have clinical significance. Opium has been used as an analgesic, antitussive, antidiarrheal, and antispasmodic. [NIH] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [NIH] Optic Disk: The portion of the optic nerve seen in the fundus with the ophthalmoscope. It is formed by the meeting of all the retinal ganglion cell axons as they enter the optic nerve. [NIH]
Orbicularis: A thin layer of fibers that originates at the posterior lacrimal crest and passes outward and forward, dividing into two slips which surround the canaliculi. [NIH] Orbit: One of the two cavities in the skull which contains an eyeball. Each eye is located in a bony socket or orbit. [NIH] Orbital: Pertaining to the orbit (= the bony cavity that contains the eyeball). [EU] Orthostatic: Pertaining to or caused by standing erect. [EU] Osmosis: Tendency of fluids (e.g., water) to move from the less concentrated to the more concentrated side of a semipermeable membrane. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a
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solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Ovarian Follicle: Spheroidal cell aggregation in the ovary containing an ovum. It consists of an external fibro-vascular coat, an internal coat of nucleated cells, and a transparent, albuminous fluid in which the ovum is suspended. [NIH] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Overdose: An accidental or deliberate dose of a medication or street drug that is in excess of what is normally used. [NIH] Ovulation: The discharge of a secondary oocyte from a ruptured graafian follicle. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Ovum Implantation: Endometrial implantation of the blastocyst. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]
Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). [NIH] Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxides: Binary compounds of oxygen containing the anion O(2-). The anion combines with metals to form alkaline oxides and non-metals to form acidic oxides. [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU] Palate: The structure that forms the roof of the mouth. It consists of the anterior hard palate and the posterior soft palate. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatitis: Acute or chronic inflammation of the pancreas, which may be asymptomatic or
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symptomatic, and which is due to autodigestion of a pancreatic tissue by its own enzymes. It is caused most often by alcoholism or biliary tract disease; less commonly it may be associated with hyperlipaemia, hyperparathyroidism, abdominal trauma (accidental or operative injury), vasculitis, or uraemia. [EU] Panic: A state of extreme acute, intense anxiety and unreasoning fear accompanied by disorganization of personality function. [NIH] Panic Disorder: A type of anxiety disorder characterized by unexpected panic attacks that last minutes or, rarely, hours. Panic attacks begin with intense apprehension, fear or terror and, often, a feeling of impending doom. Symptoms experienced during a panic attack include dyspnea or sensations of being smothered; dizziness, loss of balance or faintness; choking sensations; palpitations or accelerated heart rate; shakiness; sweating; nausea or other form of abdominal distress; depersonalization or derealization; paresthesias; hot flashes or chills; chest discomfort or pain; fear of dying and fear of not being in control of oneself or going crazy. Agoraphobia may also develop. Similar to other anxiety disorders, it may be inherited as an autosomal dominant trait. [NIH] Papillomavirus: A genus of Papovaviridae causing proliferation of the epithelium, which may lead to malignancy. A wide range of animals are infected including humans, chimpanzees, cattle, rabbits, dogs, and horses. [NIH] Paraganglia, Chromaffin: Small bodies containing chromaffin cells occurring outside of the adrenal medulla, most commonly near the sympathetic ganglia and in organs such as the kidney, liver, heart and gonads. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Parasympathomimetic: 1. Producing effects resembling those of stimulation of the parasympathetic nerve supply to a part. 2. An agent that produces effects similar to those produced by stimulation of the parasympathetic nerves. Called also cholinergic. [EU] Paresthesia: Subjective cutaneous sensations (e.g., cold, warmth, tingling, pressure, etc.) that are experienced spontaneously in the absence of stimulation. [NIH] Parkinsonism: A group of neurological disorders characterized by hypokinesia, tremor, and muscular rigidity. [EU] Paroxetine: A serotonin uptake inhibitor that is effective in the treatment of depression. [NIH]
Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]
Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Compliance: Voluntary cooperation of the patient in following a prescribed regimen. [NIH]
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Patient Education: The teaching or training of patients concerning their own health needs. [NIH]
Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Pemphigus: Group of chronic blistering diseases characterized histologically by acantholysis and blister formation within the epidermis. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] Perennial: Lasting through the year of for several years. [EU] Perforation: 1. The act of boring or piercing through a part. 2. A hole made through a part or substance. [EU] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] Periodicity: The tendency of a phenomenon to recur at regular intervals; in biological systems, the recurrence of certain activities (including hormonal, cellular, neural) may be annual, seasonal, monthly, daily, or more frequently (ultradian). [NIH] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Periodontal Ligament: Fibrous connective tissue surrounding the root of a tooth that separates it from and attaches it to the alveolar bone. [NIH] Periodontitis: Inflammation of the periodontal membrane; also called periodontitis simplex. [NIH]
Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peripheral Neuropathy: Nerve damage, usually affecting the feet and legs; causing pain, numbness, or a tingling feeling. Also called "somatic neuropathy" or "distal sensory polyneuropathy." [NIH] Peripheral Vascular Disease: Disease in the large blood vessels of the arms, legs, and feet. People who have had diabetes for a long time may get this because major blood vessels in their arms, legs, and feet are blocked and these limbs do not receive enough blood. The signs of PVD are aching pains in the arms, legs, and feet (especially when walking) and foot sores that heal slowly. Although people with diabetes cannot always avoid PVD, doctors say they have a better chance of avoiding it if they take good care of their feet, do not smoke, and keep both their blood pressure and diabetes under good control. [NIH]
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Peripheral vision: Side vision; ability to see objects and movement outside of the direct line of vision. [NIH] Peroxide: Chemical compound which contains an atom group with two oxygen atoms tied to each other. [NIH] Pest Control: The reduction or regulation of the population of noxious, destructive, or dangerous insects or other animals. [NIH] Pesticides: Chemicals used to destroy pests of any sort. The concept includes fungicides (industrial fungicides), insecticides, rodenticides, etc. [NIH] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. [NIH] Pharmaceutical Solutions: Homogeneous liquid preparations that contain one or more chemical substances dissolved, i.e., molecularly dispersed, in a suitable solvent or mixture of mutually miscible solvents. For reasons of their ingredients, method of preparation, or use, they do not fall into another group of products. [NIH] Pharmacodynamics: The study of the biochemical and physiological effects of drugs and the mechanisms of their actions, including the correlation of actions and effects of drugs with their chemical structure; also, such effects on the actions of a particular drug or drugs. [EU] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharmacotherapy: A regimen of using appetite suppressant medications to manage obesity by decreasing appetite or increasing the feeling of satiety. These medications decrease appetite by increasing serotonin or catecholamine—two brain chemicals that affect mood and appetite. [NIH] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenethyl isothiocyanate: PEITC. A naturally occurring compound found in some cruciferous vegetables. It is being studied as an agent to prevent cancer. [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phentolamine: A nonselective alpha-adrenergic antagonist. It is used in the treatment of hypertension and hypertensive emergencies, pheochromocytoma, vasospasm of Raynaud's disease and frostbite, clonidine withdrawal syndrome, impotence, and peripheral vascular disease. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phenylpropanolamine: A sympathomimetic that acts mainly by causing release of norepinephrine but also has direct agonist activity at some adrenergic receptors. It is most commonly used as a nasal vasoconstrictor and an appetite depressant. [NIH] Phorbol: Class of chemicals that promotes the development of tumors. [NIH]
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Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]
Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Physostigmine: A cholinesterase inhibitor that is rapidly absorbed through membranes. It can be applied topically to the conjunctiva. It also can cross the blood-brain barrier and is used when central nervous system effects are desired, as in the treatment of severe anticholinergic toxicity. [NIH] Pigments: Any normal or abnormal coloring matter in plants, animals, or micro-organisms. [NIH]
Pilot study: The initial study examining a new method or treatment. [NIH] Piper methysticum: For small images in peripheral vision, the product of intensity and the square root of the area stimulated is a constant for threshold effect. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Placebos: Any dummy medication or treatment. Although placebos originally were medicinal preparations having no specific pharmacological activity against a targeted condition, the concept has been extended to include treatments or procedures, especially those administered to control groups in clinical trials in order to provide baseline measurements for the experimental protocol. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Placental tissue: The tissue intervening between fetal blood and maternal blood in the placenta; it acts as a selective membrane regulating the passage of substances from the maternal to the fetal blood. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized
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destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Plasmin: A product of the lysis of plasminogen (profibrinolysin) by plasminogen activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. EC 3.4.21.7. [NIH] Plasminogen: Precursor of fibrinolysin (plasmin). It is a single-chain beta-globulin of molecular weight 80-90,000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent. [NIH] Plasminogen Activators: A heterogeneous group of proteolytic enzymes that convert plasminogen to plasmin. They are concentrated in the lysosomes of most cells and in the vascular endothelium, particularly in the vessels of the microcirculation. EC 3.4.21.-. [NIH] Plasticizers: Materials incorporated mechanically in plastics (usually PVC) to increase flexibility, workability or distensibility; due to the non-chemical inclusion, plasticizers leach out from the plastic and are found in body fluids and the general environment. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Pleomorphic: Occurring in various distinct forms. In terms of cells, having variation in the size and shape of cells or their nuclei. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Pneumothorax: Accumulation of air or gas in the space between the lung and chest wall, resulting in partial or complete collapse of the lung. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polyethylene: A vinyl polymer made from ethylene. It can be branched or linear. Branched or low-density polyethylene is tough and pliable but not to the same degree as linear polyethylene. Linear or high-density polyethylene has a greater hardness and tensile strength. Polyethylene is used in a variety of products, including implants and prostheses. [NIH]
Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., polypeptides,
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proteins, plastics). [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Porosity: Condition of having pores or open spaces. This often refers to bones, bone implants, or bone cements, but can refer to the porous state of any solid substance. [NIH] Port: An implanted device through which blood may be withdrawn and drugs may be infused without repeated needle sticks. Also called a port-a-cath. [NIH] Port-a-cath: An implanted device through which blood may be withdrawn and drugs may be infused without repeated needle sticks. Also called a port. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postoperative: After surgery. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-synaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-traumatic: Occurring as a result of or after injury. [EU] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potassium Channels: Cell membrane glycoproteins selective for potassium ions. [NIH] Potassium Cyanide: Potassium cyanide (K(CN)). A highly poisonous compound that is an inhibitor of many metabolic processes, but has been shown to be an especially potent inhibitor of heme enzymes and hemeproteins. It is used in many industrial processes. [NIH] Potentiate: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practicability: A non-standard characteristic of an analytical procedure. It is dependent on the scope of the method and is determined by requirements such as sample throughout and costs. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or
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symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Prefrontal Cortex: The rostral part of the frontal lobe, bounded by the inferior precentral fissure in humans, which receives projection fibers from the mediodorsal nucleus of the thalamus. The prefrontal cortex receives afferent fibers from numerous structures of the diencephalon, mesencephalon, and limbic system as well as cortical afferents of visual, auditory, and somatic origin. [NIH] Pregnancy Complications: The co-occurrence of pregnancy and a disease. The disease may precede or follow conception and it may or may not have a deleterious effect on the pregnant woman or fetus. [NIH] Pregnancy Outcome: Results of conception and ensuing pregnancy, including live birth, stillbirth, spontaneous abortion, induced abortion. The outcome may follow natural or artificial insemination or any of the various reproduction techniques, such as embryo transfer or fertilization in vitro. [NIH] Preload: The tension in the heart muscle at the end of diastole (before the contraction). [EU] Premedication: Preliminary administration of a drug preceding a diagnostic, therapeutic, or surgical procedure. The commonest types of premedication are antibiotics (antibiotic prophylaxis) and anti-anxiety agents. It does not include preanesthetic medication. [NIH] Premenstrual: Occurring before menstruation. [EU] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Presynaptic Terminals: The distal terminations of axons which are specialized for the release of neurotransmitters. Also included are varicosities along the course of axons which have similar specializations and also release transmitters. Presynaptic terminals in both the central and peripheral nervous systems are included. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Prickle: Several layers of the epidermis where the individual cells are connected by cell bridges. [NIH] Primary Sclerosing Cholangitis: Irritation, scarring, and narrowing of the bile ducts inside and outside the liver. Bile builds up in the liver and may damage its cells. Many people with this condition also have ulcerative colitis. [NIH] Private Sector: That distinct portion of the institutional, industrial, or economic structure of a country that is controlled or owned by non-governmental, private interests. [NIH] Proctocolitis: Inflammation of the rectum and colon. [NIH] Proctosigmoiditis: Irritation of the rectum and the sigmoid colon. [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU]
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Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Prone: Having the front portion of the body downwards. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Isoforms: Different forms of a protein that may be produced from different genes, or from the same gene by alternative splicing. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH]
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Proteoglycans: Glycoproteins which have a very high polysaccharide content. [NIH] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pruritic: Pertaining to or characterized by pruritus. [EU] Pruritus: An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. [NIH] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychoactive: Those drugs which alter sensation, mood, consciousness or other psychological or behavioral functions. [NIH] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Psychopharmacology: The study of the effects of drugs on mental and behavioral activity. [NIH]
Psychosis: A mental disorder characterized by gross impairment in reality testing as evidenced by delusions, hallucinations, markedly incoherent speech, or disorganized and agitated behaviour without apparent awareness on the part of the patient of the incomprehensibility of his behaviour; the term is also used in a more general sense to refer to mental disorders in which mental functioning is sufficiently impaired as to interfere grossly with the patient's capacity to meet the ordinary demands of life. Historically, the term has been applied to many conditions, e.g. manic-depressive psychosis, that were first described in psychotic patients, although many patients with the disorder are not judged psychotic. [EU] Psychotomimetic: Psychosis miming. [NIH] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH]
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Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Edema: An accumulation of an excessive amount of watery fluid in the lungs, may be caused by acute exposure to dangerous concentrations of irritant gasses. [NIH] Pulmonary Emphysema: Condition of the lungs characterized by increase beyond normal in the size of air spaces distal to the terminal bronchioles, either from dilatation of the alveoli or from destruction of their walls. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]
Purulent: Consisting of or containing pus; associated with the formation of or caused by pus. [EU] Pyoderma: Any purulent skin disease (Dorland, 27th ed). [NIH] Pyoderma Gangrenosum: An idiopathic, rapidly evolving, and severely debilitating disease occurring most commonly in association with chronic ulcerative colitis. It is characterized by the presence of boggy, purplish ulcers with undermined borders, appearing mostly on the legs. The majority of cases are in people between 40 and 60 years old. Its etiology is unknown. [NIH] Pyramidal Cells: Projection neurons in the cerebral cortex and the hippocampus. Pyramidal cells have a pyramid-shaped soma with the apex and an apical dendrite pointed toward the pial surface and other dendrites and an axon emerging from the base. The axons may have local collaterals but also project outside their cortical region. [NIH] Quaternary: 1. Fourth in order. 2. Containing four elements or groups. [EU] Quinpirole: A dopamine D2/D3 receptor agonist. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radio Waves: That portion of the electromagnetic spectrum beyond the microwaves, with wavelengths as high as 30 KM. They are used in communications, including television. Short Wave or HF (high frequency), UHF (ultrahigh frequency) and VHF (very high frequency) waves are used in citizen's band communication. [NIH] Radioactive: Giving off radiation. [NIH] Radioactivity: The quality of emitting or the emission of corpuscular or electromagnetic radiations consequent to nuclear disintegration, a natural property of all chemical elements of atomic number above 83, and possible of induction in all other known elements. [EU]
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Radioisotope: An unstable element that releases radiation as it breaks down. Radioisotopes can be used in imaging tests or as a treatment for cancer. [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Rage: Fury; violent, intense anger. [NIH] Raloxifene: A second generation selective estrogen receptor modulator (SERM) used to prevent osteoporosis in postmenopausal women. It has estrogen agonist effects on bone and cholesterol metabolism but behaves as a complete estrogen antagonist on mammary gland and uterine tissue. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Reaction Time: The time from the onset of a stimulus until the organism responds. [NIH] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Reality Testing: The individual's objective evaluation of the external world and the ability to differentiate adequately between it and the internal world; considered to be a primary ego function. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Muscarinic: One of the two major classes of cholinergic receptors. Muscarinic receptors were originally defined by their preference for muscarine over nicotine. There are several subtypes (usually M1, M2, M3.) that are characterized by their cellular actions, pharmacology, and molecular biology. [NIH] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Rectal: By or having to do with the rectum. The rectum is the last 8 to 10 inches of the large intestine and ends at the anus. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH]
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Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regional enteritis: Inflammation of the intestines, but usually only of the small intestine. Also called Crohn's disease. [NIH] Regurgitation: A backward flowing, as the casting up of undigested food, or the backward flowing of blood into the heart, or between the chambers of the heart when a valve is incompetent. [EU] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Relative risk: The ratio of the incidence rate of a disease among individuals exposed to a specific risk factor to the incidence rate among unexposed individuals; synonymous with risk ratio. Alternatively, the ratio of the cumulative incidence rate in the exposed to the cumulative incidence rate in the unexposed (cumulative incidence ratio). The term relative risk has also been used synonymously with odds ratio. This is because the odds ratio and relative risk approach each other if the disease is rare ( 5 percent of population) and the number of subjects is large. [NIH] Relaxant: 1. Lessening or reducing tension. 2. An agent that lessens tension. [EU] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal Circulation: The circulation of the blood through the vessels of the kidney. [NIH] Reproduction Techniques: Methods pertaining to the generation of new individuals. [NIH] Research Design: A plan for collecting and utilizing data so that desired information can be obtained with sufficient precision or so that an hypothesis can be tested properly. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respiratory Physiology: Functions and activities of the respiratory tract as a whole or of any of its parts. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin
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by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinoids: Derivatives of vitamin A. Used clinically in the treatment of severe cystic acne, psoriasis, and other disorders of keratinization. Their possible use in the prophylaxis and treatment of cancer is being actively explored. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Rhinitis: Inflammation of the mucous membrane of the nose. [NIH] Rhythmicity: Regular periodicity. [NIH] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Risperidone: A selective blocker of dopamine D2 and serotonin-5-HT-2 receptors that acts as an atypical antipsychotic agent. It has been shown to improve both positive and negative symptoms in the treatment of schizophrenia. [NIH] Rod: A reception for vision, located in the retina. [NIH] Rodenticides: Substances used to destroy or inhibit the action of rats, mice, or other rodents. [NIH]
Rubber: A high-molecular-weight polymeric elastomer derived from the milk juice (latex) of Hevea brasiliensis and other trees. It is a substance that can be stretched at room temperature to atleast twice its original length and after releasing the stress, retractrapidly, and recover its original dimensions fully. Synthetic rubber is made from many different chemicals, including styrene, acrylonitrile, ethylene, propylene, and isoprene. [NIH] Salicylic: A tuberculosis drug. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Salivation: 1. The secretion of saliva. 2. Ptyalism (= excessive flow of saliva). [EU] Saponin: A substance found in soybeans and many other plants. Saponins may help lower cholesterol and may have anticancer effects. [NIH] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a
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person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Scopolamine: An alkaloid from Solanaceae, especially Datura metel L. and Scopola carniolica. Scopolamine and its quaternary derivatives act as antimuscarinics like atropine, but may have more central nervous system effects. Among the many uses are as an anesthetic premedication, in urinary incontinence, in motion sickness, as an antispasmodic, and as a mydriatic and cycloplegic. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Sebaceous: Gland that secretes sebum. [NIH] Sebaceous gland: Gland that secretes sebum. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Secretory Vesicles: Vesicles derived from the golgi apparatus containing material to be released at the cell surface. [NIH] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] Segmental: Describing or pertaining to a structure which is repeated in similar form in successive segments of an organism, or which is undergoing segmentation. [NIH] Segmentation: The process by which muscles in the intestines move food and wastes through the body. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Selective estrogen receptor modulator: SERM. A drug that acts like estrogen on some tissues, but blocks the effect of estrogen on other tissues. Tamoxifen and raloxifene are SERMs. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Sensitization: 1. Administration of antigen to induce a primary immune response; priming; immunization. 2. Exposure to allergen that results in the development of hypersensitivity. 3. The coating of erythrocytes with antibody so that they are subject to lysis by complement in the presence of homologous antigen, the first stage of a complement fixation test. [EU] Sensor: A device designed to respond to physical stimuli such as temperature, light, magnetism or movement and transmit resulting impulses for interpretation, recording, movement, or operating control. [NIH] Septal: An abscess occurring at the root of the tooth on the proximal surface. [NIH]
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Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Sertraline: A selective serotonin uptake inhibitor that is used in the treatment of depression. [NIH]
Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Shame: An emotional attitude excited by realization of a shortcoming or impropriety. [NIH] Shivering: Involuntary contraction or twitching of the muscles. It is a physiologic method of heat production in man and other mammals. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]
Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Sigmoid: 1. Shaped like the letter S or the letter C. 2. The sigmoid colon. [EU] Sigmoid Colon: The lower part of the colon that empties into the rectum. [NIH] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Single Person: The unmarried man or woman. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH]
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Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Sleep apnea: A serious, potentially life-threatening breathing disorder characterized by repeated cessation of breathing due to either collapse of the upper airway during sleep or absence of respiratory effort. [NIH] Small cell lung cancer: A type of lung cancer in which the cells appear small and round when viewed under the microscope. Also called oat cell lung cancer. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smoking Cessation: Discontinuation of the habit of smoking, the inhaling and exhaling of tobacco smoke. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]
Snoring: Rough, noisy breathing during sleep, due to vibration of the uvula and soft palate. [NIH]
Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Social Support: Support systems that provide assistance and encouragement to individuals with physical or emotional disabilities in order that they may better cope. Informal social support is usually provided by friends, relatives, or peers, while formal assistance is provided by churches, groups, etc. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [NIH] Spatial disorientation: Loss of orientation in space where person does not know which way is up. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by
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refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Sphincter: A ringlike band of muscle fibres that constricts a passage or closes a natural orifice; called also musculus sphincter. [EU] Spike: The activation of synapses causes changes in the permeability of the dendritic membrane leading to changes in the membrane potential. This difference of the potential travels along the axon of the neuron and is called spike. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinous: Like a spine or thorn in shape; having spines. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Spontaneous Abortion: The non-induced birth of an embryo or of fetus prior to the stage of viability at about 20 weeks of gestation. [NIH] Squamous: Scaly, or platelike. [EU] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Stabilizer: A device for maintaining constant X-ray tube voltage or current. [NIH] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]
Staphylococcus: A genus of gram-positive, facultatively anaerobic, coccoid bacteria. Its organisms occur singly, in pairs, and in tetrads and characteristically divide in more than one plane to form irregular clusters. Natural populations of Staphylococcus are membranes of warm-blooded animals. Some species are opportunistic pathogens of humans and animals. [NIH] Stenosis: Narrowing or stricture of a duct or canal. [EU] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stillbirth: The birth of a dead fetus or baby. [NIH] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation.
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[EU]
Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stomatitis: Inflammation of the oral mucosa, due to local or systemic factors which may involve the buccal and labial mucosa, palate, tongue, floor of the mouth, and the gingivae. [EU]
Stool: The waste matter discharged in a bowel movement; feces. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stress management: A set of techniques used to help an individual cope more effectively with difficult situations in order to feel better emotionally, improve behavioral skills, and often to enhance feelings of control. Stress management may include relaxation exercises, assertiveness training, cognitive restructuring, time management, and social support. It can be delivered either on a one-to-one basis or in a group format. [NIH] Striatum: A higher brain's domain thus called because of its stripes. [NIH] Stricture: The abnormal narrowing of a body opening. Also called stenosis. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Stromal Cells: Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere. [NIH] Strychnine: An alkaloid found in the seeds of nux vomica. It is a competitive antagonist at glycine receptors and thus a convulsant. It has been used as an analeptic, in the treatment of nonketotic hyperglycinemia and sleep apnea, and as a rat poison. [NIH] Stupor: Partial or nearly complete unconsciousness, manifested by the subject's responding only to vigorous stimulation. Also, in psychiatry, a disorder marked by reduced responsiveness. [EU] Styrene: A colorless, toxic liquid with a strong aromatic odor. It is used to make rubbers, polymers and copolymers, and polystyrene plastics. [NIH] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Subiculum: A region of the hippocampus that projects to other areas of the brain. [NIH] Sublingual: Located beneath the tongue. [EU] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions
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of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]
Substrate: A substance upon which an enzyme acts. [EU] Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and methionine. [NIH] Sulfuric acid: A strong acid that, when concentrated is extemely corrosive to the skin and mucous membranes. It is used in making fertilizers, dyes, electroplating, and industrial explosives. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suppressive: Tending to suppress : effecting suppression; specifically : serving to suppress activity, function, symptoms. [EU] Sweat: The fluid excreted by the sweat glands. It consists of water containing sodium chloride, phosphate, urea, ammonia, and other waste products. [NIH] Sweat Glands: Sweat-producing structures that are embedded in the dermis. Each gland consists of a single tube, a coiled body, and a superficial duct. [NIH] Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Symptomatic treatment: Therapy that eases symptoms without addressing the cause of disease. [NIH] Symptomatology: 1. That branch of medicine with treats of symptoms; the systematic discussion of symptoms. 2. The combined symptoms of a disease. [EU] Synapse: The region where the processes of two neurons come into close contiguity, and the nervous impulse passes from one to the other; the fibers of the two are intermeshed, but, according to the general view, there is no direct contiguity. [NIH] Synapsis: The pairing between homologous chromosomes of maternal and paternal origin during the prophase of meiosis, leading to the formation of gametes. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU]
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Synaptic Transmission: The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors. These activated receptors modulate ion channels and/or secondmessenger systems to influence the postsynaptic cell. Electrical transmission is less common in the nervous system, and, as in other tissues, is mediated by gap junctions. [NIH] Synaptic Vesicles: Membrane-bound compartments which contain transmitter molecules. Synaptic vesicles are concentrated at presynaptic terminals. They actively sequester transmitter molecules from the cytoplasm. In at least some synapses, transmitter release occurs by fusion of these vesicles with the presynaptic membrane, followed by exocytosis of their contents. [NIH] Synaptosomes: Pinched-off nerve endings and their contents of vesicles and cytoplasm together with the attached subsynaptic area of the membrane of the post-synaptic cell. They are largely artificial structures produced by fractionation after selective centrifugation of nervous tissue homogenates. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Systolic blood pressure: The maximum pressure in the artery produced as the heart contracts and blood begins to flow. [NIH] Tachypnea: Rapid breathing. [NIH] Tacrine: A cholinesterase inhibitor that crosses the blood-brain barrier. Tacrine has been used to counter the effects of muscle relaxants, as a respiratory stimulant, and in the treatment of Alzheimer's disease and other central nervous system disorders. [NIH] Tardive: Marked by lateness, late; said of a disease in which the characteristic lesion is late in appearing. [EU] Taste Buds: Small sensory organs which contain gustatory receptor cells, basal cells, and supporting cells. Taste buds in humans are found in the epithelia of the tongue, palate, and pharynx. They are innervated by the chorda tympani nerve (a branch of the facial nerve) and the glossopharyngeal nerve. [NIH] Tear Gases: Gases that irritate the eyes, throat, or skin. Severe lacrimation develops upon irritation of the eyes. [NIH] Telencephalon: Paired anteriolateral evaginations of the prosencephalon plus the lamina terminalis. The cerebral hemispheres are derived from it. Many authors consider cerebrum a synonymous term to telencephalon, though a minority include diencephalon as part of the cerebrum (Anthoney, 1994). [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Temporal Lobe: Lower lateral part of the cerebral hemisphere. [NIH] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein
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synthesis. [NIH] Tetrodotoxin: Octahydro-12-(hydroxymethyl)-2-imino-5,9:7,10a-dimethano10aH(1,3)dioxocino(6,5-a)pyrimidine-4,7,10,11,12-pentol. An aminoperhydroquinazoline poison found mainly in the liver and ovaries of fishes in the order Tetradontiformes (pufferfish, globefish, toadfish), which are eaten. The toxin causes paresthesia and paralysis through interference with neuromuscular conduction. [NIH] Thalamus: Paired bodies containing mostly gray substance and forming part of the lateral wall of the third ventricle of the brain. The thalamus represents the major portion of the diencephalon and is commonly divided into cellular aggregates known as nuclear groups. [NIH]
Thermal: Pertaining to or characterized by heat. [EU] Thermogenesis: The generation of heat in order to maintain body temperature. The uncoupled oxidation of fatty acids contained within brown adipose tissue and shivering are examples of thermogenesis in mammals. [NIH] Third Ventricle: A narrow cleft inferior to the corpus callosum, within the diencephalon, between the paired thalami. Its floor is formed by the hypothalamus, its anterior wall by the lamina terminalis, and its roof by ependyma. It communicates with the fourth ventricle by the cerebral aqueduct, and with the lateral ventricles by the interventricular foramina. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytes: Blood cells that help prevent bleeding by causing blood clots to form. Also called platelets. [NIH] Thrombolytic: 1. Dissolving or splitting up a thrombus. 2. A thrombolytic agent. [EU] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]
Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH]
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Thyroid Hormones: Hormones secreted by the thyroid gland. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tic: An involuntary compulsive, repetitive, stereotyped movement, resembling a purposeful movement because it is coordinated and involves muscles in their normal synergistic relationships; tics usually involve the face and shoulders. [EU] Time Management: Planning and control of time to improve efficiency and effectiveness. [NIH]
Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic number 50, and atomic weight 118.71. [NIH] Tinnitus: Sounds that are perceived in the absence of any external noise source which may take the form of buzzing, ringing, clicking, pulsations, and other noises. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of cochlear diseases; vestibulocochlear nerve diseases; intracranial hypertension; craniocerebral trauma; and other conditions. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tobacco Industry: The aggregate business enterprise of agriculture, manufacture, and distribution related to tobacco and tobacco-derived products. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tone: 1. The normal degree of vigour and tension; in muscle, the resistance to passive elongation or stretch; tonus. 2. A particular quality of sound or of voice. 3. To make permanent, or to change, the colour of silver stain by chemical treatment, usually with a heavy metal. [EU] Tonic: 1. Producing and restoring the normal tone. 2. Characterized by continuous tension. 3. A term formerly used for a class of medicinal preparations believed to have the power of restoring normal tone to tissue. [EU] Tonus: A state of slight tension usually present in muscles even when they are not undergoing active contraction. [NIH] Tooth Loss: The failure to retain teeth as a result of disease or injury. [NIH] Topical: On the surface of the body. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living
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organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Tracer: A substance (such as a radioisotope) used in imaging procedures. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Transdermal: Entering through the dermis, or skin, as in administration of a drug applied to the skin in ointment or patch form. [EU] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Treatment Failure: A measure of the quality of health care by assessment of unsuccessful results of management and procedures used in combating disease, in individual cases or series. [NIH] Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, practicability, etc., of these interventions in individual cases or series. [NIH]
Trees: Woody, usually tall, perennial higher plants (Angiosperms, Gymnosperms, and some Pterophyta) having usually a main stem and numerous branches. [NIH] Tremor: Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of Parkinson disease. [NIH] Triacetin: A triglyceride that is used as an antifungal agent. [NIH] Tricyclic: Containing three fused rings or closed chains in the molecular structure. [EU] Trigeminal: Cranial nerve V. It is sensory for the eyeball, the conjunctiva, the eyebrow, the skin of face and scalp, the teeth, the mucous membranes in the mouth and nose, and is motor to the muscles of mastication. [NIH] Trigger zone: Dolorogenic zone (= producing or causing pain). [EU]
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Triglyceride: A lipid carried through the blood stream to tissues. Most of the body's fat tissue is in the form of triglycerides, stored for use as energy. Triglycerides are obtained primarily from fat in foods. [NIH] Trisomy: The possession of a third chromosome of any one type in an otherwise diploid cell. [NIH]
Trophoblast: The outer layer of cells of the blastocyst which works its way into the endometrium during ovum implantation and grows rapidly, later combining with mesoderm. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tryptophan Hydroxylase: An enzyme that catalyzes the hydroxylation of tryptophan to 5hydroxytryptophan in the presence of NADPH and molecular oxygen. It is important in the biosynthesis of serotonin. EC 1.14.16.4 [NIH] Tubercle: A rounded elevation on a bone or other structure. [NIH] Tuberculostatic: Inhibiting the growth of Mycobacterium tuberculosis. [EU] Tubocurarine: A neuromuscular blocker and active ingredient in curare; plant based alkaloid of Menispermaceae. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Tunica: A rather vague term to denote the lining coat of hollow organs, tubes, or cavities. [NIH]
Turpentine: The concrete oleoresin obtained from Pinus palustris Mill. (Pinaceae) and other species of Pinus. It contains a volatile oil, to which its properties are due, and to which form it is generally used. (Dorland, 28th ed) Turpentine is used as a solvent and an experimental irritant in biomedical research. Turpentine toxicity is of medical interest. [NIH] Type 2 diabetes: Usually characterized by a gradual onset with minimal or no symptoms of metabolic disturbance and no requirement for exogenous insulin. The peak age of onset is 50 to 60 years. Obesity and possibly a genetic factor are usually present. [NIH] Tyramine: An indirect sympathomimetic. Tyramine does not directly activate adrenergic receptors, but it can serve as a substrate for adrenergic uptake systems and monoamine oxidase so it prolongs the actions of adrenergic transmitters. It also provokes transmitter release from adrenergic terminals. Tyramine may be a neurotransmitter in some invertebrate nervous systems. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ulcerative colitis: Chronic inflammation of the colon that produces ulcers in its lining. This condition is marked by abdominal pain, cramps, and loose discharges of pus, blood, and mucus from the bowel. [NIH] Umbilical Arteries: Either of a pair of arteries originating from the internal iliac artery and passing through the umbilical cord to carry blood from the fetus to the placenta. [NIH] Umbilical Cord: The flexible structure, giving passage to the umbilical arteries and vein,
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which connects the embryo or fetus to the placenta. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Uraemia: 1. An excess in the blood of urea, creatinine, and other nitrogenous end products of protein and amino acids metabolism; more correctly referred to as azotemia. 2. In current usage the entire constellation of signs and symptoms of chronic renal failure, including nausea, vomiting anorexia, a metallic taste in the mouth, a uraemic odour of the breath, pruritus, uraemic frost on the skin, neuromuscular disorders, pain and twitching in the muscles, hypertension, edema, mental confusion, and acid-base and electrolyte imbalances. [EU]
Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [NIH] Urease: An enzyme that catalyzes the conversion of urea and water to carbon dioxide and ammonia. EC 3.5.1.5. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]
Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinate: To release urine from the bladder to the outside. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urogenital: Pertaining to the urinary and genital apparatus; genitourinary. [EU] Urticaria: A vascular reaction of the skin characterized by erythema and wheal formation due to localized increase of vascular permeability. The causative mechanism may be allergy, infection, or stress. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Uvula: Uvula palatinae; specifically, the tongue-like process which projects from the middle of the posterior edge of the soft palate. [NIH] Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vagus Nerve: The 10th cranial nerve. The vagus is a mixed nerve which contains somatic afferents (from skin in back of the ear and the external auditory meatus), visceral afferents (from the pharynx, larynx, thorax, and abdomen), parasympathetic efferents (to the thorax and abdomen), and efferents to striated muscle (of the larynx and pharynx). [NIH] Valerian: Valeriana officinale, an ancient, sedative herb of the large family Valerianaceae. The roots were formerly used to treat hysterias and other neurotic states and are presently used to treat sleep disorders. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasculitis: Inflammation of a blood vessel. [NIH] Vasodilator: An agent that widens blood vessels. [NIH]
Dictionary 631
Vasomotor: 1. Affecting the calibre of a vessel, especially of a blood vessel. 2. Any element or agent that effects the calibre of a blood vessel. [EU] VE: The total volume of gas either inspired or expired in one minute. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide back for gas exchange. [NIH] Venter: Belly. [NIH] Ventilation: 1. In respiratory physiology, the process of exchange of air between the lungs and the ambient air. Pulmonary ventilation (usually measured in litres per minute) refers to the total exchange, whereas alveolar ventilation refers to the effective ventilation of the alveoli, in which gas exchange with the blood takes place. 2. In psychiatry, verbalization of one's emotional problems. [EU] Ventral: 1. Pertaining to the belly or to any venter. 2. Denoting a position more toward the belly surface than some other object of reference; same as anterior in human anatomy. [EU] Ventral Tegmental Area: A region in the mesencephalon which is dorsomedial to the substantia nigra and ventral to the red nucleus. The mesocortical and mesolimbic dopaminergic systems originate here, including an important projection to the nucleus accumbens. Overactivity of the cells in this area has been suspected to contribute to the positive symptoms of schizophrenia. [NIH] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Vestibulocochlear Nerve: The 8th cranial nerve. The vestibulocochlear nerve has a cochlear part (cochlear nerve) which is concerned with hearing and a vestibular part (vestibular nerve) which mediates the sense of balance and head position. The fibers of the cochlear nerve originate from neurons of the spiral ganglion and project to the cochlear nuclei (cochlear nucleus). The fibers of the vestibular nerve arise from neurons of Scarpa's ganglion and project to the vestibular nuclei. [NIH] Vestibulocochlear Nerve Diseases: Diseases of the vestibular and/or cochlear (acoustic) nerves, which join to form the vestibulocochlear nerve. Vestibular neuritis, cochlear neuritis, and acoustic neuromas are relatively common conditions that affect these nerves. Clinical manifestations vary with which nerve is primarily affected, and include hearing loss, vertigo, and tinnitus. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Villi: The tiny, fingerlike projections on the surface of the small intestine. Villi help absorb nutrients. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or
632 Nicotine
viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visceral Afferents: The sensory fibers innervating the viscera. [NIH] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU] Vital Statistics: Used for general articles concerning statistics of births, deaths, marriages, etc. [NIH] Vitreous: Glasslike or hyaline; often used alone to designate the vitreous body of the eye (corpus vitreum). [EU] Vitreous Hemorrhage: Hemorrhage into the vitreous body. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Volition: Voluntary activity without external compulsion. [NIH] Vomica: The profuse and sudden expectoration of pus and putrescent matter. An abnormal cavity in an organ especially in the lung, caused by suppuration and the breaking down of tissue. [NIH] Vulgaris: An affection of the skin, especially of the face, the back and the chest, due to chronic inflammation of the sebaceous glands and the hair follicles. [NIH] War: Hostile conflict between organized groups of people. [NIH] Warts: Benign epidermal proliferations or tumors; some are viral in origin. [NIH] Weight Gain: Increase in body weight over existing weight. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]
Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Womb: A hollow, thick-walled, muscular organ in which the impregnated ovum is developed into a child. [NIH] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xanthine: An urinary calculus. [NIH] Xenobiotics: Chemical substances that are foreign to the biological system. They include naturally occurring compounds, drugs, environmental agents, carcinogens, insecticides, etc. [NIH]
Xenograft: The cells of one species transplanted to another species. [NIH]
Dictionary 633
X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zebrafish: A species of North American fishes of the family Cyprinidae. They are used in embryological studies and to study the effects of certain chemicals on development. [NIH] Zygote: The fertilized ovum. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]
635
INDEX A Abdomen, 549, 560, 590, 594, 607, 622, 623, 626, 630 Abdominal, 387, 545, 549, 550, 561, 566, 582, 605, 606, 629 Abdominal Pain, 387, 549, 582, 629 Abortion, 549, 612 Abscess, 549, 619 Absenteeism, 457, 549 Acantholysis, 549, 607 Acceptor, 549, 593, 605 Acculturation, 497, 549 Acetylcholine, 150, 152, 331, 341, 343, 362, 373, 386, 388, 452, 459, 462, 478, 480, 487, 502, 549, 564, 601, 602 Acidity, 549, 608 Acne, 549, 618 Acoustic, 343, 345, 350, 351, 353, 549, 631 Acquired Immunodeficiency Syndrome, 486, 549 Acrylonitrile, 424, 429, 549, 618 Actin, 549 Acuity, 466, 549 Adaptability, 550, 562 Adduct, 347, 550 Adenosine, 550, 561, 609 Adenylate Cyclase, 550, 581 Adhesives, 399, 424, 451, 549, 550, 560 Adipocytes, 550, 592 Adipose Tissue, 514, 550, 626 Adjustment, 395, 550 Adjuvant, 6, 7, 550 Adolescence, 363, 550 Adrenal Cortex, 550, 569, 578, 612 Adrenal Glands, 550, 553 Adrenal Medulla, 331, 472, 550, 562, 565, 577, 603, 606 Adrenergic, 342, 410, 550, 554, 574, 577, 608, 624, 629 Adrenolytic, 449, 550 Adverse Effect, 9, 348, 383, 498, 500, 536, 550, 592, 620 Aerobic, 425, 550 Aerosol, 361, 431, 441, 446, 473, 474, 475, 550, 603 Aetiology, 493, 550 Afferent, 550, 579, 592, 612 Affinity, 550, 551, 556, 621
Age of Onset, 551, 629 Ageing, 551 Agoraphobia, 551, 588, 606 Air Sacs, 551, 552 Airway, 152, 551, 596, 621 Akathisia, 551, 555 Aldehydes, 429, 430, 453, 551 Alertness, 388, 398, 551, 561 Algorithms, 551, 559 Alkaline, 425, 426, 427, 433, 447, 450, 551, 552, 561, 605 Alkaline Phosphatase, 551 Allergen, 551, 572, 619 Alloys, 551, 566 Alpha Particles, 551, 615 Alternative medicine, 513, 551 Alternative Splicing, 552, 613 Aluminum, 424, 552, 558 Alveoli, 472, 552, 615, 631 Amine, 552, 586 Amino Acid Sequence, 552, 554, 558 Amino Alcohols, 383, 552 Ammonia, 383, 441, 445, 552, 624, 630 Amnion, 552, 565 Amniotic Fluid, 552, 583, 596 Amphetamine, 341, 391, 552, 553, 558, 572 Amygdala, 335, 392, 552, 593 Amyloid, 552, 584 Amyloid beta-Protein, 552 Amyloidosis, 553 Anabasine, 390, 465, 553 Anaesthesia, 553, 589 Anal, 553, 580 Analeptic, 553, 623 Analgesic, 553, 599, 603, 604 Analog, 330, 488, 553, 581 Anatomical, 553, 556, 560, 564, 588, 597 Anemia, 553, 561, 566, 585 Anergy, 553 Anesthesia, 354, 551, 553, 601 Angina, 356, 515, 553, 603 Anginal, 553, 602 Angiogenesis, 418, 477, 553, 595 Anhydrous, 396, 461, 462, 469, 470, 553 Animal model, 352, 391, 498, 511, 553 Anions, 553, 591 Anomalies, 553, 625 Antagonism, 553, 561, 574
636 Nicotine
Antibacterial, 553, 591, 622 Antibiotic, 553, 598, 612, 622, 625 Antibodies, 390, 391, 466, 467, 554, 588, 594, 610 Antibody, 551, 554, 567, 586, 587, 588, 589, 591, 596, 599, 615, 616, 619, 633 Anticholinergic, 554, 563, 574, 609 Anticoagulant, 554, 613 Anticonvulsant, 554, 564, 566, 594 Antidepressant, 330, 376, 400, 554, 561, 569, 581, 588 Antiemetic, 554, 555, 564, 587 Antifungal, 554, 628 Antigen, 345, 551, 554, 567, 572, 586, 587, 588, 589, 596, 597, 619 Antigen-presenting cell, 554, 572 Antihistamine, 397, 554 Antihypertensive, 554, 581 Anti-infective, 554, 586 Antioxidant, 340, 554, 556, 605 Antipruritic, 554 Antipsychotic, 554, 564, 601, 618 Antispasmodic, 555, 604, 619 Anus, 553, 555, 560, 567, 616 Anxiety, 332, 370, 405, 408, 420, 421, 422, 456, 472, 481, 483, 504, 551, 555, 587, 592, 594, 603, 606, 612 Anxiolytic, 480, 555, 561, 564, 604 Aorta, 555, 631 Aortic Aneurysm, 450, 555, 582 Apathy, 555, 601 Aperture, 403, 555 Apolipoproteins, 555, 594 Apoptosis, 330, 555 Appetitive Behavior, 378, 555 Approximate, 555 Arachidonic Acid, 555, 575, 593, 613 Arecoline, 340, 354, 555 Arginine, 555, 602 Aromatic, 383, 391, 467, 555, 558, 608, 623 Arrhythmia, 515, 555 Arteries, 503, 512, 555, 559, 569, 594, 597, 599, 600, 626, 629 Arterioles, 555, 559, 600 Ascorbic Acid, 354, 476, 556, 587 Aseptic, 556, 622 Aspartic, 502, 556 Aspartic Acid, 556 Asphyxia, 556, 603 Assay, 341, 408, 409, 480, 556 Astringents, 556, 597 Astrocytes, 556, 597, 599
Astrocytoma, 556, 583 Asymptomatic, 556, 605 Atracurium, 556 Atrial, 556 Atrial Fibrillation, 556 Atrium, 556, 631 Atrophy, 478, 549, 556 Atropine, 348, 556, 557, 619 Attenuation, 331, 335, 556 Atypical, 481, 556, 603, 618 Auditory, 4, 352, 557, 578, 595, 612, 630 Autodigestion, 557, 606 Autonomic, 335, 344, 472, 478, 549, 555, 557, 558, 570, 582, 583, 602, 603, 607, 624 Autonomic Nervous System, 335, 557, 558, 570, 607, 624 Autoradiography, 336, 557 Aversion therapy, 486, 557 Avian, 353, 557 Axonal, 331, 335, 557 Axons, 557, 572, 604, 612, 615 B Bacteria, 553, 554, 557, 568, 597, 616, 622, 627, 628, 630 Bacterial toxin, 557 Bactericidal, 557, 578 Basal cells, 557, 625 Basal Ganglia, 555, 557, 565, 583, 587, 593, 603 Basement Membrane, 418, 557, 579, 592 Basophils, 557, 584, 592 Behavior Therapy, 366, 557 Belladonna, 556, 557 Benign, 426, 479, 558, 584, 600, 616, 632 Bentonite, 389, 558 Benzene, 558 Benzodiazepines, 455, 558, 561 Beta-Endorphin, 478, 558 Beta-pleated, 552, 558 Bile, 558, 582, 594, 596, 612, 622 Bile duct, 558, 612 Bile Pigments, 558, 596 Biliary, 558, 606 Biliary Tract, 558, 606 Binding Sites, 336, 342, 558 Bioavailability, 558 Biochemical reactions, 444, 445, 558 Biogenic Amines, 502, 558 Biological response modifier, 558, 590 Biomarkers, 525, 558 Biotechnology, 150, 494, 513, 523, 558 Biotransformation, 494, 559
Index 637
Biphasic, 559 Bipolar Disorder, 410, 559 Birth Certificates, 501, 559 Bladder, 455, 559, 564, 568, 589, 613, 630 Blastocyst, 559, 568, 575, 605, 609, 629 Blepharospasm, 559 Blinking, 410, 559 Blister, 559, 607 Blood Cell Count, 559, 585 Blood Coagulation, 559, 561, 626 Blood Glucose, 398, 504, 559, 585, 590 Blood Platelets, 559, 620 Blood vessel, 418, 463, 477, 504, 553, 559, 560, 562, 563, 564, 565, 569, 576, 584, 591, 594, 597, 607, 621, 623, 626, 630, 631 Blood-Brain Barrier, 151, 559, 593, 596, 609, 625 Body Fluids, 558, 559, 575, 610, 621, 629 Body Mass Index, 11, 559 Body Regions, 560, 566 Bombesin, 560 Bone Cements, 560, 611 Bone Density, 334, 560 Bone Marrow, 558, 560, 588, 594, 599, 621, 623 Bone scan, 560, 618 Boron, 560 Boron Neutron Capture Therapy, 560 Bowel, 387, 495, 553, 560, 573, 589, 590, 592, 623, 629 Bowel Movement, 560, 573, 623 Brachytherapy, 560, 590, 591, 615, 633 Bradykinesia, 560 Bradykinin, 560, 602, 610 Branch, 543, 560, 564, 575, 595, 606, 614, 621, 624, 625 Breakdown, 151, 560, 573, 582 Bromine, 436, 560 Bronchi, 561, 577, 628 Bronchial, 152, 561, 586 Bronchioles, 552, 561, 615 Bronchitis, 357, 455, 458, 472, 561, 565 Buccal, 354, 389, 395, 433, 443, 450, 475, 561, 623 Buccal mucosa, 354, 395, 561 Buspirone, 481, 561 C Cacao, 437, 561 Cadmium, 476, 561 Cadmium Poisoning, 561 Caesarean section, 500, 561
Calcium, 151, 342, 347, 349, 351, 470, 560, 561, 565, 567, 595, 602, 620 Calcium Carbonate, 470, 560, 561 Cannabis, 340, 341, 442, 561 Capsaicin, 431, 561 Capsules, 387, 390, 465, 495, 561, 574, 577, 580 Carbohydrate, 561, 583, 584, 611 Carbon Dioxide, 436, 562, 571, 580, 582, 609, 617, 630, 631 Carcinogen, 150, 152, 417, 463, 550, 562, 599 Carcinogenesis, 463, 562 Carcinogenic, 384, 402, 463, 476, 558, 562, 589, 603, 622 Carcinoma, 349, 562 Cardiac, 10, 330, 556, 561, 562, 577, 582, 599, 600, 622 Cardiac arrest, 562 Cardiorespiratory, 516, 562 Cardiovascular disease, 9, 388, 412, 420, 421, 422, 456, 457, 470, 488, 500, 515, 562 Cardiovascular System, 393, 562, 570 Catecholamine, 342, 498, 562, 574, 608 Catheter, 371, 374, 562 Cathode, 562 Cations, 386, 462, 562, 591 Caudal, 562, 573, 587, 603, 611 Caudate Nucleus, 562, 603 Cause of Death, 397, 398, 407, 420, 421, 422, 449, 456, 457, 483, 562 Cell Death, 555, 562 Cell Differentiation, 562, 620 Cell Division, 557, 562, 563, 596, 598, 609, 613 Cell membrane, 562, 572, 582, 609, 611 Cell proliferation, 330, 418, 563, 620 Cell Respiration, 563, 617 Cellobiose, 563 Cellulose, 400, 446, 447, 563, 609 Central Nervous System Infections, 563, 584 Centrifugation, 563, 585, 598, 625 Cerebral Cortex, 563, 578, 580, 615 Cerebral hemispheres, 557, 563, 583, 625 Cerebrovascular, 562, 563 Cerebrum, 563, 625 Cervical, 563 Cervix, 455, 549, 563 Cetirizine, 563, 587 Character, 446, 563, 571 Chemoreceptor, 555, 563
638 Nicotine
Chimeras, 331, 564 Chin, 349, 351, 371, 564, 596 Chlordiazepoxide, 481, 564 Chlorine, 403, 564, 587 Chlorophyll, 476, 564 Chlorpromazine, 564, 581 Chlorpyrifos, 564 Cholesterol, 357, 558, 564, 565, 569, 587, 593, 594, 596, 616, 618, 622 Cholesterol Esters, 564, 593 Choline, 341, 342, 564 Cholinergic Agonists, 478, 564, 602 Cholinesterase Inhibitors, 369, 564 Chondrocytes, 564, 580 Chorda Tympani Nerve, 564, 625 Chorea, 554, 565 Chorioamnionitis, 516, 565 Chorion, 565 Chromaffin Cells, 341, 565, 606 Chromans, 565 Chromatin, 555, 565, 577 Chromic, 565 Chromosome, 553, 565, 568, 584, 593, 629 Chronic Disease, 9, 534, 565 Chronic Obstructive Pulmonary Disease, 450, 500, 565 Chylomicrons, 565, 594 Circadian, 565 Circulatory system, 395, 565, 576 CIS, 330, 442, 530, 531, 565, 617 Cisplatin, 565, 604 Citric Acid, 402, 409, 437, 447, 565 Citrus, 556, 565 Clear cell carcinoma, 565, 572 Clinical Medicine, 566, 611 Clinical study, 566, 569 Clinical trial, 152, 365, 379, 523, 566, 569, 574, 609, 614, 616 Clonazepam, 410, 566 Clonic, 559, 566 Cloning, 151, 559, 566 Cobalt, 445, 566 Coca, 566 Cochlear, 566, 627, 631 Cochlear Diseases, 566, 627 Coenzyme, 556, 566 Cofactor, 566, 602, 613, 626 Cognition, 373, 483, 566, 601 Cognitive restructuring, 566, 623 Colchicine, 344, 566 Colic, 397, 566 Colitis, 4, 358, 387, 495, 566
Collagen, 550, 552, 557, 567, 579, 580, 595, 610, 613 Colloidal, 558, 567 Colon, 387, 392, 566, 567, 589, 592, 612, 620, 629 Combination Therapy, 567 Comorbidity, 496, 567 Complement, 567, 610, 619 Complementary and alternative medicine, 339, 359, 567 Complementary medicine, 339, 567 Complete remission, 568, 617 Compliance, 411, 568 Compulsions, 568, 603 Computational Biology, 523, 568 Computed tomography, 371, 373, 560, 568, 618 Computerized tomography, 568 Conception, 501, 549, 568, 580, 612, 622 Concomitant, 4, 568 Conduction, 568, 626 Confounding, 568 Congestion, 555, 568, 577 Conjugated, 390, 466, 568, 570, 584 Conjugation, 559, 568 Conjunctiva, 568, 609, 628 Connective Tissue, 556, 560, 567, 568, 572, 582, 594, 597, 607, 618, 623 Consciousness, 553, 569, 571, 574, 614 Constipation, 555, 569 Contact dermatitis, 4, 569 Continuous infusion, 336, 341, 498, 569 Contraindications, ii, 569 Control group, 4, 5, 7, 8, 346, 569, 609 Controlled clinical trial, 569 Controlled study, 3, 569 Coordination, 487, 569 Corneum, 569, 577 Coronary Arteriosclerosis, 569, 600 Coronary heart disease, 10, 388, 417, 432, 443, 562, 569 Coronary Thrombosis, 569, 597, 599, 600 Corpus, 569, 612, 626, 632 Corpus Luteum, 569, 612 Cortex, 478, 569, 577, 578, 612, 616 Cortical, 335, 569, 578, 612, 615, 619 Corticosteroids, 387, 569 Cortisol, 478, 569 Coumarin, 570 Courtship, 555, 570 Crack Cocaine, 570
Index 639
Cranial, 564, 570, 579, 583, 584, 591, 607, 628, 630, 631 Craniocerebral Trauma, 570, 584, 627 Cruciferous vegetables, 570, 608 Cues, 372, 405, 406, 570 Curative, 570, 602 Cutaneous, 392, 454, 569, 570, 591, 606 Cyanide, 570, 611 Cyanogen Bromide, 399, 409, 570 Cyanosis, 570, 596 Cyclic, 335, 452, 550, 561, 570, 581, 584, 602, 613 Cytochrome, 150, 463, 570 Cytokine, 570 Cytoplasm, 555, 557, 562, 570, 571, 576, 577, 625 Cytoskeleton, 333, 571 Cytotoxic, 561, 571, 604, 616, 620 Cytotoxic chemotherapy, 571, 604 Cytotoxicity, 334, 347, 354, 565, 571 D Data Collection, 571, 581 De novo, 418, 571 Deamination, 571, 599, 630 Decarboxylation, 558, 571, 586 Decidua, 571, 609 Decision Making, 8, 571 Defense Mechanisms, 571 Degenerative, 483, 571, 599 Deletion, 555, 571 Delirium, 554, 571 Delivery of Health Care, 571, 585 Delusions, 571, 614 Dementia, 373, 483, 549, 554, 571 Dendrites, 571, 572, 601, 615 Dendritic, 572, 622 Dendritic cell, 572 Density, 342, 403, 560, 563, 572, 594, 604, 610 Dental Amalgam, 572 Dentate Gyrus, 330, 572, 586 Depolarization, 386, 462, 572, 620 Depressive Disorder, 572, 594 Deprivation, 332, 344, 351, 372, 420, 421, 422, 457, 572 Dermal, 389, 429, 454, 572 Dermatitis, 572, 575, 587 Dermis, 572, 624, 628 DES, 332, 572 Desensitization, 572 Detoxification, 572 Deuterium, 572, 586
Developed Countries, 398, 450, 572 Developing Countries, 485, 572 Dextroamphetamine, 552, 572, 597 Diabetes Mellitus, 503, 573, 583, 585 Diabetic Retinopathy, 418, 477, 573 Diagnostic procedure, 381, 513, 573 Diarrhea, 387, 573 Diastole, 573, 612 Diastolic, 573, 587 Diencephalon, 573, 587, 612, 625, 626 Dietary Fats, 517, 573 Digestion, 558, 560, 573, 590, 594, 623 Digestive system, 379, 573 Dilatation, 549, 573, 615 Dilator, 573, 603 Dilution, 396, 446, 471, 573 Diploid, 573, 609, 629 Direct, iii, 9, 409, 413, 426, 427, 431, 433, 442, 443, 472, 500, 502, 566, 573, 574, 587, 608, 616, 624 Discrete, 399, 400, 573 Discrimination, 332, 573 Disinfectant, 573, 578 Dispenser, 414, 460, 573 Dissection, 573 Dissociation, 550, 573, 591 Distal, 557, 574, 607, 612, 614, 615 Diuresis, 561, 574 Dizziness, 402, 574, 606 Dopa, 574, 593 Dosage Forms, 467, 482, 574 Dose-dependent, 499, 574 Double-blind, 8, 12, 574 Doxepin, 481, 574 Drinking Behavior, 574 Drive, ii, vii, 329, 468, 525, 533, 574, 593 Drug Delivery Systems, 387, 574 Drug Tolerance, 574, 627 Duct, 575, 618, 622, 624 Duodenum, 558, 575, 582, 592, 623 Dyes, 552, 557, 575, 602, 624 Dyskinesia, 410, 411, 555, 575 Dysphoric, 572, 575 Dystonia, 555, 575 Dystrophic, 333, 575 E Eczema, 340, 513, 575 Edema, 569, 573, 575, 591, 599, 603, 630 Effector, 549, 567, 575, 601 Eicosanoids, 575 Ejaculation, 575, 619 Elasticity, 413, 569, 575
640 Nicotine
Elastin, 567, 575, 579 Elective, 500, 531, 575 Electrocardiogram, 372, 374, 575 Electrolysis, 553, 562, 575 Electrolyte, 571, 575, 611, 621, 630 Electrophysiological, 344, 345, 369, 489, 575 Electroplating, 575, 624 Emaciation, 549, 575 Embryo, 387, 499, 549, 552, 559, 562, 575, 580, 589, 597, 612, 622, 630 Embryo Transfer, 575, 612 Embryology, 576, 580 Emollient, 576, 583, 604 Emphysema, 385, 455, 458, 465, 469, 472, 565, 576 Empirical, 416, 576 Emulsion, 557, 576, 580 Endocrine System, 576, 601 Endogenous, 502, 558, 560, 574, 575, 576 Endometrium, 571, 576, 596, 629 Endorphins, 576, 602 Endoscopy, 4, 576 Endothelial cell, 333, 418, 502, 559, 576, 580, 626 Endothelium, 576, 602, 610 Endothelium, Lymphatic, 576 Endothelium, Vascular, 576 Endothelium-derived, 576, 602 Endotoxins, 567, 576, 592 Energy balance, 577, 592 Enhancers, 432, 577 Enkephalin, 502, 558, 577 Enteric-coated, 387, 577 Enteritis, 577 Entorhinal Cortex, 577, 586 Environmental Health, 365, 522, 524, 533, 577 Environmental tobacco smoke, 577 Enzymatic, 552, 558, 561, 567, 577, 586, 596, 617 Eosinophils, 577, 584, 592 Epidemiological, 495, 498, 577 Epidermal, 577, 592, 632 Epidermis, 389, 549, 557, 559, 569, 572, 577, 586, 592, 607, 612 Epidermoid carcinoma, 577, 622 Epinephrine, 550, 558, 565, 574, 577, 602, 603, 629 Epithelial, 151, 152, 571, 577, 592 Epithelial Cells, 151, 152, 577, 592 Epithelium, 557, 576, 577, 582, 606
Erectile, 503, 577 Erection, 503, 577 ERV, 577, 579 Erythema, 569, 577, 630 Erythrocyte Indices, 559, 578 Erythrocytes, 553, 559, 560, 578, 619 Esophageal, 455, 578 Esophagus, 394, 468, 573, 578, 585, 594, 608, 623 Estradiol, 432, 443, 578 Estrogen, 374, 482, 483, 578, 616, 619 Estrogen receptor, 482, 578 Ethanol, 341, 345, 364, 499, 578, 579 Ethnic Groups, 483, 578 Eukaryotic Cells, 578, 589 Euphoria, 392, 578 Evacuation, 569, 578, 582, 592 Evoke, 578, 623 Evoked Potentials, 344, 578 Excipient, 418, 419, 578 Excitation, 563, 578, 602 Excitatory, 330, 578, 583 Exogenous, 559, 575, 576, 578, 629 Expiration, 578, 579, 617 Expiratory, 577, 578, 579 Expiratory Reserve Volume, 577, 579 External-beam radiation, 579, 591, 615, 633 Extracellular, 343, 347, 552, 556, 568, 569, 579, 580, 595, 621 Extracellular Matrix, 568, 569, 579, 580, 595 Extracellular Matrix Proteins, 579, 595 Extracellular Space, 579 Extraction, 425, 427, 436, 437, 441, 462, 579 Extrapyramidal, 551, 555, 574, 579 Eye Movements, 363, 371, 579 F Facial, 410, 564, 579, 595, 625 Facial Nerve, 579, 625 Family Planning, 523, 579 Family Practice, 12, 579 Family Relations, 486, 579 Fat, 516, 517, 550, 555, 560, 569, 579, 592, 593, 618, 621, 629 Fatigue, 387, 579 Fatty acids, 449, 474, 475, 478, 575, 579, 584, 596, 613, 626 Fermentation, 561, 579 Fertilization in Vitro, 579, 612 Fertilizers, 580, 602, 624 Fetal Blood, 502, 565, 580, 609
Index 641
Fetal Death, 499, 580 Fetal Development, 499, 580 Fetal Growth Retardation, 500, 502, 580 Fetal Heart, 516, 580 Fetus, 487, 498, 499, 502, 515, 516, 549, 565, 580, 596, 609, 612, 622, 629, 630 Fibrinogen, 580, 610, 626 Fibroblast Growth Factor, 580 Fibroblasts, 340, 354, 580 Filler, 402, 427, 439, 446, 464, 580 Filtration, 447, 580 Fissure, 564, 572, 580, 612 Fixation, 580, 619 Flatus, 581, 582 Flavoring Agents, 474, 581 Flicker Fusion, 3, 581 Flunitrazepam, 581 Fluorouracil, 581, 593 Fluoxetine, 355, 397, 410, 481, 581 Fluphenazine, 410, 581 Flushing, 581 Focus Groups, 11, 581 Follicular Fluid, 581 Foramen, 564, 581, 595 Forearm, 559, 581 Fornix, 341, 581 Forskolin, 581 Fractionation, 581, 625 Free Radicals, 554, 573, 581 Frontal Lobe, 581, 612 Frostbite, 581, 608 Functional magnetic resonance imaging, 370, 392, 581 Fungi, 554, 568, 581, 597, 633 G GABA, 335, 469, 482, 483, 566, 582, 620 Galanthamine, 434, 582 Gallbladder, 549, 558, 573, 582 Ganglia, 472, 549, 582, 601, 602, 606, 607, 624 Ganglionic Blockers, 582, 596 Gap Junctions, 582, 625 Gas, 401, 409, 426, 458, 552, 562, 564, 577, 581, 582, 586, 599, 602, 603, 604, 610, 624, 631 Gas exchange, 582, 631 Gastric, 547, 557, 560, 574, 582, 585, 586 Gastric Emptying, 582 Gastric Mucosa, 582 Gastrin, 582, 586 Gastroenteritis, 560, 582
Gastrointestinal tract, 4, 488, 564, 578, 582, 593, 596, 620, 629 Gels, 473, 474, 582 Gene Expression, 349, 583 Genetics, 486, 568, 583 Genital, 565, 583, 630 Genitourinary, 583, 630 Genotype, 583, 608 Germ Cells, 583, 596, 604, 605, 625 Gestation, 498, 499, 583, 607, 609, 622 Gestational, 580, 583, 596 Gestational Age, 583, 596 Gingivitis, 428, 583 Ginseng, 343, 346, 348, 349, 359, 481, 583 Gland, 550, 583, 594, 605, 609, 613, 616, 619, 623, 624, 626 Glioblastoma, 583 Glioma, 583 Glossopharyngeal Nerve, 583, 625 Glucose, 398, 504, 556, 559, 563, 573, 583, 585, 590 Glucose Intolerance, 573, 583 Glutamate, 478, 583 Glutamic Acid, 437, 583, 602, 613 Glycerol, 400, 583, 584, 609 Glycerophospholipids, 584, 609 Glycine, 552, 584, 602, 623 Glycoproteins, 584, 591, 596, 611, 614 Gout, 533, 566, 584 Governing Board, 584, 611 Grade, 9, 11, 412, 516, 524, 584 Graft, 584, 586, 588 Granule, 572, 584 Granulocyte, 584 Granulosa Cells, 584 Guanylate Cyclase, 584, 602 H Habitual, 352, 383, 384, 393, 402, 415, 416, 514, 563, 584 Haematoma, 393, 584 Hair follicles, 572, 584, 632 Half-Life, 432, 443, 584 Haploid, 584, 609 Headache, 402, 546, 561, 584 Headache Disorders, 584 Health Care Costs, 369, 585 Health Education, 11, 336, 585 Health Expenditures, 585 Health Promotion, 485, 534, 585 Health Services, 336, 367, 369, 404, 571, 585 Hearing aid, 514, 585
642 Nicotine
Heart attack, 388, 562, 585 Heartbeat, 546, 585 Heartburn, 433, 435, 443, 585 Hematocrit, 559, 578, 585 Hematopoiesis, 585 Heme, 570, 585, 611 Hemodialysis, 561, 585 Hemodynamics, 585 Hemoglobin, 458, 553, 559, 570, 578, 585, 592 Hemorrhage, 516, 570, 584, 585, 623, 632 Hemostasis, 585, 620 Hepatic, 347, 455, 571, 586, 599 Hereditary, 584, 586, 599 Heredity, 582, 583, 586 Hippocampus, 478, 572, 581, 586, 593, 615, 623 Histamine, 342, 554, 558, 563, 574, 586, 587 Histidine, 586 Homicide, 586 Homogeneous, 416, 586, 608 Homologous, 586, 619, 624 Hormonal, 556, 565, 586, 607 Hormone, 558, 569, 572, 575, 577, 578, 582, 586, 590, 592, 612, 618, 620, 626 Horny layer, 577, 586 Host, 152, 452, 472, 586, 588, 593, 630, 632 Human papillomavirus, 586 Hydrobromic Acid, 436, 586 Hydrochloric Acid, 436, 586 Hydrogen, 436, 440, 449, 549, 552, 557, 561, 572, 579, 586, 587, 593, 598, 602, 605, 608, 614 Hydrogen Cyanide, 440, 586 Hydrogen Peroxide, 436, 586, 593 Hydrogenation, 558, 586 Hydrolysis, 556, 559, 563, 565, 587, 593, 609 Hydrophobic, 584, 587, 593 Hydroxylation, 150, 587, 629 Hydroxylysine, 567, 587 Hydroxyproline, 552, 567, 587 Hydroxyzine, 481, 587 Hypercholesterolemia, 515, 587 Hyperglycemia, 348, 587 Hypericum, 347, 435, 470, 587 Hypersensitivity, 410, 551, 572, 587, 593, 618, 619 Hypersensitivity, Immediate, 587 Hypertension, 338, 342, 357, 397, 515, 562, 587, 591, 596, 608, 630 Hypnotic, 587, 594
Hypochlorous Acid, 587 Hypokinesia, 587, 606 Hypoplasia, 587 Hypotension, 555, 582, 587 Hypothalamic, 587 Hypothalamus, 557, 573, 577, 587, 593, 609, 626 Hypoxemia, 498, 587 Hypoxia, 502, 571, 587 Hypoxic, 498, 588 I Id, 337, 356, 530, 531, 534, 536, 542, 544, 588 Idiopathic, 387, 588, 615 Ileum, 387, 392, 588, 592 Imipramine, 481, 588 Immune function, 588 Immune response, 345, 550, 553, 554, 588, 619, 624, 630, 632 Immune Sera, 588 Immune system, 554, 588, 593, 594, 595, 600, 630, 632 Immunity, 549, 588, 628 Immunization, 390, 466, 588, 619 Immunodeficiency, 549, 588 Immunogen, 588 Immunogenic, 390, 466, 588 Immunologic, 583, 588, 616 Immunology, 331, 550, 551, 588 Immunosuppressive, 588 Immunotherapy, 572, 588 Impairment, 442, 483, 487, 571, 575, 588, 597, 614 Implant radiation, 588, 590, 591, 615, 633 Implantation, 568, 588, 605 Impotence, 503, 577, 588, 608 Impregnation, 403, 437, 588 In situ, 336, 412, 448, 588 In Situ Hybridization, 336, 589 In vivo, 345, 347, 390, 398, 432, 443, 466, 589, 626 Incidental, 589 Incision, 500, 561, 589, 591 Incontinence, 589, 619 Indicative, 488, 589, 606, 630 Induction, 418, 455, 477, 554, 582, 589, 615 Infancy, 516, 589 Infant Mortality, 516, 589 Infarction, 589 Infection, 549, 556, 557, 558, 571, 582, 584, 588, 589, 594, 601, 604, 618, 623, 630, 632
Index 643
Inflammation, 387, 418, 477, 549, 561, 565, 566, 569, 572, 577, 582, 583, 589, 591, 593, 603, 605, 607, 610, 612, 617, 618, 623, 629, 630, 632 Inflammatory bowel disease, 4, 387, 495, 589 Infusion, 343, 589 Ingestion, 413, 462, 464, 561, 589, 610 Inhalation, 9, 385, 393, 409, 431, 448, 467, 472, 473, 474, 475, 550, 589, 610 Initiation, 589 In-line, 399, 451, 589 Innervation, 574, 579, 589 Inorganic, 565, 590, 595, 599, 603 Inotropic, 352, 574, 590 Inpatients, 590 Insecticides, 590, 608, 632 Insomnia, 357, 590, 594 Insulin, 357, 514, 590, 629 Insulin-dependent diabetes mellitus, 590 Intensive Care, 590 Interferon, 590 Interferon-alpha, 590 Interindividual, 590 Interleukin-1, 590 Interleukin-2, 590 Intermittent, 152, 353, 357, 581, 590 Internal radiation, 590, 591, 615, 633 Interstitial, 560, 579, 590, 591, 633 Intestinal, 387, 392, 590, 596 Intestine, 392, 560, 577, 590, 592 Intoxication, 571, 590, 632 Intracellular, 151, 561, 589, 591, 596, 602, 611, 613, 616, 620 Intracranial Hypertension, 584, 591, 627 Intraocular, 581, 591 Intraocular pressure, 581, 591 Intravenous, 335, 376, 408, 431, 448, 473, 589, 591 Intrinsic, 551, 557, 591 Invasive, 588, 591, 595 Invertebrates, 452, 591 Involuntary, 411, 559, 565, 577, 591, 600, 617, 620, 621, 627 Ion Channels, 386, 462, 556, 591, 625 Ion Exchange, 396, 428, 461, 462, 469, 470, 563, 591 Ion Exchange Resins, 396, 469, 470, 591 Ionization, 591 Ions, 398, 445, 549, 557, 573, 575, 586, 591, 598, 611 Irradiation, 560, 591, 633
Irritants, 392, 431, 514, 516, 591 Ischemia, 556, 591 Isoniazid, 409, 591 J Jejunum, 342, 592 Joint, 387, 592, 624 K Kava, 470, 592 Kb, 522, 592 Keratin, 592 Keratinocytes, 592 Keto, 463, 592 Kinetic, 592 L Lactation, 592 Laminin, 557, 579, 592 Large Intestine, 573, 590, 592, 616, 621 Larynx, 394, 455, 468, 592, 628, 630 Latent, 350, 592, 612 Lavage, 547, 592 Laxative, 592, 595 Leptin, 335, 592 Leucine, 558, 592 Leukocytes, 557, 559, 560, 577, 590, 592 Leukotrienes, 555, 575, 593 Levamisole, 593 Levodopa, 370, 574, 593 Libido, 352, 593 Library Services, 542, 593 Life cycle, 559, 582, 593 Life Expectancy, 593 Ligaments, 569, 593 Ligands, 349, 459, 478, 593 Limbic, 552, 593, 612 Limbic System, 552, 593, 612 Linkage, 487, 563, 593 Lip, 426, 593 Lipid, 340, 454, 555, 564, 583, 590, 592, 593, 605, 629 Lipid Peroxidation, 340, 593, 605 Lipolysis, 478, 593 Lipopolysaccharide, 593 Lipoprotein, 10, 593, 594 Lithium, 554, 594 Liver scan, 594, 618 Lobe, 353, 594 Lobeline, 343, 383, 406, 442, 594 Local Government, 486, 487, 594 Localized, 553, 580, 584, 589, 592, 594, 599, 609, 630 Locomotion, 594, 609 Locomotor, 333, 351, 594
644 Nicotine
Long-Term Potentiation, 594 Lorazepam, 594 Low-density lipoprotein, 594 Lower Esophageal Sphincter, 594 Lubricants, 447, 594 Lymph, 563, 565, 576, 594 Lymph node, 563, 594 Lymphatic, 576, 589, 594, 597, 621, 622, 626 Lymphocyte, 549, 554, 594, 595, 596 Lymphocyte Count, 549, 595 Lymphoid, 554, 569, 595 Lysine, 362, 502, 587, 595 M Macrophage, 590, 595 Magnesium Hydroxide, 595 Magnesium Oxide, 470, 595 Magnetic Resonance Imaging, 372, 595, 618 Maintenance therapy, 408, 472, 495, 595 Malformation, 499, 595 Malignant, 549, 583, 595, 600, 616 Malnutrition, 556, 595 Mandible, 564, 595 Manic, 554, 559, 594, 595, 614 Manic-depressive psychosis, 595, 614 Manifest, 557, 595 Marital Status, 9, 595 Mastication, 595, 628 Matrix metalloproteinase, 595 Meat, 573, 595 Meat Products, 573, 595 Meatus, 595, 630 Mecamylamine, 343, 348, 368, 373, 408, 409, 410, 472, 596 Meconium, 516, 596 Meconium Aspiration, 516, 596 Medial, 341, 596 Mediate, 335, 459, 498, 574, 596 Mediator, 574, 590, 596, 620 Medicament, 394, 452, 466, 468, 472, 596 MEDLINE, 523, 596 Meiosis, 596, 624 Melanin, 596, 608, 629 Membrane Glycoproteins, 596 Membrane Lipids, 596, 609 Meninges, 563, 570, 596 Menopause, 596, 611 Menstrual Cycle, 596, 612 Menstruation, 571, 596, 612 Mental Disorders, 380, 405, 487, 587, 596, 614
Mental Health, v, 333, 367, 371, 380, 410, 522, 526, 597, 614 Mental Processes, 573, 597, 614 Menthol, 423, 597 Mercury, 436, 476, 572, 597 Mesenchymal, 418, 597 Mesoderm, 597, 629 Mesolimbic, 350, 555, 597, 631 Meta-Analysis, 597 Metabolite, 334, 408, 409, 510, 559, 587, 597, 603 Metabolization, 443, 597 Metastasis, 595, 597 Methionine, 502, 558, 597, 624 Methylphenidate, 597 MI, 11, 397, 477, 547, 597 Microbe, 597, 627 Microbiology, 556, 597 Microglia, 556, 597, 599 Microorganism, 438, 439, 440, 454, 566, 597, 632 Microscopy, 557, 598 Microsomal, 455, 598 Microspheres, 388, 389, 407, 598 Microwaves, 598, 615 Migration, 418, 598 Milligram, 8, 393, 426, 479, 485, 598 Milliliter, 560, 598 Minocycline, 598 Minority Groups, 486, 496, 598 Miscarriage, 500, 598 Miscible, 417, 598, 608 Mitosis, 555, 598 Mobilization, 151, 598 Modification, 400, 417, 552, 598 Modulator, 482, 598 Molecular Structure, 598, 628 Molecule, 554, 557, 558, 566, 567, 570, 573, 575, 576, 578, 587, 598, 605, 616, 620 Monitor, 371, 405, 598, 603 Monoamine, 481, 552, 572, 599, 629 Monoamine Oxidase, 481, 552, 572, 599, 629 Monoclonal, 591, 599, 615, 633 Monocyte, 599 Mononuclear, 599 Mood Disorders, 459, 599 Morphine, 332, 341, 485, 502, 599, 600, 604 Morphological, 331, 499, 551, 575, 599 Motility, 599, 620 Motion Sickness, 599, 600, 619 Mouth Ulcer, 433, 435, 443, 599
Index 645
Movement Disorders, 410, 487, 554, 599 Mucilaginous, 596, 599 Mucins, 584, 599, 618 Mucosa, 415, 423, 435, 477, 582, 599, 600, 623 Mucus, 599, 629 Mustard Gas, 591, 599 Mutagen, 599 Mutagenic, 599, 603 Mydriatic, 599, 619 Myelogenous, 599 Myocardial infarction, 450, 515, 569, 597, 599, 600 Myocardial Ischemia, 351, 599 Myocardium, 597, 599, 600 Myometrium, 500, 600 Myristate, 600 N Naive, 420, 421, 422, 456, 600 Naloxone, 410, 558, 600 Naltrexone, 366, 372, 375, 600 Narcolepsy, 572, 597, 600 Narcosis, 600 Narcotic, 599, 600, 603 Nasal Cavity, 600 Nasal Mucosa, 345, 395, 406, 407, 423, 477, 600 Nausea, 4, 413, 435, 443, 554, 574, 582, 600, 604, 606, 630 NCI, 1, 374, 379, 521, 525, 530, 531, 565, 600 Neonatal, 344, 345, 348, 498, 589, 600 Neoplasm, 600, 629 Nerve, 503, 550, 553, 557, 564, 571, 579, 583, 589, 596, 599, 600, 601, 604, 606, 607, 611, 617, 623, 625, 628, 630, 631 Nerve Endings, 600, 625 Nerve Growth Factor, 601 Neural, 391, 478, 550, 552, 553, 582, 597, 599, 601, 607 Neuroblastoma, 362, 601 Neuroeffector Junction, 600, 601, 602 Neuroendocrine, 361, 601 Neurofilaments, 331, 601 Neuroleptic, 410, 551, 554, 601, 604 Neurologic, 583, 601 Neuromuscular, 549, 556, 601, 602, 626, 629, 630 Neuromuscular Blocking Agents, 556, 601 Neuromuscular Junction, 549, 601, 602 Neurons, 351, 478, 483, 566, 572, 578, 582, 593, 600, 601, 602, 615, 624, 631
Neuropathy, 601, 607 Neuropeptide, 601 Neurophysiology, 572, 601 Neuropsychological Tests, 371, 601 Neurotic, 601, 630 Neurotoxicity, 345, 602 Neutrons, 551, 560, 591, 602, 615 Neutrophil, 602 Niacin, 337, 338, 409, 602, 629 Nickel, 476, 602 Nicotinic Agonists, 383, 602 Nicotinic Antagonists, 383, 602 Nifedipine, 354, 602 Nitric acid, 437, 602 Nitric Oxide, 336, 602 Nitrogen, 365, 436, 440, 445, 551, 552, 579, 580, 586, 602, 603, 629 Nitrogen Dioxide, 365, 603 Nitrogen Oxides, 440, 445, 603 Nitroglycerin, 432, 443, 603 Nitrosamines, 463, 488, 603 Nitrous Oxide, 503, 603 Norepinephrine, 331, 343, 344, 459, 478, 550, 574, 602, 603, 608 Normotensive, 603 Nortriptyline, 376, 603 Nuclear, 373, 557, 566, 568, 578, 579, 583, 593, 603, 615, 626 Nuclear Family, 579, 603 Nuclear Medicine, 373, 603 Nuclei, 551, 552, 568, 593, 595, 598, 602, 603, 610, 614, 631 Nucleic acid, 589, 603 Nucleus Accumbens, 392, 478, 603, 631 O Obsessive-Compulsive Disorder, 410, 603 Oculi, 559, 604 Odds Ratio, 604, 617 Odour, 555, 604, 630 Office Visits, 506, 604 Ointments, 574, 604 Olfaction, 604 Oncology, 419, 604 Ondansetron, 377, 604 Oocytes, 604 Opacity, 572, 604 Opiate, 404, 493, 558, 577, 599, 600, 604 Opium, 599, 604 Opportunistic Infections, 549, 604 Optic Disk, 573, 604 Orbicularis, 559, 604 Orbit, 604
646 Nicotine
Orbital, 334, 604 Orthostatic, 555, 604 Osmosis, 604 Osmotic, 433, 604 Outpatient, 366, 368, 369, 496, 605 Ovarian Follicle, 569, 581, 584, 605 Ovaries, 605, 620, 626 Ovary, 569, 578, 605, 623 Overdose, 448, 545, 605 Ovulation, 584, 605 Ovum, 569, 571, 581, 583, 593, 605, 612, 629, 632, 633 Ovum Implantation, 605, 629 Oxidation, 343, 395, 416, 442, 452, 549, 554, 559, 570, 593, 605, 626 Oxidation-Reduction, 559, 605 Oxidative Stress, 331, 605 Oxides, 603, 605 Oxygen Consumption, 605, 617 Oxygenation, 587, 605 P Palate, 583, 605, 621, 623, 625, 630 Pancreas, 549, 558, 573, 590, 605, 629 Pancreatic, 358, 455, 605, 606 Pancreatitis, 4, 605 Panic, 588, 606 Panic Disorder, 588, 606 Papillomavirus, 606 Paraganglia, Chromaffin, 565, 606 Paralysis, 606, 626 Parasympathomimetic, 555, 606 Paresthesia, 606, 626 Parkinsonism, 332, 555, 593, 606 Paroxetine, 481, 606 Partial remission, 606, 617 Pathogenesis, 152, 410, 606 Pathologic, 418, 477, 555, 569, 587, 606, 614 Pathologic Processes, 555, 606 Pathologies, 386, 462, 478, 606 Pathophysiology, 487, 606 Patient Compliance, 433, 455, 606 Patient Education, 503, 535, 540, 542, 547, 607 Pelvis, 549, 605, 607, 630 Pemphigus, 549, 607 Peptide, 459, 552, 558, 580, 592, 607, 613 Perception, 4, 607, 619 Perennial, 587, 607, 628 Perforation, 555, 581, 607 Perfusion, 587, 607 Perinatal, 9, 515, 589, 607 Periodicity, 607, 618
Periodontal disease, 607 Periodontal Ligament, 334, 340, 607 Periodontitis, 583, 607 Peripheral blood, 590, 607 Peripheral Nervous System, 602, 607, 612, 623 Peripheral Neuropathy, 504, 607 Peripheral Vascular Disease, 358, 450, 607, 608 Peripheral vision, 608, 609 Peroxide, 436, 608 Pest Control, 384, 608 Pesticides, 590, 608 PH, 151, 343, 371, 373, 560, 608 Pharmaceutical Preparations, 563, 578, 608 Pharmaceutical Solutions, 574, 608 Pharmacodynamics, 487, 608 Pharmacokinetic, 488, 608 Pharmacotherapy, 10, 352, 410, 515, 608 Pharynx, 600, 608, 625, 630 Phenethyl isothiocyanate, 332, 608 Phenotype, 152, 608 Phentolamine, 501, 608 Phenylalanine, 470, 608, 629 Phenylpropanolamine, 376, 608 Phorbol, 608 Phospholipases, 362, 609, 620 Phospholipids, 579, 593, 596, 609 Phosphorus, 561, 609 Phosphorylation, 609 Physical Examination, 7, 583, 609 Physiologic, 551, 574, 580, 584, 587, 596, 609, 613, 616, 620, 628 Physostigmine, 388, 609 Pigments, 558, 566, 609, 617 Pilot study, 609 Piper methysticum, 592, 609 Pituitary Gland, 580, 581, 609 Placebos, 375, 609 Placenta, 499, 502, 516, 578, 580, 609, 612, 629, 630 Placental tissue, 502, 609 Plaque, 553, 609 Plasma cells, 554, 610 Plasma protein, 576, 581, 610 Plasmin, 610 Plasminogen, 610 Plasminogen Activators, 610 Plasticizers, 447, 610 Platelet Activation, 610, 620 Platelet Aggregation, 581, 602, 610, 626
Index 647
Platelets, 393, 602, 610, 626 Pleomorphic, 603, 610 Pneumonia, 569, 610 Pneumothorax, 596, 610 Poisoning, 340, 513, 561, 571, 582, 590, 597, 600, 610 Polyethylene, 384, 401, 414, 417, 610 Polymers, 389, 416, 591, 610, 613, 623 Polymorphic, 564, 572, 611 Polymorphism, 611 Polysaccharide, 407, 554, 563, 611, 614 Porosity, 396, 611 Port, 461, 464, 611 Port-a-cath, 611 Posterior, 553, 583, 604, 605, 611, 630 Postmenopausal, 378, 611, 616 Postnatal, 515, 611 Postoperative, 505, 611 Postsynaptic, 601, 611, 620, 625 Post-synaptic, 459, 611, 625 Post-traumatic, 584, 599, 611 Potassium, 344, 371, 374, 398, 403, 409, 459, 476, 611 Potassium Channels, 611 Potassium Cyanide, 409, 611 Potentiate, 500, 611 Potentiation, 348, 564, 594, 611, 620 Practicability, 611, 628 Practice Guidelines, 526, 611 Precursor, 150, 474, 555, 564, 574, 575, 576, 577, 593, 603, 608, 610, 611, 629 Predisposition, 612 Prefrontal Cortex, 612 Pregnancy Complications, 516, 612 Pregnancy Outcome, 372, 501, 612 Preload, 612 Premedication, 612, 619 Premenstrual, 612 Prenatal, 352, 487, 500, 501, 575, 612 Presynaptic, 386, 459, 462, 574, 601, 602, 612, 625 Presynaptic Terminals, 386, 462, 574, 601, 612, 625 Prevalence, 5, 9, 367, 369, 390, 450, 465, 497, 500, 534, 604, 612 Prickle, 549, 592, 612 Primary Sclerosing Cholangitis, 612 Private Sector, 487, 612 Proctocolitis, 387, 612 Proctosigmoiditis, 612 Progesterone, 612, 622 Progression, 553, 612
Progressive, 483, 562, 571, 574, 584, 610, 612, 629 Projection, 571, 603, 612, 613, 615, 616, 631 Proline, 567, 587, 613 Prone, 431, 613 Prophase, 604, 613, 624 Prophylaxis, 612, 613, 618, 630 Prostaglandin, 613, 626 Prostaglandins A, 613 Prostate, 532, 558, 613, 629 Protease, 418, 567, 613 Protein C, 552, 555, 592, 593, 613, 630 Protein Isoforms, 552, 613 Protein S, 494, 553, 559, 613, 626 Proteoglycans, 557, 579, 614 Protocol, 6, 366, 367, 373, 496, 609, 614 Protons, 551, 586, 614, 615 Protozoa, 568, 597, 614 Proximal, 574, 600, 612, 614, 619 Pruritic, 575, 614 Pruritus, 587, 614, 630 Psoriasis, 599, 614, 618 Psychic, 593, 596, 614, 619 Psychoactive, 391, 397, 398, 407, 467, 485, 492, 493, 614, 632 Psychomotor, 571, 601, 614 Psychosis, 459, 554, 583, 614 Psychotomimetic, 552, 573, 614 Public Policy, 523, 614 Pulmonary, 9, 389, 455, 458, 475, 559, 564, 569, 593, 615, 631 Pulmonary Artery, 559, 615, 631 Pulmonary Edema, 564, 615 Pulmonary Emphysema, 455, 615 Pulse, 407, 426, 451, 466, 479, 598, 615 Purulent, 549, 615 Pyoderma, 615 Pyoderma Gangrenosum, 615 Pyramidal Cells, 572, 615 Q Quaternary, 615, 619 Quinpirole, 615 R Race, 574, 598, 615 Radiation, 374, 392, 557, 579, 581, 590, 591, 615, 616, 618, 633 Radiation therapy, 579, 581, 590, 591, 615, 633 Radio Waves, 370, 372, 373, 598, 615 Radioactive, 371, 374, 557, 560, 584, 586, 588, 590, 591, 594, 603, 615, 616, 618, 633 Radioactivity, 371, 615
648 Nicotine
Radioisotope, 616, 628 Radiolabeled, 591, 615, 616, 633 Radiology, 603, 616 Radiotherapy, 560, 591, 615, 616, 633 Rage, 410, 616 Raloxifene, 616, 619 Reaction Time, 3, 616 Reactive Oxygen Species, 616 Reagent, 409, 564, 570, 586, 616 Reality Testing, 614, 616 Receptors, Muscarinic, 478, 616 Receptors, Serotonin, 616, 620 Rectal, 387, 616 Rectum, 555, 560, 567, 573, 581, 582, 589, 592, 612, 613, 616, 620 Recurrence, 559, 595, 607, 616 Red Nucleus, 616, 631 Refer, 1, 442, 561, 567, 574, 576, 580, 582, 594, 600, 601, 602, 611, 614, 616, 627 Reflex, 345, 350, 353, 579, 617 Refraction, 617, 622 Refractory, 617 Regeneration, 580, 617 Regimen, 395, 400, 405, 471, 575, 606, 608, 617 Regional enteritis, 387, 617 Regurgitation, 585, 617 Relative risk, 501, 617 Relaxant, 581, 617 Remission, 559, 595, 616, 617 Renal Circulation, 560, 617 Reproduction Techniques, 612, 617 Research Design, 617 Respiration, 372, 374, 562, 564, 598, 617 Respiratory Physiology, 617, 631 Retina, 573, 617, 618 Retinal, 573, 604, 617 Retinoids, 512, 618 Rheumatism, 618 Rheumatoid, 418, 477, 618 Rheumatoid arthritis, 418, 477, 618 Rhinitis, 563, 618 Rhythmicity, 618 Rigidity, 606, 609, 618 Risperidone, 371, 410, 618 Rod, 400, 446, 447, 618 Rodenticides, 608, 618 Rubber, 424, 549, 618 S Salicylic, 409, 618 Saliva, 11, 12, 394, 400, 413, 426, 466, 468, 471, 473, 474, 618
Salivary, 564, 573, 579, 618 Salivary glands, 564, 573, 579, 618 Salivation, 546, 618 Saponin, 343, 346, 348, 349, 618 Scans, 370, 372, 374, 511, 532, 533, 618 Schizoid, 618, 632 Schizotypal Personality Disorder, 619, 632 Scopolamine, 388, 432, 443, 558, 619 Screening, 7, 9, 400, 471, 532, 566, 619 Sebaceous, 572, 591, 619, 632 Sebaceous gland, 572, 591, 619, 632 Secretion, 418, 560, 586, 590, 592, 597, 599, 618, 619 Secretory, 151, 565, 601, 619, 625 Secretory Vesicles, 565, 619 Sedative, 564, 587, 588, 592, 594, 619, 630 Segmental, 619 Segmentation, 487, 619 Seizures, 566, 571, 583, 619 Selective estrogen receptor modulator, 482, 483, 616, 619 Semen, 481, 575, 613, 619 Semisynthetic, 598, 619 Sensitization, 452, 619 Sensor, 619 Septal, 341, 593, 619 Serous, 576, 620 Sertraline, 481, 620 Serum, 406, 417, 499, 567, 588, 594, 620 Sex Characteristics, 550, 620 Shame, 620 Shivering, 620, 626 Shock, 620, 628 Side effect, 4, 385, 392, 411, 412, 454, 458, 550, 551, 555, 563, 594, 620, 627 Sigmoid, 612, 620 Sigmoid Colon, 612, 620 Signal Transduction, 345, 620 Signs and Symptoms, 617, 620, 630 Single Person, 471, 620 Skeletal, 564, 601, 602, 620, 621 Skeleton, 549, 592, 613, 620, 621 Skull, 570, 604, 621, 625 Sleep apnea, 621, 623 Small cell lung cancer, 621 Small intestine, 565, 575, 577, 586, 588, 590, 592, 617, 621, 631 Smooth muscle, 342, 560, 561, 581, 586, 587, 599, 600, 603, 621, 624 Snoring, 621 Social Environment, 413, 621 Social Support, 7, 10, 497, 621, 623
Index 649
Sodium, 392, 560, 584, 621, 624 Soft tissue, 560, 620, 621 Solid tumor, 553, 621 Somatic, 550, 583, 593, 596, 598, 607, 612, 621, 630 Spasm, 555, 559, 621 Spatial disorientation, 574, 621 Specialist, 8, 152, 537, 621 Spectrum, 387, 458, 597, 598, 615, 621 Sperm, 565, 622 Sphincter, 592, 622 Spike, 400, 622 Spinal cord, 450, 472, 556, 563, 564, 596, 601, 607, 617, 622, 624 Spinous, 577, 592, 622 Spleen, 553, 594, 622 Spontaneous Abortion, 497, 499, 515, 516, 612, 622 Squamous, 577, 622 Squamous cell carcinoma, 577, 622 Stabilizer, 455, 622 Staging, 618, 622 Staphylococcus, 582, 598, 622 Stenosis, 622, 623 Sterility, 352, 622 Steroid, 569, 581, 622 Stillbirth, 499, 612, 622 Stimulant, 392, 413, 448, 501, 552, 555, 561, 569, 572, 586, 597, 622, 625 Stimulus, 335, 413, 574, 578, 581, 589, 591, 616, 617, 623, 626 Stomatitis, 623 Stool, 567, 589, 592, 623 Stress, 7, 150, 351, 504, 514, 516, 524, 557, 562, 565, 569, 581, 582, 600, 605, 612, 618, 623, 630 Stress management, 516, 623 Striatum, 343, 478, 603, 623 Stricture, 622, 623 Stroke, 370, 373, 380, 450, 483, 522, 533, 562, 623 Stromal, 623 Stromal Cells, 623 Strychnine, 623 Stupor, 600, 623 Styrene, 618, 623 Subarachnoid, 584, 623 Subclinical, 589, 619, 623 Subcutaneous, 3, 550, 575, 623 Subiculum, 586, 623 Sublingual, 406, 623 Subspecies, 621, 623
Substance P, 597, 619, 623 Substrate, 427, 448, 624, 629 Suction, 374, 385, 580, 624 Sulfur, 579, 597, 624 Sulfuric acid, 437, 624 Supplementation, 342, 348, 354, 458, 624 Suppression, 412, 450, 498, 624 Suppressive, 624 Sweat, 572, 624 Sweat Glands, 572, 624 Sympathetic Nervous System, 557, 565, 624 Sympathomimetic, 10, 552, 572, 574, 577, 603, 608, 624, 629 Symphysis, 564, 613, 624 Symptomatic, 564, 606, 624 Symptomatic treatment, 564, 624 Symptomatology, 624 Synapse, 339, 550, 601, 612, 624, 625, 628 Synapsis, 624 Synaptic, 331, 498, 594, 602, 620, 624, 625 Synaptic Transmission, 602, 625 Synaptic Vesicles, 625 Synaptosomes, 349, 459, 625 Synergistic, 354, 395, 515, 625, 627 Systolic, 10, 587, 625 Systolic blood pressure, 10, 625 T Tachypnea, 596, 625 Tacrine, 625 Tardive, 410, 411, 555, 625 Taste Buds, 426, 535, 625 Tear Gases, 591, 625 Telencephalon, 557, 563, 625 Temporal, 552, 584, 586, 595, 625 Temporal Lobe, 552, 625 Teratogenic, 499, 625 Testis, 578, 625 Tetracycline, 598, 625 Tetrodotoxin, 335, 347, 626 Thalamus, 573, 593, 612, 626 Thermal, 517, 560, 573, 602, 626 Thermogenesis, 517, 626 Third Ventricle, 587, 626 Thorax, 345, 549, 626, 630 Threshold, 498, 587, 609, 626 Thrombin, 580, 610, 613, 626 Thrombocytes, 610, 626 Thrombolytic, 610, 626 Thrombomodulin, 613, 626 Thrombosis, 613, 623, 626 Thromboxanes, 555, 575, 626
650 Nicotine
Thrombus, 569, 589, 600, 610, 626 Thymus, 588, 594, 626 Thyroid, 371, 374, 626, 627, 629 Thyroid Gland, 371, 374, 626, 627 Thyroid Hormones, 626, 627, 629 Thyroxine, 608, 627 Tic, 392, 411, 627 Time Management, 623, 627 Tin, 572, 606, 607, 627 Tinnitus, 514, 627, 631 Tobacco Industry, 400, 427, 444, 445, 458, 627 Tolerance, 11, 333, 348, 407, 433, 550, 566, 583, 627 Tomography, 370, 373, 568, 618, 627 Tone, 499, 501, 603, 627 Tonic, 559, 566, 627 Tonus, 627 Tooth Loss, 504, 627 Topical, 389, 475, 495, 556, 578, 586, 627 Toxicity, 436, 462, 481, 488, 491, 494, 498, 499, 597, 609, 627, 629 Toxin, 626, 627 Trace element, 560, 566, 602, 627, 628 Tracer, 371, 374, 628 Trachea, 561, 592, 608, 626, 628 Transduction, 620, 628 Transfection, 559, 628 Transfer Factor, 588, 628 Translation, 552, 628 Transmitter, 503, 549, 556, 574, 591, 596, 603, 625, 628, 629 Transplantation, 575, 588, 628 Trauma, 571, 606, 628 Treatment Failure, 497, 628 Treatment Outcome, 343, 378, 628 Trees, 618, 628 Tremor, 606, 628 Triacetin, 400, 447, 628 Tricyclic, 376, 481, 574, 588, 628 Trigeminal, 628 Trigger zone, 555, 628 Triglyceride, 628, 629 Trisomy, 553, 629 Trophoblast, 502, 559, 629 Tryptophan, 469, 470, 567, 620, 629 Tryptophan Hydroxylase, 629 Tubercle, 603, 629 Tuberculostatic, 591, 629 Tubocurarine, 582, 629 Tumor marker, 558, 629 Tumour, 629
Tunica, 599, 629 Turpentine, 383, 629 Type 2 diabetes, 514, 629 Tyramine, 342, 344, 558, 599, 629 Tyrosine, 331, 349, 359, 470, 574, 629 U Ulcerative colitis, 4, 330, 387, 495, 589, 612, 615, 629 Umbilical Arteries, 629 Umbilical Cord, 516, 565, 629 Unconscious, 571, 588, 630 Uraemia, 606, 630 Urea, 624, 630 Urease, 602, 630 Urethra, 613, 630 Urinary, 564, 583, 589, 619, 630, 632 Urinate, 374, 630 Urine, 371, 374, 408, 409, 463, 559, 574, 589, 630 Urogenital, 478, 583, 630 Urticaria, 563, 587, 630 Uterus, 500, 549, 563, 569, 571, 576, 596, 600, 605, 612, 630 Uvula, 621, 630 V Vaccination, 362, 630 Vaccine, 510, 512, 550, 614, 630 Vagina, 563, 572, 596, 630 Vagus Nerve, 355, 630 Valerian, 470, 630 Vasculitis, 606, 630 Vasodilator, 560, 574, 586, 602, 630 Vasomotor, 631 VE, 330, 367, 369, 378, 631 Vein, 371, 591, 603, 629, 631 Venous, 333, 423, 559, 603, 613, 631 Venous blood, 559, 631 Venter, 631 Ventilation, 404, 631 Ventral, 331, 333, 587, 603, 631 Ventral Tegmental Area, 331, 333, 631 Ventricle, 352, 552, 562, 586, 603, 615, 625, 626, 631 Ventricular, 515, 631 Venules, 559, 576, 631 Vertebrae, 622, 631 Vesicular, 581, 584, 598, 631 Vestibulocochlear Nerve, 627, 631 Vestibulocochlear Nerve Diseases, 627, 631 Veterinary Medicine, 384, 523, 631 Villi, 502, 631
Index 651
Virulence, 627, 631 Virus, 549, 563, 577, 586, 590, 610, 628, 632 Visceral, 557, 583, 593, 630, 632 Visceral Afferents, 557, 583, 630, 632 Viscosity, 383, 632 Vital Statistics, 559, 632 Vitreous, 573, 617, 632 Vitreous Hemorrhage, 573, 632 Vitro, 334, 336, 340, 343, 345, 347, 500, 576, 589, 632 Vivo, 632 Volition, 591, 632 Vomica, 623, 632 Vulgaris, 351, 549, 632 W War, 507, 599, 632 Warts, 586, 632
White blood cell, 554, 584, 592, 594, 595, 599, 602, 610, 632 Windpipe, 608, 626, 632 Womb, 630, 632 Wound Healing, 418, 477, 580, 595, 632 X Xanthine, 398, 437, 632 Xenobiotics, 632 Xenograft, 553, 632 X-ray, 560, 562, 568, 591, 599, 603, 615, 616, 618, 622, 633 X-ray therapy, 591, 633 Y Yeasts, 581, 608, 633 Z Zebrafish, 335, 633 Zygote, 568, 633 Zymogen, 613, 633
652 Nicotine
Index 653
654 Nicotine
