ROSIGLITAZONE 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
ii
ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2004 by ICON Group International, Inc. Copyright 2004 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., 1960Rosiglitazone: 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: 0-597-84613-8 1. Rosiglitazone-Popular works. I. Title.
iii
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:
[email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International, Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this book.
iv
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 rosiglitazone. 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.
v
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.
vi
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
vii
Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON ROSIGLITAZONE........................................................................................ 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Rosiglitazone................................................................................. 4 E-Journals: PubMed Central ....................................................................................................... 27 The National Library of Medicine: PubMed ................................................................................ 27 CHAPTER 2. NUTRITION AND ROSIGLITAZONE .............................................................................. 51 Overview...................................................................................................................................... 51 Finding Nutrition Studies on Rosiglitazone................................................................................ 51 Federal Resources on Nutrition ................................................................................................... 55 Additional Web Resources ........................................................................................................... 55 CHAPTER 3. CLINICAL TRIALS AND ROSIGLITAZONE .................................................................... 57 Overview...................................................................................................................................... 57 Recent Trials on Rosiglitazone..................................................................................................... 57 Keeping Current on Clinical Trials ............................................................................................. 61 CHAPTER 4. PATENTS ON ROSIGLITAZONE .................................................................................... 63 Overview...................................................................................................................................... 63 Patents on Rosiglitazone.............................................................................................................. 63 Patent Applications on Rosiglitazone .......................................................................................... 65 Keeping Current .......................................................................................................................... 69 CHAPTER 5. BOOKS ON ROSIGLITAZONE ........................................................................................ 71 Overview...................................................................................................................................... 71 Chapters on Rosiglitazone............................................................................................................ 71 CHAPTER 6. PERIODICALS AND NEWS ON ROSIGLITAZONE .......................................................... 73 Overview...................................................................................................................................... 73 News Services and Press Releases................................................................................................ 73 Academic Periodicals covering Rosiglitazone .............................................................................. 77 CHAPTER 7. RESEARCHING MEDICATIONS .................................................................................... 79 Overview...................................................................................................................................... 79 U.S. Pharmacopeia....................................................................................................................... 79 Commercial Databases ................................................................................................................. 80 APPENDIX A. PHYSICIAN RESOURCES ............................................................................................ 83 Overview...................................................................................................................................... 83 NIH Guidelines............................................................................................................................ 83 NIH Databases............................................................................................................................. 85 Other Commercial Databases....................................................................................................... 87 APPENDIX B. PATIENT RESOURCES ................................................................................................. 89 Overview...................................................................................................................................... 89 Patient Guideline Sources............................................................................................................ 89 Finding Associations.................................................................................................................... 91 APPENDIX C. FINDING MEDICAL LIBRARIES .................................................................................. 93 Overview...................................................................................................................................... 93 Preparation................................................................................................................................... 93 Finding a Local Medical Library.................................................................................................. 93 Medical Libraries in the U.S. and Canada ................................................................................... 93 ONLINE GLOSSARIES.................................................................................................................. 99 Online Dictionary Directories ..................................................................................................... 99 ROSIGLITAZONE DICTIONARY............................................................................................. 101
viii Contents
INDEX .............................................................................................................................................. 151
1
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 rosiglitazone 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 rosiglitazone, 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 rosiglitazone, 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 rosiglitazone. 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 rosiglitazone, 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 rosiglitazone. The Editors
1
From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.
3
CHAPTER 1. STUDIES ON ROSIGLITAZONE Overview In this chapter, we will show you how to locate peer-reviewed references and studies on rosiglitazone.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and rosiglitazone, 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 “rosiglitazone” (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: •
Prospective, Randomized Comparison of the Metabolic Effects of Pioglitazone or Rosiglitazone in Patients with Type 2 Diabetes Who Were Previously Treated with Troglitazone Source: Diabetes Care. 25(4): 708-711. April 2002. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This article reports on a study undertaken to characterize potential differences in glycemic (blood glucose) control, plasma lipid (fats) level, and weight in a cohort of patients previously treated with troglitazone (TROG) who were switched to either pioglitazone (PIO) or rosiglitazone (ROSI). After a 2 week washout period from TROG, 186 patients were randomly assigned to receive either PIO or ROSI. A total of
4
Rosiglitazone
127 patients completed follow up: 67 individuals in the PIO group (32 women, 35 men) and 60 individuals in the ROSI group (33 women, 27 men). There were no significant differences in gender mix, age, weight, fasting lipid profile, or HbA1c (glycosylated hemoglobin, a measure of blood glucose levels over time) between the ROSI and PIO groups. After 4 months of randomized treatment, no change in HbA1c from baseline between or within groups was noted. Both groups experienced an equal and significant increase in weight from baseline of approximately 2.0 kilograms. Thiazolidinedione and HMB-CoA reductase inhibitor therapy had significant and independent effects on lipid profile. Significant improvements in lipid profile were noted in the PIO group, whereas none were detected with conversion to ROSI. The authors conclude that differing effects on lipid profile were apparent after random conversion from TROG to either PIO or ROSI, despite similar weight increase and glycemic control. The clinical significance of these differences remains to be determined, and further comparative research is warranted. 1 figure. 3 tables. 21 references. •
Evaluation of Liver Function in Type 2 Diabetic Patients During Clinical Trials: Evidence That Rosiglitazone Does Not Cause Hepatic Dysfunction Source: Diabetes Care. 25(5): 815-821. May 2002. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: Troglitazone treatment has been associated with idiosyncratic hepatic (liver) reaction leading to liver failure and death in some patients. This study was undertaken to determine if this idiosyncratic liver toxicity is molecule-specific or a thiazolidinedione class effect, based on liver enzyme data collected prospectively during phase 2 and 3 clinical trials with rosiglitazone, a new, potent, and specific member of the thiazolidinedione class. The study comprised more than 6,000 patients aged 30 to 80 years who have type 2 diabetes (22 different research studies). At baseline, 5.6 percent of the patients with type 2 diabetes had serum ALT values (a measure of liver function) between 1.0 and 2.5 times the upper limit of the reference range. On antidiabetic therapy, most of the patients (approximately 83 percent) had a decrease in ALT values, many into the normal range. The authors conclude that no evidence of hepatotoxic effects was observed in studies that involved 5,006 patients taking rosiglitazone as monotherapy or combination therapy. Poorly controlled patients with type 2 diabetes may have moderate elevations of serum ALT that will decrease with improved glycemic control during treatment with rosiglitazone or other antihyperglycemic agents. 4 tables. 44 references.
Federally Funded Research on Rosiglitazone The U.S. Government supports a variety of research studies relating to rosiglitazone. 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.
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
5
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 rosiglitazone. 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 rosiglitazone. The following is typical of the type of information found when searching the CRISP database for rosiglitazone: •
Project Title: ANDROGEN EFFECTS AND INSULIN RESISTANCE IN HIV DISEASE Principal Investigator & Institution: Grinspoon, Steven K.; Associate Professor of Medicine; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2003; Project Start 15-MAR-2003; Project End 29-FEB-2008 Summary: (provided by applicant): The goal of this application is to support my professional development as a clinical investigator and successful mentor to junior faculty and fellows in patient-oriented research My research focus has been to investigate the effects of nutritional status on neuroendocrine function, and as such, I have used HIV disease as a relevant disease model, with two funded NIH R01 grants for which I am the PI. The three Specific Aims of this grant stem from a significant body of work accomplished over the past few years demonstrating hypogonadism in HIVinfected women and a severe insulin resistance pattern in HIV-infected patients with lipodystrophy In these funded studies, I will investigate the mechanisms of androgen deficiency and also the effects of long-term physiologic testosterone replacement in this population Furthermore, I will study the mechanisms of insulin resistance, investigating the critical role of increased lipolysis and the effects of thiazolidinediones in this population The grant for the first Specific Aim, to study the effects of androgens in HIVinfected women, will expire at the end of this year, and a follow-up proposal, recently submitted will further investigate adrenal androgen shunting and DHEA in this population Preliminary data in this regard show a novel effect of HIV on adrenal metabolism, with shunting toward cortisol and away from androgen production The grant for the third Specific Aim is funded until 2005 I have had good success as a mentor, with two recent K-23 awardees and six former or current trainees There has been significant interest in my research from Endocrine Fellows and also from Fellows in Harvard Nutrition Division The Institutional Environment at the MGH, with a strong and diverse Endocrine Division, GCRC, and Center for AIDS Research is outstanding The Department of Medicine has made a substantial commitment toward my development as a clinical researcher responsible for training a large number of fellows However, it is clearly necessary to reduce my clinical activities in order to devote sufficient time to the training and mentoring of junior faculty and fellows The Midcareer Investigator Award in Patient Oriented Research is an ideal mechanism to ensure the necessary support to reduce clinical and administrative responsibilities, and ensure my continued success as a mentor and clinical researcher. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: BONE MARROW FAT AND OSTEOPENIA IN HIV LIPODYSTROPHY Principal Investigator & Institution: Huang, Jeannie S.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 15-APR-2002; Project End 31-AUG-2002
6
Rosiglitazone
Summary: (provided by applicant): The HIV lipodystrophy syndrome is a recognized complication of potent antiretroviral therapy that is characterized by fat redistribution. Prior research has shown that HIV-infected men with lipodystrophy are at risk for osteopenia. In addition, we have preliminary evidence that these individuals have reduced bone marrow fat as compared to age and BMI matched control subjects. This novel finding may reflect the co- existence of both reduced adipogenesis and osteogenesis in this group of individuals. Further studies are needed to verify this observation and to characterize the relationship between intramarrow fat and bone density in this population. This determination is critical for the establishment of appropriate therapy for both lipoatrophy and osteopenia in HIV-infected individuals with lipodystrophy. To investigate this hypothesis, MR spectroscopy of the bone marrow and direct measurement of intramarrow fat content by bone biopsy will be compared in both HIV-infected patients with and without lipodystrophy and in healthy controls. These determinations will be correlated with direct (bone biopsy) and indirect (QCT and DXA) measurements of bone density to determine the relationship between intramarrow fat and bone mass. Furthermore, possible gender differences will be evaluated by comparing these same indices, body composition, and sex steroid levels, in men and women with the HIV lipodystrophy syndrome. We hypothesize that the adipocyte is integral in the coordination of bone turnover and may thus serve as a promising therapeutic target in the treatment of osteopenia in HIV lipodystrophy. In the second aim of this proposal, we will investigate whether the use of a PPARgamma agonist, rosiglitazone, will effectively increase both bone marrow fat and bone density in subjects with HIV lipodystrophy. The potential benefits of rosiglitazone therapy include restoration of bone density, improvement of insulin resistance, and reversal of the changes in body fat distribution in the HIV lipodystrophy syndrome. In summary, this proposal will investigate the relationship between intramarrow fat and osteopenia in the HIV lipodystrophy syndrome and will evaluate a novel therapeutic strategy to treat and prevent the potential long- term morbidity associated with reduced bone density in this expanding population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EFFECTS OF RHGH IN ADULTS WITH VISCERAL OBESITY AND IGT Principal Investigator & Institution: Attallah, Hamdee Y.; Medicine; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2003; Project Start 04-OCT-2003 Summary: (provided by applicant): The long-term objective is to determine whether prolonged GH administration can reduce postprandial glucose levels in viscerally obese adults with impaired glucose tolerance IGT). IGT increases the risk for developing 2 major health problems, type 2 diabetes mellitus and cardiovascular disease, and this risk decreases when postprandial glucose reduction is achieved. The specific aim is to determine if GH administration in viscerally obese adults with TGT will result in (1) a reduction in visceral fat and (2) lower postprandial glucose levels after a 75 gm glucose load. Men and women between the ages of 40 and 75 with visceral obesity and IGT will be recruited to participate. During weeks 0-8, subjects will receive a thiazolinedione (TZD) or oral placebo to determine if TZDs can overcome the transient insulin resistant effects of GH during the first few weeks of treatment. During weeks 8-32, recombinant human GH or a subcutaneous placebo will be co-administered with TZD or placebo. Changes in visceral body tat will be determined with CT scan and waist circumference
Studies
7
measurements. Changes in postprandial glucose levels before and after 6 months of GH treatment will be determined using a 75 gm oral glucose tolerance test. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ENDOMETRIAL CANCER CHEMOPREVENTION STRATEGY FOR OBESE WO Principal Investigator & Institution: Lu, Karen H.; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2008 Summary: Obesity affects over 25% of adult women in the United States and continues to increase in prevalence. Minority women are disproportionately affected by obesity: 37% of African American women and 33% of Mexican American women are obese (body mass index equal to or more than 30 kg/m2). In addition to cardiovascular risks, obese women clearly are at increased risk for developing endometrial cancer. Obese women have a 9-10% lifetime risk of endometrial cancer and account for almost 50% of all cases. It is presumed that the increased peripheral conversion of adrenal steroids to estrone in adipose tissue, the increased bioavailability of adrenal steroids, and the increased bioavailablity of free estrogens due to decreased sex hormone binding globulin (SHBG) contribute to a "hyper-estrogenic state", resulting in the development of endometrial hyperplasia and endometrial cancer. However, excess circulating estrogens are unlikely to fully account for this increased cancer risk. We hypothesize that insulin resistance and hyperinsulinemia are causally related factors that promote endometrial carcinogenesis by altering estrogen regulated pathways in the endometrium. In addition, we hypothesize that correction of insulin resistance may be a rational cancer chemopreventive strategy for obese women. We plan to identify, using an animal model of obesity and insulin resistance, molecular markers in the endometrium associated with dysregulated estrogen-controlled growth pathways. A clinical chemoprevention trial will be performed to determine if normalization of insulin resistance is accompanied by modulation of surrogate biomarkers. Aim 1: To test the hypothesis that obesity and insulin resistance increase estrogen-dependent proliferation in the endometrium. Animal models of obesity and insulin resistance will be used to evaluate the effects of obesity on estrogen-regulated endometrial gene expression. In addition, the ability of insulin sensitizers to reverse this effect will be studied. Specific genes involved in estrogen-regulated proliferation pathways will be examined by quantitative PCR, including hormone receptors and co-activators, and genes involved in the Wnt pathway, IGF pathway, TGF-beta and retinoid pathway. Aim 2: To identify novel genes and pathways associated with insulin resistance and estrogenization, and to identify relevant and specific biomarkers that are modulated by normalization of insulin resistance. Expression profiling with cDNA microarrays will be used to explore the effects of obesity and insulin resistance on both estrogen-dependent and estrogenindependent endometrial gene expression. In addition, specific biomarkers of the endometrium that are modulated by insulin-sensitizers will be identified. Aim 3: To assess the ability of an insulin-sensitizing agent to modulate surrogate endometrial biomarkers in a post-menopausal cohort of obese, insulin resistant women. The postmenopausal cohort includes obese women (body mass index equal to or more than 30kg/m2) who demonstrate insulin resistance based on an oral glucose tolerance test, but who do not fulfill criteria for Type II Diabetes. We hypothesize that rosiglitazone, an insulin-sensitizing agent, will modulate relevant endometrial proliferation biomarkers. In pre-and post-treatment endometrial biopsies, we will assess expression levels of genes involved in estrogen-regulated gro,aedapathways, specific biomarkers as
8
Rosiglitazone
defined in Aim 2, and histologic and proliferation markers. As secondary endpoints, we will establish a point estimate of the baseline frequency of endometrial abnormalities in this cohort and we will determine changes in serum levels of estradiol, estrone, testosterone, DHEA-S and SHBG in obese, post-menopausal women taking rosiglitazone. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ETIOLOGY OF OVARIAN HYPERANDROGENEMIA IN PCOS Principal Investigator & Institution: Mccartney, Christopher R.; Physiology; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2002; Project Start 01-SEP-2002 Summary: (provided by applicant): PCOS is a disorder marked by excessive ovarian androgen production, but its etiology is unknown. Provocative ovarian testing involving markedly supraphysiologic LH stimuli have produced abnormal steroid responses in PCOS, leading to the theory that inherent abnormalities of ovarian steroidogenesis underlie PCOS. We propose to further explore this hypothesis in specific aim 1 by delineating ovarian steroid responses to physiologic LH stimuli, thus allowing the construction of LH-steroid dose-response curves in both normal women and women with PCOS. Consistent features of PCOS include persistent LH hypersecretion, insulin resistance/hyperinsulinemia, and hyperandrogenemia, and some or all of these factors may play a role in causing and/or perpetuating the abnormalities of ovarian steroidogenesis. In specific aim 2, studies will investigate the relative roles of persistent LH hypersecretion, hyperinsulinemia, and ovarian hyperandrogenemia in the maintenance of abnormal ovarian steroid responses to LH in PCOS. The ovarian steroid response to physiologic LH stimulation will be examined 6 weeks after reduction of LH using the gonadotropin-releasing hormone agonist leuprolide; 6 weeks after reduction of hyperinsulinemia using metformin or rosiglitazone; and 6 weeks after androgen receptor blockade using flutamide. The results of these studies will help elucidate mechanisms involved in ovarian hyperandrogenemia in women with PCOS. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: GCRC - CAP - JOAN C. LO, MD Principal Investigator & Institution: Debas, Haile T.; Dean, School of Medicine; Medicine; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 01-OCT-1974; Project End 30-NOV-2002 Summary: (provided by applicant): Despite the dramatic reduction in HIV-associated morbidity and mortality accompanying the introduction of highly active antiretroviral therapy (HAART), there has emerged a concomitant recognition of important metabolic complications involving abnormalities of fat distribution, carbohydrate and lipid metabolism, and bone mineralization. Given the potential implications of these findings for risk of cardiovascular disease and osteoporotic fractures, there exists a need to better characterize the epidemiology and underlying mechanisms of these syndromes and to evaluate potential targeted interventions. The current application expands upon the investigators' previous studies in this area and will address many of these issues through three specific aims: 1) To test the hypotheses that the thiazolidinediones improve glucose homeostasis and increase subcutaneous adipose tissue in patients with HIV-associated lipoatrophy, they will measure insulin sensitivity, glucose tolerance, hepatic glucose production, and total, visceral and subcutaneous fat in patients with
Studies
9
HIV-associated lipoatrophy before and after six months of rosiglitazone therapy. Associated changes in lipid metabolism will be assessed by measuring lipid and lipoprotein levels, fat clearance, whole-body lipolysis, and hepatic de novo lipogenesis. 2) To test the hypothesis that low-dose growth hormone is effective in the treatment of HIV-associated fat accumulation, they will measure total, trunk, and visceral fat before and after six months of growth hormone at 1 mg/day. To determine the effects of growth hormone on carbohydrate and lipid metabolism, they will measure insulin sensitivity, glucose tolerance, hepatic glucose production, lipid and lipoprotein levels, fat clearance, whole body lipolysis, and hepatic de novo lipogenesis before and during growth hormone treatment. 3) To test the hypothesis that treatment with HAART is associated with lower bone mineral density (BMD) in HIV-infected patients and to identify independent patient- and disease-related predictors of low bone density, they will perform cross-sectional and longitudinal measurements of BMD, biochemical markers of bone turnover, and related metabolic factors in patients about to initiate to HAART and in patients who are stable on HAART with effective viral suppression. A clearer understanding of these metabolic disorders and potential targeted interventions may impact significantly on the therapeutic management of HIV infection. INVESTIGATORS:Dr. Joan Lo received the M.S. degree in biochemistry at UCLA and the M.D. degree from Harvard Medical School in 1993. She was a resident in Internal Medicine at Brigham and Women's Hospital from 1993 to 1996. In 1996, she became a fellow in endocrinology and metabolism at the UCSF focusing her studies under the mentorship of Dr. Morris Schambelan, Chief of Endocrinology and Program Director of the GCRC and working also with Dr. Kathleen Mulligan at the San Francisco General Hospital GCRC. Her initial studies focused on altered fat distribution in HIV infected patients and she received a CAP award to extend these studies in an intensive clinical metabolic investigation using glucose clamp methodology, carbohydrate fat tolerance and body composition measurements. She has eight publications as a CAP recipient; three as first author (although two are reviews). During the first couple of years of her CAP award, she initiated pilot studies in the use of growth hormone for excess visceral adiposity in HIV infected patients with fat accumulation; this was the first study to carefully evaluate the effects of growth hormone on both insulin action and glucose metabolism and on hepatic carbohydrate and liver metabolism in this population. She has also published a review of reproductive function of HIV infection and has collaborated on very important and novel studies of the effects of protease inhibitors on insulin resistant and HIV negative individuals. She has had very good productivity in her initial years as a CAP recipient; the current proposal seeks to extend these studies both in fat accumulation and fat loss in HIV infected patients as well as initiating bone studies. Her support letters are very strong. She clearly is an excellent candidate. It is of note that her letter from Dr. Schambelan suggests that she is likely to receive a faculty appointment at San Francisco General Hospital in the Division of Endocrinology, focusing particularly on bone abnormalities since there is currently no member of the faculty who studies bone. Her sponsor/mentor is Dr. Morris Schambelan. He is Professor of Medicine at UCSF and the Program Director of the GCRC. Dr. Schambelan is a very well-established investigator in endocrinology who for the last 10-12 years has concentrated on the pathogenesis and treatment of metabolic and endocrine disturbances in patients with HIV and AIDS and his group at San Francisco General Hospital is widely recognized as one of the world leaders of investigation in this field. His group has made major contributions to our understanding of these abnormalities and potential therapies for HIV infected patients. In addition to being Program Director for the GCRC, Dr. Schambelan is currently a principal investigator on three NIH R01s and co-investigator on a fourth. It is interesting to note that one of the R01s overlaps in Aims 1 and 2 for Dr. Lo's proposals; however, Dr. Schambelan makes it clear that his
10
Rosiglitazone
grant will make available supplies and other costs that could not be covered in the CAP award. Dr. Schambelan is an outstanding mentor. He has a clear and strong record in training young investigators and his record already with Dr. Lo is superb. In addition, Dr. Dolores Shoback, Professor of Medicine at UCSF, would provide mentorship for the studies in bone metabolism. Dr. Shoback is well qualified to provide insight and support for these studies. However, her involvement in the design of the proposed studies is unclear, and her expertise in the epidemiology of osteoporosis is quite limited. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC VARIATION IN DRUG TARGETS FOR TYPE 2 DIABETES Principal Investigator & Institution: Florez, Jose C.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2004; Project Start 01-MAR-2004; Project End 28-FEB-2009 Summary: (provided by applicant): The Principal Investigator in this proposal is an M.D., Ph.D. post-doctoral fellow subspecializing in endocrinology who is interested in becoming an independent translational genomics investigator. He plans to extend the findings of diabetes genetics research into the clinical arena, and thus contribute to understand the heterogeneity of type 2 diabetes (T2DM), the impact of common genetic variation on the development of diabetes and the role of an individual's genetic profile in therapeutic response. In order to do so, he is currently training in Dr. David Altshuler human genetics laboratory at the Massachusetts General Hospital (MGH), which has intellectual and technological ties to the Whitehead Institute/Massachusetts Institute of Technology Center for Genome Research. He is also sponsored by Dr. David Nathan, the head of the MGH Diabetes Center and an international leader in diabetes clinical trials. This proposal aims to study the role of common variation in genes encoding drug targets for T2DM. Type 2 diabetes is a polygenic disease, and recent evidence has implicated single nucleotide polymorphisms (SNPs) in the peroxisome proliferatoractivated receptor-gamma (PPARG, a target for thiazolidinediones) and the sulfonylurea receptor complex in the pathogenesis of the disease. A T2DM association of common variants in AMP kinase (a presumed drug target for metformin) has not been reported. During the initial phase of the project, the haplotype structure of the genes for the sulfonylurea receptor, its associated potassium channel and the five known subunits of AMP kinase will be elucidated. Haplotype tag SNPs will be tested for association with T2DM in several family-based and case-control panels totalling 7000 subjects. The role of any associated SNPs and the Pro12Ala variant in PPARG in the development of T2DM and the response to various drugs will be studied in the Diabetes Prevention Program patient sample. In collaboration with Dr. Deirdre Blake, the impact of genetic variation in the above genes on response to short-term therapy will be measured by studying multiple parameters of human beta cell function. Finally, whether variability in long-term response to hypoglycemic therapy can be observed in clinical practice will be determined in a clinical study. This proposal should serve as the foundation for a large pharmacogenomics trial designed to evaluate the feasibility of genetically-tailored therapy in T2DM. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: HIV-1 PROTEASE INHIBITORS AND VASCULAR RISK Principal Investigator & Institution: Shankar, Sudha S.; Medicine; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008
Studies
11
Summary: (provided by applicant): HIV-1 protease inhibitors (PI)-based Highly Active Antiretroviral Therapy (HAART) has increased life expectancy in the HIV-infected. Recently, there has been increasing concern over reports of abnormal glucose and lipid metabolism, endothelial dysfunction, as well as even reports of cardiac events in HIVinfected patients receiving PI-based HAART. With increasing longevity in this population that uses PIs for lifelong treatment, this portends ominous increases in morbidity, mortality and health care costs from therapy-based complications such as diabetes and coronary disease. However, some of these complications have been reported in untreated patients, as well as in those on PI-free HAART. Thus, it remains to be defined if the heightened vascular risk is due to PI alone, HIV infection alone, or an interaction between the two. Recent preliminary data from our laboratory suggest that in HIV-negative non-obese subjects, the PI indinavir (IDV) induces endothelial dysfunction as well as insulin resistance (IR). We propose to dissect out the sites of IDVinduced IR, the role of IDV in the induction of endothelial dysfunction in the absence of infection, IR as the mechanism underlying IDV-induced endothelial dysfunction, and the role of adipocyte dysfunction in the above metabolic and vascular changes, and its prevention. We will study insulin sensitivity, beta cell function, endothelial function, lipid parameters, newly recognized vascular risk factors as well as adipocyte differentiation in healthy HIV-negative non-obese subjects before and after 4 weeks of IDV/placebo, and the effect of prevention of impaired adipocyte function on the above parameters before and after 4 weeks of co-administration of IDV and the thiazolidinedione, rosiglitazone in a similar group of subjects. We will test the following hypotheses: 1) IDV induces IR at the level of muscle, fat and liver, and impairs beta cell function. 2) IDV induces endothelial dysfunction, partly through induction of IR. 3) IDV induces changes in IR-related qualitative lipid parameters and non-traditional vascular risk factors, thus supporting IR as the basis for the endothelial dysfunction. 4) Rosiglitazone will prevent IDV-induced adipocyte changes, and thus IR as well as endothelial dysfunction. Thus, results from our studies will help define IDV-associated vascular risk, the underlying mechanism, and a possible means of preventing the same. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HYPERINSULINEMIA AND THE PATHOGENESIS OF NASH Principal Investigator & Institution: Neuschwander-Tetri, Brent A.; Internal Medicine; St. Louis University St. Louis, Mo 63110 Timing: Fiscal Year 2002; Project Start 20-MAY-2002; Project End 30-APR-2007 Summary: Non-alcoholic fatty liver disease (NAFL or NAFLD) and its subset, nonalcoholic steatohepatitis (NASH) are increasingly recognized as common forms of liver disease. In the absence of concomitant cellular injury, fatty liver is a benign condition that may cause elevated liver enzymes, fatigue and abdominal pain. MASH is identified by the presence of fat in the liver plus hepatocellular injury, inflammation and varying degrees of liver fibrosis. It afflicts up to 3% of adults n the United States and one third of these people may be at risk for developing cirrhosis. NASH also affects children, although its prevalence in the pediatric population is less well defined. Currently 2% of liver transplants performed in the United States are performed because of known diagnosis of NASH. Insulin resistance, with its major associated diseases of obesity and Type 2 diabetes, is emerging as a major coexisting condition. This application proposes two clinical studies to be performed in the context of a cooperative clinical research network to achieve the long-term goals of establishing the role of hyperinsulinemia in the pathogenesis of NASH and identifying rational and effect strategies to prevent and cure NASH. These goals will be addressed by specific aims of this proposal that seek to
12
Rosiglitazone
better understand the prevalence of NASH in hyperinsulinemic patients and establish whether reducing insulin levels pharmacologically improves the necroinflammatory changes associated with NASH. Two clinical studies are proposed. The first study establishes the prevalence of NASH in patients with hyprinsulinemia and imaging evidence of fatty liver. A secondary goal of the prevalence study is to establish racial differences in the risk for developing NASH because NASH may be underrepresented or underdiagnosed in African Americans. Enrollment will include adequate African Americans to allow subgroup analysis. The second proposed study is to a 48 week treatment trail of patients with NASH using the PPAR-gamma ligand rosiglitazone and, if needed to control hyperinsulinemia, metformin. Liver biopsies of patients recruited from all Clinical Centers will be compared to liver biopsies of patients treated with the standard recommendation of weight reduction. The primary endpoint will be improvement in the liver biopsy necroinflammatory score. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IN VIVO EVALUATION OF MYOCARDIAL LIPIDS Principal Investigator & Institution: Szczepaniak, Lidia S.; Internal Medicine; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2007 Summary: (provided by applicant): As we have became the fattest nation in the world, obesity is an increasingly important cause of myocardial morbidity and mortality in the United States. Obesity indirectly contributes to heart disease by increasing plasma lipids and predisposing to diabetes and hypertension (i.e. traditional cardiovascular risk factors). In addition, recent work from Roger Unger advances the novel hypothesis that obesity per se constitutes a direct cause of left systolic ventricular dysfunction and hypertrophy by promoting cardiac steatosis. Major Hypothesis: Cardiac steatosis is an integral feature of human obesity, contributing to decrease of LV systolic function. I further hypothesize that these functional abnormalities of the human heart are provoked by the development of non-insulin dependent diabetes mellitus (type 2 diabetes) and can be reversed by treatment with Thiazolidinediones. Specific Aims: In human subjects without heart disease, I will measure lipid deposition in the ventricular septum using double gated localized proton nuclear magnetic resonance (1H NMR) as well as LV systolic function with magnetic resonance imaging (MRI) to accomplish the following specific aims: Aim 1: To document the intra-subject reproducibility of the 1H NMR measurement of intra-myocardial lipid content. Aim 2: To establish the relation between adiposity and myocardial lipid deposition over a wide range of BMI and determine the impact of gender, and ethnicity on these relations. Aim 3: To determine if intramyocardial lipid deposition is greater in individuals with IGT and insulin resistance than in these with normal glucose tolerance matched for BMI, age, gender and ethnicity. I hypothesize that the greater myocardial lipid in diabetic and prediabetic individuals will be accompanied by decreased LV systolic function. Aim 4: To perform randomized prospective study to test the hypothesis that the elevated myocardial lipid content and decreased systolic LV function can be reversed or minimized by the treatment with Thiazolidinediones. In contrast, I predict that functional cardiac abnormalities will be unaffected when diabetic subjects are treated with sulfonylureases that have no effect on PPAR-gamma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
Studies
•
13
Project Title: INFLAMMATION AND INSULIN RESISTANCE IN PAD Principal Investigator & Institution: Creager, Mark A.; Associate Professor of Medicine; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 22-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): Patients with peripheral arterial disease (PAD) frequently have functional limitations and symptoms of claudication that impact adversely on their quality of life. Many progress to critical limb ischemia requiring revascularization. Vascular inflammation and insulin resistance are two important and interdependent conditions that are associated with atherosclerosis. Moreover, both inflammation and insulin resistance cause abnormalities in vascular function and insulin resistance interferes with skeletal muscle metabolism. As such, inflammation and insulin resistance provide attractive targets for therapy that could potentially ameliorate the development of symptomatic PAD or improve the function and clinical outcomes of patients with PAD. Accordingly, the applicants propose three specific aims to determine whether inflammation and insulin resistance contribute to the functional and clinical consequences of PAD. First, a prospective, nested, case-control evaluation will be performed to test the hypothesis that baseline plasma levels of inflammatory cytokines (e.g. interleukin (IL)-4, IL-6, IL-18, macrophage inhibiting cytokine-1, CD 40 ligand) among healthy men are associated with the development of future symptomatic PAD. Second, to test the hypothesis that inflammation and insulin resistance contribute to reduced walking distance in patients with intermittent claudication by impairing vascular reactivity and skeletal muscle metabolic function, plasma markers of inflammation and insulin resistance, endothelium-dependent and independent vasodilation (by vascular ultrasonography) and skeletal muscle glucose utilization (by [18F] FDG positron emission tomography) will be measured before and after 12 weeks of treatment with rosiglitazone, atorvastatin or placebo in a 2x2 factorial design protocol. Third, to test the hypothesis that inflammation and insulin resistance are associated with the incidence and progression of vein graft disease in patients undergoing lower extremity vein bypass, functional and morphologic changes in vein grafts (measured by ultrasound and magnetic resonance imaging) will be assessed and related to inflammation and insulin resistance and to a composite clinical outcome of graft occlusion, re-intervention or major amputation. It is anticipated that the findings from this investigation will uncover novel pathophysiologic mechanisms and foster a new paradigm for the treatment of PAD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: INFLAMMATION, ATHEROSCLEROSIS
THE
METABOLIC
SYNDROME
AND
Principal Investigator & Institution: Reilly, Muredach P.; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2007 Summary: (provided by applicant): The prevalence of overweight/obesity has risen in the United States. The resulting increase in the metabolic syndrome affects approximately 25% of adults over age 20 and almost 50% over age 50. This state is characterized by a clustering of cardiovascular risk factors including visceral adiposity, insulin resistance, low HDL cholesterol and a systemic pro-inflammatory state that confers a marked increased risk of both type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD). The molecular mechanisms linking obesity, the metabolic syndrome and ASCVD are poorly understood, however, innate immunity
14
Rosiglitazone
appears to play a proximal pathophysiological role. Acute activation of innate immunity during endotoxemia generates an inflammatory, metabolic and dyslipidemic response that is remarkably similar to metabolic syndrome. Adipocytes, like monocytes, can mediate a robust inflammatory response to acute stresses. Adipose tissue produces a variety of adipocytokines (TNF(, IL6, leptin, adiponectin and resistin) that mediate chronic inflammatory and proatherosclerotic responses in the metabolic syndrome. In animals, obesity amplifies the inflammatory and metabolic responses to endotoxemia but the effect on evoked inflammation in humans has not been addressed. Potential proatherosclerotic mechanisms in endotoxemia and the metabolic syndrome include cytokine signaling, dyslipidemia, insulin resistance and oxidant stress. Changes in lipoproteins, particularly HDL, may reduce macrophage cholesterol efflux and the antiatherosclerotic reverse cholesterol transport pathway. The effect of endotoxemia or the metabolic syndrome on specific macrophage cholesterol efflux pathways in humans is unknown. We and others have used controlled administration of endotoxin in humans to study the pathophysiology of acute inflammation and its modulation in vivo. We propose to use this model to (1) systematically assess proatherosclerotic pathways during activation of innate immunity in the metabolic syndrome, (2) characterize the effect of innate immune activation on specific macrophage cholesterol efflux pathways and (3) determine the capacity of a candidate metabolic syndrome therapy, the PPARg agonist Rosiglitazone, to modulate pro-atherosclerotic response in the metabolic syndrome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INSULIN AND ROSIGLITAZONE IN LH INDUCED OVARIAN RESPONSE Principal Investigator & Institution: Chang, R Jeffrey.; Professor & Chairman; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 920930934 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: INSULIN RESISTANCE AND CNS FUNCTION IN TYPE 2 DIABETES Principal Investigator & Institution: Craft, Suzanne; Professor; Psychiatry and Behavioral Scis; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2005 Summary: (provided by applicant): Type 2 diabetes mellitus (T2DM) is caused by insulin resistance (IR) and inadequate insulin secretion. T2DM affects one in five Americans over age 60 and has been associated with verbal memory deficits in older patients. These deficits are consistent with growing evidence that insulin contributes to the functioning of the hippocampus and adjoining medial temporal structures supporting memory. Furthermore, the hypothalamic-pituitary-adrenal (HPA) axis, commonly dysregulated in insulin resistant persons, interacts with the hippocampus and may influence memory. Therefore, IR may contribute to T2DM-related memory impairment. The proposed studies will examine the effects of improving IR on central nervous system (CNS) functions in T2DM and impaired glucose tolerance (IGT). Three hypotheses will be tested: that improving insulin sensitivity will (1) enhance memory and other cognitive functions, (2) increase cerebral glucose metabolism in the hippocampus and adjoining medial temporal structures, and (3) normalize cerebrospinal fluid (CSF) levels of insulin and the CSF-to-plasma insulin ratio. We will
Studies
15
also characterize the effects of improving IR on plasma and CSF levels of amyloid peptides, which are regulated in part by circulating insulin. In a Core Study, newly diagnosed persons with T2DM and IGT will be randomized to receive the insulin sensitizer rosiglitazone (4 mg bid), the insulin secretagogue nateglinide (120 mg tid), or placebo for 16 weeks. Cognitive measures and blood samples for neuroendocrine assays will be obtained at baseline, treatment weeks 8 and 16, and after 8 weeks of washout. It is predicted that both agents will enhance memory, and that rosiglitazone will produce a greater degree of enhancement than nateglinide. A subset of Core Study subjects will receive either positron emission tomography (PET) imaging or lumbar puncture (LP) to obtain CSF at baseline and treatment week 16. In addition, a healthy control group will receive only baseline PETs or LPs. Significant findings will provide converging evidence that JR can adversely influence various CNS functions and suggest that an important therapeutic goal in IGT and T2DM is to improve insulin sensitivity. Furthermore, results of these studies should point to new avenues of research, such as examination of the cellular effects of IR on cerebral glucose metabolism and their relationship to cognition. Finally, these studies have the potential to elucidate relationships between T2DM and other disorders in which memory is impaired, such as Alzheimer?s disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INSULIN SENSITIVITY IN PCOS--EFFECT OF ROSIGLITAZONE Principal Investigator & Institution: Henry, Robert R.; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 920930934 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: INSULIN/TZD REGULATION OF PROTEIN STRUCTURE IN FAT CELLS Principal Investigator & Institution: Schaufele, Fred J.; Metabolic Research Unit; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2003; Project Start 01-MAR-2003; Project End 28-FEB-2005 Summary: (provided by applicant): Diabetes results from deficiencies in insulin production and/or insulin signaling. Insulin signals adipocytes to alter the expression of genes for enzymes and hormones that regulate energy balance. Transcription factors that control the expression of these genes include peroxisome proliferator activated receptor gamma (PPARy) and CCAAT enhancer binding protein alpha (C/EBPa). Insulin signaling alters the phosphorylation status of C/EBPa. PPARy is the receptor for thiazolidenediones (TZDs). PPARy heterodimerizes with RXR, the receptor for 9-cis retinoic acid, which enhances the insulin-sensitizing actions of TZDs. The interactions of these factors with themselves, their ligands and co-activators in response to insulin are poorly defined. Understanding these interactions in the cellular milieu will lead to improved insulin-sensitizing therapies.We uniquely have developed powerful fluorescence microscopy techniques that measure the amounts, structure and interactions of proteins at tens of thousands of locations within cells. Transcription factors and co-factors involved in insulin regulation will be tagged with spectrally distinct derivatives of green fluorescent protein (GFP), and expressed pairwise in 3T3-L1 pre-adipocyte/adipocyte model cells. The relative locations of each factor will be determined microscopically within the living cell by comparing the locations of fluorescence emitted from each fluorophore-factor fusion. Factor location will be
16
Rosiglitazone
compared to gene location by in situ hybridizations in fixed cells. Direct interactions between, and conformations within, the factors will be measured at each subcellular location as the degree to which fluorescence energy excited in the fluorophore attached to one factor (or factor domain) is transferred to a fluorophore attached to the second factor (or domain). Thus, regulation of these cooperative factors will be determined, in 3T3-L1 cells, by measuring the separate and combined effects of insulin, the TZD rosiglitazone and 9-cis retinoic acid on the:1. location, dimerization and interactions of C/EBPa, PPARg, RXRa and their co-activators PGC-1, PGC-2, SRC-la, CBP and TRAP2202. conformation of C/EBPa, PPARg, RXRa and the same co-activators, and3. conformations, dimers and interactions of the above factors specifically in the neighborhood of the genes that they regulate. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INTERVENTIONS THAT RETARD MAMMALIAN AGING Principal Investigator & Institution: Harrison, David E.; Jackson Laboratory 600 Main St Bar Harbor, Me 04609 Timing: Fiscal Year 2003; Project Start 15-APR-2003; Project End 30-JUN-2008 Summary: (provided by applicant): Aging-associated debilitation is a primary source of human misery. Healthy life spans in mammalian models can be increased by dietary and genetic means; however, no effective intervention applicable to humans has yet been validated in mammals. Human trials for "anti-aging" treatments are unlikely to proceed without such validation, which is the purpose of this RFA. The following aims are designed to definitively identify effective anti-aging interventions and to rule out those that are ineffective. Aim 1: To verify that potential anti-aging interventions produce their expected biological effects. For anti-inflammatory agents (corticosterone, ibuprofin, celecoxib), insulin sensitizing agents (CL316,243, rosiglitazone), agents that promote mitochondrial function or suppress oxidative damage (R-alpha lipoic acid, Lcarnitine), and for multi-functional phytochemicals, the following will be determined: doses and modes of administration that produce biological effects, both short and long term, without toxicity or a decrease in food consumption. Aim 2: To test the hypotheses that potential anti-aging interventions in these three categories actually retard aging in biological systems and increase life spans. Noninvasive, longitudinal measures are made of growth, immune cells, insulin/glucose, collagen, healing and urine. Because aging is multifactorial, combinations of interventions proven in Aim 1 also will be tested. Aim 3: To confirm and augment the conclusions regarding interventions successful in the first phase of the program. Whether interventions that increase maximum life span also retard expression of aging in the following biological systems will be tested: Neurobehavorial/sensory, mitochondrial, gene expression and protein modification, followed by detailed histopathological analyses. Results in these systems may suggest mechanisms by which the interventions retard aging. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: MENTORED DEVELOPMENT AW
PATIENT
ORIENTED
RESEARCH
CAREER
Principal Investigator & Institution: Barry-Carr, Darcy; Obstetrics and Gynecology; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 01-AUG-2000; Project End 31-JUL-2005 Summary: PROPOSAL (Adapted from the applicant's abstract): Pre-eclampsia, a hypertensive disorder unique to pregnancy, is a leading cause of maternal and neonatal
Studies
17
morbidity and mortality. Endothelial dysfunction is a central feature in the pathophysiology of pre-eclampsia. Mechanisms that have been suggested to contribute to the endothelial dysfunction of pre-eclampsia include insulin resistance and a hyperdynamic circulation (high cardiac output). Insulin resistance and high cardiac output persist postpartum, suggesting that these women have an underlying disorder. However, it is unclear whether these abnormalities are related and whether insulin resistance has a role in producing hemodynamic alterations and endothelial dysfunction in these women. The investigator hypothesizes that postpartum women who have a history of pre- eclampsia are insulin resistant and have associated alterations in hemodynamics and endothelial function. Furthermore, she hypothesizes that insulin resistance has a causal role in producing these changes. Two specific aims have been identified to address these hypotheses: 1) to determine whether the insulin resistance present in postpartum women with a history of pre-eclampsia is associated with altered hemodynamics and endothelial dysfunction; and 2) to determine whether reversing insulin resistance in women with a history of pre-eclampsia, is associated with improvements in hemodynamics and endothelial function, thus suggesting that insulin resistance is a causative factor in women with these abnormalities. A case-control study will address the first specific aim. A double-blind, placebo-controlled, randomized study will address the second specific aim by using an insulin sensitizing agent, rosiglitazone, as an interventional tool. The results of these studies could provide a rationale for future investigations aimed at determining whether treating insulin resistance in women with a history of pre-eclampsia will decrease the risk of recurrent pre- eclampsia in subsequent pregnancies and reduce the prevalence of the long-term metabolic and cardiovascular complications in these women as they age. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NON-CLASSICAL PRODUCITON
EFFECTS
OF
TZDS
ON
CHEMOKINE
Principal Investigator & Institution: Schaefer, Katherine L.; Boston Medical Center Gambro Bldg, 2Nd Fl, 660 Harrison Ave, Ste a Boston, Ma 02118 Timing: Fiscal Year 2004; Project Start 01-MAR-2004; Project End 28-FEB-2007 Summary: (provided by applicant): Inflammatory bowel diseases (IBD) are characterized by episodes of intestinal inflammation. Recent evidence suggests that activation of a nuclear receptor, PPAR-gamma, with a synthetic TZD ligand, BRL, offers protection against inflammation, at least in part by regulating inflammatory chemokine production from intestinal epithelial cells, both at the transcriptional and posttranscriptional levels. Interestingly, the chemokine promoters do not have PPARgamma response elements, indicating that the activated PPAR-gamma, or possibly BRL itself, affect chemokine production in "non-classical" ways. In addition, BRL affects numerous rapid phosphorylation events after cellular stimulation, including many molecules involved in MAP kinase signaling. To test the hypothesis that activated PPAR-gamma or BRL itself regulate chemokine production by modulating MAP kinase signaling, the mechanisms of regulation of a representative chemokine, IP-10, will be determined. The effects of BRL on IP-10 regulation in the presence and absence of PPAR-gamma will be determined, and the signaling pathways affected by BRL delineated in detail. The results of these experiments will further understanding of the mechanism of action of synthetic PPAR-gamma ligands and help in the development of IBD therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
18
Rosiglitazone
•
Project Title: P450 PHENOTYPE AND CHEMOTHERAPY TOXICITY IN THE ELDERLY Principal Investigator & Institution: Dees, Elizabethh C.; Medicine; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2007 Summary: (provided by applicant): Interpatient variability in toxic and therapeutic response to chemotherapy remains a major problem in cancer treatment. The long-term goal of this work is to better understand the pharmacologic and pharmacogenetic determinants of this interpatient variability so as to individualize chemotherapy to maximize benefit and minimize toxicity. This is particularly important in older cancer patients, a group that has routinely been excluded from treatment or empirically dosereduced. The central hypothesis of this research plan is that an individual's activity, or phenotype, of relevant drug metabolizing enzymes, which can be determined at the bedside using carefully selected metabolic "probes," can predict that patient's pharmacokinetics (PK) for certain chemotherapy. Further, the results of these probebased tests can be incorporated into models to better tailor dosing. The enzymes targeted in this proposal are the cytochromes P450 (CYPs), particularly the enzyme families CYP2 and CYP3, which represent the major pathways for oxidative metabolism of drugs in the liver. There is large interpatient variation in CYP activity. There are known genetic polymorphisms in many CYPs, but CYP genotype and phenotype may not correlate well in patients with cancer. In addition, age-related decline in CYP expression may be a key factor in increased toxicity in this age group. Probe-based tests that assay CYP phenotype have been developed for some of these enzymes but not for others This proposal examines the value of probe tests of CYP activity in predicting pharmacokinetics and toxicity of paclitaxel and vinorelbine. Paclitaxel is principally metabolized by CYP2C8 and CYP3A4, and vinorelbine by CYP3A4. The first trial is a dose escalation study of weekly paclitaxel administered on a novel schedule, which is targeted toward older patients with lung or breast cancer. Detailed pharmacokinetic parameters will be correlated with toxicity. In the second phase of the trial, CYP3A4 activity will be measured using the erythromycin breath test (ERMBT), and a novel probe-based assay for CYP2C8 (rosiglitazone) will be pilot tested. Drug metabolism phenotype will be correlated with paclitaxel clearance and toxicity, and a predictive model will be designed and prospectively validated in future studies. CYP2C8 and CYP3A4 genotype-phenotype correlations will also be explored. In the second clinical trial, age-related decline in CYP3A4 activity and its impact on clearance and neutropenia in patients treated with vinorelbine will be evaluated. Again, predictive models will be designed and genotype-phenotype correlations explored. The research projects described form the core of a five-year career development plan for Dr. Elizabeth Dees, an Assistant Professor in the Division of Hematology/Oncology. Her mentor, Dr. Paul Watkins, is a leader in the field of pharmacogenetics and drug metabolism and is the Director of the GCRC. Co-mentor, Dr. Beverly Mitchell, is the applicant's Division Director and is the Associate Director of Lineberger Comprehensive Cancer Center (LCCC). They propose a combined didactic and clinical research experience utilizing the resources of the LCCC to foster Dr. Dees's development into an independent clinician investigator with expertise in pharmacokinetics and phenotyping drug metabolizing enzymes. They have assembled a carefully selected group of collaborators and advisors to assist in the research projects and Dr. Dees's career development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
Studies
•
19
Project Title: PHARMACOGENETICS OF PRO12ALA PPAR GAMMA 2 IN DIABETES Principal Investigator & Institution: Shuldiner, Alan R.; Professor; Medicine; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-AUG-2004 Summary: (Verbatim from Applicant's Abstract): Clinical studies indicate that there is great variability in the ability of thiazolidinediones, a class of insulin-sensitizing agents, to improve glycemic control in patients with type 2 diabetes. The receptor for thiazolidinediones is peroxisome proliferator activated receptor-gamma (PPARgama), a nuclear receptor that plays an important role in adipogenesis and insulin signaling. We recently identified a common genetic variant in the PPARgamma gene (Pro12Ala PPARgamma2). In vitro studies indicate that this single amino acid substitution has functional consequences. Furthermore, Pro12Ala PPARgamma2 is associated with increased body mass index (BMI) in two Caucasian populations, increased insulin sensitivity in African Americans and Pima Indians, and more rapid weight regain after weight loss in postmenopausal Caucasian women. We hypothesize that inter-individual variability in therapeutic efficacy to thiazolidinediones is due, at least in part, to genetic factors. Specifically, we hypothesize that diabetic subjects who carry the Pro12Ala PPARgamma2 variant will be more insulin sensitive and therefore less responsive to the insulin-sensitizing and glucose lowering effects of rosiglitazone therapy as compared to subjects without the variant. To test this hypothesis, we will perform a prospective rosiglitazone intervention in subjects with type 2 diabetes who either carry or lack the Pro12Ala PPARgamma2 variant. We will compare between the two groups responsivity to rosiglitazone therapy as measured by changes in glycemic control (hemoglobin A1c, fasting blood glucose), lipoprotein profile, insulin sensitivity (euglycemic hyperinsulinemic clamp), and fat metabolism (lipolysis by microdialysis and fat oxidation by indirect calorimetry. Furthermore, to detect novel genes and pathways that predict rosiglitazone responsivity and/or influence insulin sensitivity, we will compare between rosiglitazone responders and nonresponders mRNA expression patterns of several thousand genes in muscle and adipose tissue biopsies using cDNA microarray technology. These studies will define the clinical significance of the Pro12Ala PPARgamma2 variant, and the role of PPARgamma in adipocyte metabolism and insulin signaling in humans more generally. Testing for the Pro12Ala PPARgamma2 may differentiate between patients who will be responsive or unresponsive to thiazolidinedione therapy, which would allow physicians to more rationally prescribe medications based on underlying genetic mechanisms. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: PPAR GAMMA AGONISTS FOR THE PREVENTION OF COLON CANCER Principal Investigator & Institution: Wargovich, Michael J.; Professor; Pathology and Microbiology; University of South Carolina at Columbia Byrnes Bldg., Room 501 Columbia, Sc 29208 Timing: Fiscal Year 2002; Project Start 05-JAN-2001; Project End 31-DEC-2003 Summary: Epidemiological studies strongly associate non-steroidal anti- inflammatory drug (NSAID) use with reduced risk for colon cancer. NSAIDS prevent colon cancer. However, alternative explanations may exist. Certain NSAIDS are ligands for peroxisome proliferator-activated receptors (PPARs), members of the nuclear receptor superfamily of transcription factors. The overall investigating agonists of PPAR gamma
20
Rosiglitazone
as possible chemopreventives for colon cancer. Colon cancer is the second cancer. The hypothesis to be tested is that agonists of PPAR gamma, a form of PPAR highly expressed in the colon epithelium and colon tumors, will be chemopreventive for he colon. I propose two aims to test the hypothesis, protein expression in rat colon epithelium. Effects on normal and colon carcinogen-treated rodent colon will be explored. We will test troglitazone, pioglitazone, rosiglitazone, BRL 49653 and the antiinflammatory NSAIDs, indomethacin and ibuprofen. Results from these studies will provide a direct link between the reportedly elevated expression levels of PPAR gamma in the colon and compounds that activate it. In Aim 2, we will determine in the rat colon using inhibition of aberrant crypt foci (ACF) as an intermediate endpoint. These studies are aimed at determining whether PPAR gamma agonists are inhibitors of tumorigenesis in vivo. Secondary studies will assess the effects of these compounds on colonic cell proliferation and apoptotic rates. These studies will define PPAR gamma as a possible target for chemopreventive drug development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PPAR-GAMMA AS TARGET OF PROSTATE CANCER THERAPY Principal Investigator & Institution: Spiegelman, Bruce M.; Professor; Dana-Farber Cancer Institute 44 Binney St Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 19-SEP-2002; Project End 30-APR-2007 Summary: (provided by applicant): The nuclear receptor PPAR gamma is a dominant regulator of adipose differentiation and a modulator of the growth of many cell types. It is activated by synthetic ligands including the synthetic thiazolidinedione (TZD) drugs, such as rosiglitazone. Recent data, from our lab and others, indicates that PPAR gamma activation can inhibit the growth of epithelial cells from prostate, breast and colon, and change patterns of gene expression toward a more differentiated phenotype. Small clinical trials in human prostate cancer have shown that rosiglitazone can cause a prolonged stabilization in PSA levels in a subset of human patients. This has led to an additional, larger clinical trial; this project is intended to help support and advance the planning and interpretation of human clinical trials for the use of PPAR gamma ligands in CaP. Our first Aim will perform transcriptional profiling in human CaP cells treated with PPAR gamma ligands. We will pay particular attention to genes, which encode cell surface or secreted proteins, as these could serve to measure PPAR gamma activation. Our second Aim will study the genetic status of the PPAR gamma gene in the patients in the DF/HCC clinical trials. In particular, it will be important to correlate responsiveness in the patients with expression levels and potential mutations or deletions in PPAR gamma. Our final Aim will perform experiments in mice that will model the treatment of CaP with PPAR gamma ligands. We will first examine the effects of PPAR gamma, mutations on the propensity toward CaP in mice with mutations in PTEN and P21. These mice will then be used to examine the effects of a PPAR gamma ligand (rosiglitazone) before and during the development of cancer. These studies together will provide useful knowledge that may eventually lead to new methods to prevent or treat human CaP. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: PPAR-GAMMA NUCLEAR TRANSCRIPTION FACTOR: A NOVEL TARGET FOR LEUKEMIA THERAPY Principal Investigator & Institution: Andreeff, Michael W.; Stringer Professor for Cancer Treatment; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030
Studies
21
Timing: Fiscal Year 2003; Project Start 05-AUG-2003; Project End 30-APR-2008 Summary: New approaches are needed to improve cure rates in adult hematological malignancies. PPARgamma (Peroxisome Proliferator-Activated Receptor Gamma) is a member of the nuclear transcription factor family involved in signaling of differentiation. We have demonstrated that PPARgamma is expressed in the majority of primary human leukemias but not in normal hematopoietic progenitors, and that ligation of PPARgamma induces differentiation, growth arrest and apoptosis in leukemias. We propose to extend our initial studies on the mechanisms and efficacy of PPARgamma signaling in acute myeloid leukemia to acute and chronic (CLL) leukemia, with the goal of developing PPARgamma as a novel target for the treatment of hematological malignancies. We are encouraged to pursue this goal by the seminal impact on leukemia therapy that was affected by targeting RARalpha in acute promyelocytic leukemia (APL) with ATRA. First, we will investigate the expression of PPARgamma, in acute and chronic myeloid and lymphoid human leukemias and leukemic stem cells and study the effects of PPARgamma ligands on apoptosis and differentiation. We will determine the effects of combined targeting of PPARgamma and RXR in leukemias, as PPARgamma, and RXR heterodimerization is required to maximize transcriptional activation. In the second aim, we will further elucidate the specific mechanisms of apoptotic cell death and growth arrest that are triggered by PPARgamma, ligation. Preliminary data demonstrate that PPARgamma ligands induce loss of mitochondrial membrane potential and activation of effector caspases. Finally, we propose to initiate Phase I studies using PPARgamma ligands, in combination with rexinoids. These studies will utilize FDA approved PPARgamma and RXR ligands and the new potent triterpenoid CDDO, a novel PPARgamma, ligand that is presently being developed by us with assistance from CTEP/RAID at the National Cancer Institute. The long-term goal of the proposed studies is to determine the molecular, biological and clinical effects of PPARgamma/RXR ligation in human leukemia and to develop the PPARgamma/RXR nuclear receptor system as a novel target for leukemia therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PREVENTION OF BREAST CANCER-TARGETING COX-2 & PPARGAMMA Principal Investigator & Institution: Badawi, Alaa F.; Assistant Member; Fox Chase Cancer Center Philadelphia, Pa 19111 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2004 Summary: (provided by applicant) The continuing magnitude of breast cancer with respect to incidence and mortality and the limited options for treatment provide a strong rationale for identifying new, selective molecular targets for prevention of this malignancy. Recently, cyclooxygenase-2 (COX-2) and peroxisome proliferator-activated receptors-y (PPARgamma) have been characterized as holding great promise for breast cancer chemoprevention. Both molecules regulate important biological processes and may play a role in breast carcinogenesis. Induction of COX-2 and inactivation of PPARgamma occur in this malignant disease and it appears that they contribute to cancer induction either directly or via their coordinate effects on a wide array of cancerrelated genes and transcription factors. Our studies and those of others indicate that inhibition of COX-2 or activation of PPARY prevents mammary carcinomas in rodents. Combinational chemoprevention, whereby synergism can be achieved between two drugs, represents an important advancement in the field of cancer prevention. Our preliminary observation indicates that targeting COX-2 and PPARgamma can synergistically inhibit the proliferation of human breast cancer cells. Taken together, we
22
Rosiglitazone
hypothesize that simultaneous targeting of COX-2 and PPARy may inhibit the development of mammary gland carcinoma to an extent superior to that produced by targeting either of these two regulatory molecules alone. Further, we believe that COX-2 inhibitors and PPARy-agonists may act via a common pathway(s) or mechanism(s) of action through which they influence the expression of a wide array of genes and transcription factors and, thereby, elicit their cancer preventive effects. To test our hypothesis, we plan to accomplish the following specific aims: Aim 1: to determine the chemopreventive efficacy of a COX-2 selective inhibitor (celecoxib) and a PPARyagonist (rosiglitazone) when administered in combination on the N-methyl-Nnitrosourea-induced rat mammary gland carcinogenesis during initiation and postinitiation stages. Aim 2: to elucidate the mechanistic action of celecoxib and rosiglitazone on chemoprevention by identifying target genes and transcription factors modulated in the mammary epithelial cells of rats treated with both agents at various time intervals, using CDNA microarray analyses. This pilot preclinical study introduces a novel strategy for breast cancer prevention. Results of this study may enable us to: i) deten-nine the significance of simultaneous targeting of COX-2 and PPARgamma, ii) identify mechanisms by which COX-2 inhibitors and PPARy-ligands elicit their cancer preventive effects, and iii) evaluate the applicability of this approach of the prevention of human breast cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PROTEASE INHIBITOR RELATED ADIPOGENESIS IN HIV INFECTION Principal Investigator & Institution: Agrawal, Krishna C.; Regents Professor and Chairperson; Pharmacology; Tulane University of Louisiana New Orleans, La New Orleans, La 70112 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 31-MAY-2004 Summary: (Provided by applicant) The clinical use of HIV-1 protease inhibitors (PIs) in highly active anti-retroviral therapy (HART) has led to significant improvements in the prognosis and quality of life in HIV-1 infected patients. However, long-term use of PIs has resulted in side effects such as peripheral lipodystrophy, hyperlipidemia, insulin resistance, and disruption of the adipogenic process. Our preliminary studies have shown that PIs suppress adipogenic differentiation in 3T3-L1 cells and the addition of TNFalpha further suppressed the rate of adipogenesis. In contrast, the insulin sensitizing agent, troglitazone, blocked this suppression even in TNFalpha sensitized cells. The primary goal of the proposed research is to investigate the molecular mechanisms involved in the PI-induced modulation of adipogenesis and to test the hypothesis that preadipocytes are sensitized by HIV-1 induced inflammatory cytokine TNFalpha and/or HIV-1 Tat protein, to PI-induced disruption of adipogenesis. This will be achieved by the following specific aims: 1.) To determine the in vitro effects of PIs on adipogenic differentiation in human bone marrow stromal progenitor cells. Transcripts of early, middle and late genetic markers i.e., pref-1, lipoprotein lipase (LPL) and GAPDH, respectively will be determined. Levels of nuclear transcription factors, PPARgamma and C/EBP-alpha will be determined by transient transfection assays and gel mobility shift assays. 2.) to determine the sensitizing effect of the HIV-1 induced inflammatory cytokine, TNFalpha and/or HIV-1 Tat protein on PI-induced inhibition of adipogenic differentiation in human bone marrow stromal progenitor cells. 3.) To determine the in vitro effects of PIs on the activity of ECM degrading proteases in human stromal adipogenic progenitor cells. Fibrinolytic activity in undifferentiated and differentiated cells will be monitored by using a chromogenic plasmin substrate. The
Studies
23
ECM production at different stages of differentiation will be determined by SDS-PAGE electrophoresis and the activation of ECM degrading proteolytic enzymes (MMPs) will be monitored by gelatin zymography. Real time RT-PCR studies will monitor gene expression of tPA, PAI-1/2 and MMPs/TIMPs which are involved in the fibrinolytic cascade. 4.) To investigate the ameliorative effects of insulin sensitizers on PI-induced lipodystrophy. We will investigate the efficacy of thiazolidinediones (rosiglitazone and pioglitazone) and biguanides (metformin) in suppressing the effects of PI-induced inhibition of adipogenic differentiation. These studies will delineate the molecular mechanisms that may be responsible for the adipogenic side effects induced by the PIs in the presence of HIV infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RANDOMIZED TRIAL OF ROSIGLITAZONE FOR ULCERATIVE COLITIS Principal Investigator & Institution: Lewis, James D.; Assistant Professor; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant): Ulcerative colitis (UC) is a chronic inflammatory disease involving all or a portion of the colon. Currently, there are few effective medical therapies for UC. Furthermore, because of the potential toxicity of the currently available agents, there is a great need for alternative therapies to treat patients with UC refractory to therapy with 5-ASA agents. Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of transcription factors whose activities are regulated by high affinity binding of small lipophilic ligands such as steroid hormones. A new class of diabetic drugs, the thiazolidinediones, has been developed to bind to the gamma (g) subtype of the PPARs. Colonic epithelial cells express high levels of PPARg protein and have the ability to produce inflammatory cytokines that may contribute to the inflammatory process in UC. We have previously demonstrated that PPARg ligands significantly attenuate cytokine gene expression related to the inflammatory cascade in colon cancer cell lines. Furthermore, we and others have demonstrated that thiazolidinedione ligands for PPARg markedly reduce colonic inflammation in murine models of ulcerative colitis. In addition, we have shown in a pilot study that more than 50% of patients with mild to moderately active UC despite therapy with 5-ASA agents (and corticosteroids or imunomodulator medications for most patients) experienced improved symptoms within 12 weeks of therapy with rosiglitazone 4 mg twice daily. As such, we believe that PPARg may represent a novel target for modulating colonic inflammation in UC. The proposed study is a multi-center, double-blind, randomized controlled trial of rosiglitazone versus placebo for mild to moderately active ulcerative colitis refractory to standard therapy with oral 5-ASA agents. 176 subjects will be randomized to rosiglitazone 4mg bid or placebo for 12 weeks of therapy. The primary outcome will be improvement in disease activity as measured by the Disease Activity Index first described by Sutherland. Secondary outcomes will include clinical remission and quality of life. We will use the techniques of immunohistochemistry to detect expression of PPARg receptors in human colon tissue. We will also use the technique of immunohistochemistry to examine the change in NF-KB activation prior to and following therapy with either placebo or rosiglitazone. Specifically, we will compare expression of p65 and phosphorylated IKB-alpha, in colonic tissue prior to and following exposure to rosiglitazone and placebo. If our hypothesis is correct, this study will serve to establish that ligands for PPARg possess
24
Rosiglitazone
biological activity necessary to modulate the inflammatory response in the intact human colon. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RENAL ANGIOTENSIN LL RECEPTOR FUNCTION IN OBESITY Principal Investigator & Institution: Hussain, Tahir; Pharmacological and Pharmaceutical Sciences; University of Houston 4800 Calhoun Rd Houston, Tx 77004 Timing: Fiscal Year 2003; Project Start 15-MAR-2003; Project End 31-JAN-2008 Summary: (provided by applicant): Recently, we have observed that blockade of AT1 receptors causes greater diuresis and natriuresis in obese than in lean Zucker rats. Additionally, in vitro experiments demonstrate an increase in the AT1 receptor number on brush border membranes and a greater stimulation of the proximal tubule Na/H exchanger and Na,K-ATPase activity by Ang II in obese compared to lean rats. Furthermore, pretreatment of proximal tubule epithelial cells (OK cells) with insulin caused a potentiation of the Ang II-mediated stimulation of Na/K-ATPase and Na/Hexchanger and an increase in AT1 receptor expression. Collectively, these results lead us to hypothesize that Ang II increases tubular sodium and water reabsorption and contributes to hypertension in obese Zucker rats via an enhanced AT1 receptor signaling due to AT1 receptor up-regulation; and that the AT1 receptor up-regulation is caused by hyperinsulinemia, a characteristic of obese Zucker rats. To test this hypothesis we will quantify the AT1 receptor expression on proximal tubule plasma membranes using ligand binding, AT1mRNA contents/rate of transcription in proximal tubules, and examine the AT1 receptor signaling in lean and obese rats. To understand the role of hyperinsulinemia on the AT1 receptor up-regulation, obese rats will be treated with rosiglitazone/streptozotocin to lower the levels of plasma insulin or lean rats will be treated with exogenous insulin to produce hyperinsulinemia. The AT1 receptor number, signaling and function on sodium reabsorption will be studied in these treated rats. The exaggerated natriuretic response following AT1 receptor blockade in obese rats could also indicate exaggerated AT2 receptor signaling. Therefore, additional experiments are designed to determine the role of AT2 receptors on sodium excretion and determine the abundance of AT2 receptors. The proposed study will provide the molecular mechanism of AT1 receptor up-regulation and the enhanced AT1 receptor signaling. From a therapeutic perspective, it will also allow us to establish whether lowering of the plasma insulin levels leads to the restoration of the AT1 receptors function to normal levels and reduces blood pressure in obese rats. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: ROSIGLITAZONE IN POLYCYSTIC OVARY SYNDROME Principal Investigator & Institution: Cataldo, Nicholas A.; Assistant Professor of Obstetrics and Gy; Gynecology and Obstetrics; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2005 Summary: (Adapted from applicant's description): Polycystic ovary syndrome (PCOS) is a disorder affecting about 5% of reproductive-age women characterized by anovulation and excess production of androgens by the ovary. Anovulation causes menstrual irregularity and infertility, while excess androgens cause unwanted hair growth and may promote acne. Traditional treatments for PCOS have consisted of medication to stimulate ovulation if fertility is desired, or medication to suppress or block androgents or restore regular menstrual cycles if fertility is not an immediate goal, but these treatments are often mutually exclusive PCOS is frequently associated with a common
Studies
25
metabolic disorder, insulin resistance, and like insulin resistance alone carries an increased risk of non-reproductive health problems such as the development of diabetes or atherosclerosis. Insulin resistance leads to excessive insulin secretion, and this may stimulate the ovary to hypersecrete androgens. In the last few years, published reports have described the treatment of PCOS with insulin sensitizers, medications developed to treat diabetes which can improve insulin resistance. These drugs can improve the hormonal abnormalities in PCOS and in some cases can restore regular menses and/or ovulation. Of the two marketed drugs tested to date, metformin has not been consistently effective, while troglitazone is effective but has been found to have an unacceptable risk of liver toxicity. This project will study rosiglitazone, a newly approved drug closely related to troglitazone in structure and action but without apparent toxicity, in an open-label, Phase II format. Subjects with PCOS wiII have insulin resistance identified by dynamic testing using the octreotide insulin suppression test, and after further evaluation of provoked insulin secretion will receive rosiglitazone daily in one of three doses for 12 weeks. Insulin resistance and insulin secretion, glucose tolerance, serum total and free testosterone, LH, and circulating lipids will be measured on rosiglitazone and compared to subjects' pretreatment values. The occurrence of ovulation will be evaluated by weekly serum progesterone levels. The dose of rosiglitazone and the time needed for its effect to develop will be determined. Associations between effects on metabolic parameters and effects on reproductive ones will be sought. The hypothesis of this study is that rosiglitazone can improve insulin sensitivity and lower circulating insulin, and thereby restore ovulation as well as correct elevated LH and testosterone. Rosiglitazone is potentially an appropriate and beneficial treatment for all women with PCOS and insulin resistance regardless of goals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SKELETAL MUSCLE--NEW BODY COMPOSITION MODELS //METHODS Principal Investigator & Institution: Heymsfield, Steve; St. Luke's-Roosevelt Inst for Hlth Scis Health Sciences New York, Ny 10019 Timing: Fiscal Year 2002 Summary: The proposed studies are prompted by subcutaneous adipose tissue (SAT) wasting and visceral adipose tissue VAT) accumulation, plus hyperlipidemia and insulin resistance (R1) observed in HIV-infected patients receiving highly active antiretroviral therapies. There is concern that these developments promote atherosclerosis. However, it is not clear how the body composition changes are related to the metabolic changes, which fat compartments affect RI, nor if the risks are the same in HIV and nonHIV conditions. The underlying hypothesis is that aspects of HIV infection or its treatment decrease the influence of VAT upon RI. The specific aims are, 1) To determine the effects of HIV infection upon the relationship between body fat distribution and R1; 2) To compare the effects of diet plus exercise upon fat distribution and RI in HIVinfected and uninfected women with increased VAT; 3) To compare the effects of a thiazolidinedione, rosiglitazone, upon VAT and R1 in HIV-infected and uninfected men with increased VAT. In preliminary studies, we described the phenotypic changes that occur in HIV-infected subjects, distinguished true from pseudotruncal obesity, demonstrated the influence of sex, and determined the effects of treatment with growth hormone and resistance exercise upon VAT. We also have described the effects of race, age and total fat mass upon the relationship between VAT and R1 in non-HIV infected women, assessed possible contributions of upper body SAT to RI, and made measurements of glucose disposal rate and endogenous glucose production. A total of
26
Rosiglitazone
180 studies are planned for PPG III. Cross sectional studies will determine the effect of HIV infection upon fat distribution and RI over a wide range of VAT, while the intervention studies will be performed in subgroups of subjects with increased VAT. Studies will include composition analysis by whole body MRI, including estimation of intramyocellular lipid, and other body composition techniques, and studies of RI by euglycemic clamp technique. Safety analyses as well as other PPG III endpoints, such as quality of life, also be measured. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THIAZOLIDINEDIONE-INDUCED HEPATOTOXICITY Principal Investigator & Institution: Harvison, Peter J.; Associate Professor; Pharmaceutical Sciences; University of the Sciences Philadelphia in Philadelphia Philadelphia, Pa 19104 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2006 Summary: (provided by applicant): Various agricultural, industrial, and pharmaceutical agents contain 2,4-thiazolidinedione (TZD) rings. For example, a TZD ring is found in the insulin-sensitizing agents, troglitazone, rosiglitazone and pioglitazone, which have been or are used in the treatment of type II diabetes. Although the toxicology of the TZD ring has not been extensively investigated, troglitazone was removed from the market after it was associated with over 70 cases of hepatotoxicity that required transplants or resulted in deaths. There have also been reports of liver injuries in patients taking rosiglitazone and pioglitazone. The mechanism by which these drugs damage the liver is not known, although metabolism in the TZD ring may be a factor. Unfortunately, there are no reliable animal models to investigate this process. Recently, 3-(3,5dichlorophenyl)-2,4- thiazolidinedione (DCPT) was found to reproducibly cause liver damage in rats. Since this compound also contains a TZD ring, it is conceivable the presence of this structural feature may be critical for the production of hepatotoxicity. Therefore, DCPT may be a useful model compound to investigate TZD ring-induced liver damage in a commonly used laboratory animal species. In analogy to the insulinsensitizing agents, it is also conceivable that DCPT must undergo metabolism before liver damage will occur. The current proposal is designed to examine the hypothesis that biotransformation in the TZD ring contributes to the hepatotoxicity of DCPT in rats. This hypothesis will be tested through the following Specific Aims: (1) investigate the effect of structural modification on DCPT-induced liver damage in rats to determine if the TZD ring is essential for liver damage; (2) examine of the effect of metabolic enzyme activity modulation on DCPT-induced hepatotoxicity in rats to establish if metabolism in the TZD ring is required for hepatotoxicity; and (3) investigate the potential formation of reactive intermediates from DCPT in vitro, in an effort to elucidate the nature of any putative toxic metabolites that may be generated via biotransformation. The reproducible liver damage that DCPT causes in an animal model may provide a unique opportunity to investigate the potential participation of the TZD ring in liver damage. Since people are exposed to TZD ring-containing compounds, this work may form the basis for future studies about TZD ring-induced hepatotoxicity in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
Studies
27
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 “rosiglitazone” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for rosiglitazone in the PubMed Central database: •
Mitochondrial Biogenesis and Remodeling during Adipogenesis and in Response to the Insulin Sensitizer Rosiglitazone. by Wilson-Fritch L, Burkart A, Bell G, Mendelson K, Leszyk J, Nicoloro S, Czech M, Corvera S.; 2003 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=140688
•
Rosiglitazone (Avandia) and pioglitazone (Actos) and heart failure. by Wooltorton E.; 2002 Jan 22; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=99278
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 rosiglitazone, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “rosiglitazone” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for rosiglitazone (hyperlinks lead to article summaries):
3 4
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. 6 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.
28
Rosiglitazone
•
A comparison of the effects of rosiglitazone and glyburide on cardiovascular function and glycemic control in patients with type 2 diabetes. Author(s): St John Sutton M, Rendell M, Dandona P, Dole JF, Murphy K, Patwardhan R, Patel J, Freed M. Source: Diabetes Care. 2002 November; 25(11): 2058-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12401757
•
A comprehensive review of the antidiabetic agent rosiglitazone. Author(s): Glazer NB, Cheatham WW. Source: Clinical Therapeutics. 2001 February; 23(2): 307-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11293563
•
A diabetes outcome progression trial (ADOPT): an international multicenter study of the comparative efficacy of rosiglitazone, glyburide, and metformin in recently diagnosed type 2 diabetes. Author(s): Viberti G, Kahn SE, Greene DA, Herman WH, Zinman B, Holman RR, Haffner SM, Levy D, Lachin JM, Berry RA, Heise MA, Jones NP, Freed MI. Source: Diabetes Care. 2002 October; 25(10): 1737-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12351470
•
A phase II trial with rosiglitazone in liposarcoma patients. Author(s): Debrock G, Vanhentenrijk V, Sciot R, Debiec-Rychter M, Oyen R, Van Oosterom A. Source: British Journal of Cancer. 2003 October 20; 89(8): 1409-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14562008
•
A prospective, randomized comparison of the metabolic effects of pioglitazone or rosiglitazone in patients with type 2 diabetes who were previously treated with troglitazone. Author(s): Khan MA, St Peter JV, Xue JL. Source: Diabetes Care. 2002 April; 25(4): 708-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11919129
•
A randomized trial of rosiglitazone therapy in patients with inadequately controlled insulin-treated type 2 diabetes. Author(s): Raskin P, Rendell M, Riddle MC, Dole JF, Freed MI, Rosenstock J; Rosiglitazone Clinical Trials Study Group. Source: Diabetes Care. 2001 July; 24(7): 1226-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11423507
Studies
29
•
A review of rosiglitazone in type 2 diabetes mellitus. Author(s): Werner AL, Travaglini MT. Source: Pharmacotherapy. 2001 September; 21(9): 1082-99. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11560198
•
Absorption, disposition, and metabolism of rosiglitazone, a potent thiazolidinedione insulin sensitizer, in humans. Author(s): Cox PJ, Ryan DA, Hollis FJ, Harris AM, Miller AK, Vousden M, Cowley H. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2000 July; 28(7): 772-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10859151
•
Accelerated hypertension due to rosiglitazone therapy. Author(s): Vikram NK, Misra A, Devi JR. Source: Indian Heart J. 2002 November-December; 54(6): 733. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12674195
•
Activation of protein kinase C-zeta by insulin and phosphatidylinositol-3,4,5-(PO4)3 is defective in muscle in type 2 diabetes and impaired glucose tolerance: amelioration by rosiglitazone and exercise. Author(s): Beeson M, Sajan MP, Dizon M, Grebenev D, Gomez-Daspet J, Miura A, Kanoh Y, Powe J, Bandyopadhyay G, Standaert ML, Farese RV. Source: Diabetes. 2003 August; 52(8): 1926-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12882907
•
Addition of biphasic insulin aspart 30 to rosiglitazone in type 2 diabetes mellitus that is poorly controlled with glibenclamide monotherapy. Author(s): Raz I, Mouritzen U, Vaz J, Hershkovitz T, Wainstein J, Harman-Boehm I. Source: Clinical Therapeutics. 2003 December; 25(12): 3109-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14749149
•
Addition of low-dose rosiglitazone to sulphonylurea therapy improves glycaemic control in Type 2 diabetic patients. Author(s): Wolffenbuttel BH, Gomis R, Squatrito S, Jones NP, Patwardhan RN. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 2000 January; 17(1): 40-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10691158
•
Addition of nateglinide to rosiglitazone monotherapy suppresses mealtime hyperglycemia and improves overall glycemic control. Author(s): Fonseca V, Grunberger G, Gupta S, Shen S, Foley JE. Source: Diabetes Care. 2003 June; 26(6): 1685-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12766094
30
Rosiglitazone
•
Addition of rosiglitazone to existing sulfonylurea treatment in chinese patients with type 2 diabetes and exposure to hepatitis B or C. Author(s): Zhu XX, Pan CY, Li GW, Shi HL, Tian H, Yang WY, Jiang J, Sun XC, Davies C, Chow WH. Source: Diabetes Technology & Therapeutics. 2003; 5(1): 33-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12725705
•
Addition of rosiglitazone to metformin is most effective in obese, insulin-resistant patients with type 2 diabetes. Author(s): Jones TA, Sautter M, Van Gaal LF, Jones NP. Source: Diabetes, Obesity & Metabolism. 2003 May; 5(3): 163-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12681023
•
An international study of the effects of rosiglitazone plus sulphonylurea in patients with type 2 diabetes. Author(s): Vongthavaravat V, Wajchenberg BL, Waitman JN, Quimpo JA, Menon PS, Ben Khalifa F, Chow WH; 125 Study Group. Source: Current Medical Research and Opinion. 2002; 18(8): 456-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12564655
•
An open-label trial of the PPAR-gamma ligand rosiglitazone for active ulcerative colitis. Author(s): Lewis JD, Lichtenstein GR, Stein RB, Deren JJ, Judge TA, Fogt F, Furth EE, Demissie EJ, Hurd LB, Su CG, Keilbaugh SA, Lazar MA, Wu GD. Source: The American Journal of Gastroenterology. 2001 December; 96(12): 3323-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11774944
•
Antidiabetic PPAR gamma-activator rosiglitazone reduces MMP-9 serum levels in type 2 diabetic patients with coronary artery disease. Author(s): Marx N, Froehlich J, Siam L, Ittner J, Wierse G, Schmidt A, Scharnagl H, Hombach V, Koenig W. Source: Arteriosclerosis, Thrombosis, and Vascular Biology. 2003 February 1; 23(2): 2838. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12588772
•
Are the metabolic effects of rosiglitazone influenced by baseline glycaemic control? Author(s): Goldstein BJ, Cobitz AR, Hand LM, Chen H. Source: Current Medical Research and Opinion. 2003; 19(3): 192-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12803733
Studies
31
•
Automated high-performance liquid chromatography method for the determination of rosiglitazone in human plasma. Author(s): Muxlow AM, Fowles S, Russell P. Source: J Chromatogr B Biomed Sci Appl. 2001 March 5; 752(1): 77-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11254200
•
Characterization of the cytochrome P450 enzymes involved in the in vitro metabolism of rosiglitazone. Author(s): Baldwin SJ, Clarke SE, Chenery RJ. Source: British Journal of Clinical Pharmacology. 1999 September; 48(3): 424-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10510156
•
Complementary mode of action of rosiglitazone and metformin in a single tablet for the treatment of diabetes mellitus type 2. Author(s): Petersen KU. Source: Arzneimittel-Forschung. 2004; 54(1): 20-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14979605
•
Conversion from troglitazone to rosiglitazone. Author(s): Bell DS, Ovalle F, Shadmany S. Source: Endocrine Practice : Official Journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2001 July-August; 7(4): 326. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11497487
•
Correction of insulin resistance and hyperandrogenism in polycystic ovary syndrome by combined rosiglitazone and clomiphene citrate therapy. Author(s): Shobokshi A, Shaarawy M. Source: Journal of the Society for Gynecologic Investigation. 2003 February; 10(2): 99104. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12593999
•
Crossover and double blind study with metformin and rosiglitazone in impaired glucose tolerance subjects. Author(s): Flores-Saenz JL, Trujillo-Arriaga HM, Rivas-Vilchis JF, Mendez-Francisco JD, Alarcon-Aguilar FJ, Roman-Ramos R. Source: Proc West Pharmacol Soc. 2003; 46: 143-7. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14699913
•
Differences in lipid profiles of patients given rosiglitazone followed by pioglitazone. Author(s): LaCivita KA, Villarreal G. Source: Current Medical Research and Opinion. 2002; 18(6): 363-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12442884
32
Rosiglitazone
•
Differential activation of peroxisome proliferator-activated receptor-gamma by troglitazone and rosiglitazone. Author(s): Camp HS, Li O, Wise SC, Hong YH, Frankowski CL, Shen X, Vanbogelen R, Leff T. Source: Diabetes. 2000 April; 49(4): 539-47. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10871190
•
Differential effects of rosiglitazone and metformin on adipose tissue distribution and glucose uptake in type 2 diabetic subjects. Author(s): Virtanen KA, Hallsten K, Parkkola R, Janatuinen T, Lonnqvist F, Viljanen T, Ronnemaa T, Knuuti J, Huupponen R, Lonnroth P, Nuutila P. Source: Diabetes. 2003 February; 52(2): 283-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12540598
•
Differential in vitro hepatotoxicity of troglitazone and rosiglitazone among cryopreserved human hepatocytes from 37 donors. Author(s): Lloyd S, Hayden MJ, Sakai Y, Fackett A, Silber PM, Hewitt NJ, Li AP. Source: Chemico-Biological Interactions. 2002 November 10; 142(1-2): 57-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12399155
•
Differential regulation of adiponectin secretion from cultured human omental and subcutaneous adipocytes: effects of insulin and rosiglitazone. Author(s): Motoshima H, Wu X, Sinha MK, Hardy VE, Rosato EL, Barbot DJ, Rosato FE, Goldstein BJ. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 December; 87(12): 5662-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12466369
•
Differential regulation of lipogenesis and leptin production by independent signaling pathways and rosiglitazone during human adipocyte differentiation. Author(s): Patel NG, Holder JC, Smith SA, Kumar S, Eggo MC. Source: Diabetes. 2003 January; 52(1): 43-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12502492
•
Differential vasoactive effects of the insulin sensitizers rosiglitazone (BRL 49653) and troglitazone on human small arteries in vitro. Author(s): Walker AB, Naderali EK, Chattington PD, Buckingham RE, Williams G. Source: Diabetes. 1998 May; 47(5): 810-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9588454
Studies
33
•
Effect of metformin and rosiglitazone combination therapy in patients with type 2 diabetes mellitus: a randomized controlled trial. Author(s): Fonseca V, Rosenstock J, Patwardhan R, Salzman A. Source: Jama : the Journal of the American Medical Association. 2000 April 5; 283(13): 1695-702. Erratum In: Jama 2000 September 20; 284(11): 1384. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10755495
•
Effect of rifampin on the pharmacokinetics of rosiglitazone in healthy subjects. Author(s): Park JY, Kim KA, Kang MH, Kim SL, Shin JG. Source: Clinical Pharmacology and Therapeutics. 2004 March; 75(3): 157-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15001966
•
Effect of rosiglitazone on glucose and non-esterified fatty acid metabolism in Type II diabetic patients. Author(s): Miyazaki Y, Glass L, Triplitt C, Matsuda M, Cusi K, Mahankali A, Mahankali S, Mandarino LJ, DeFronzo RA. Source: Diabetologia. 2001 December; 44(12): 2210-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11793023
•
Effect of rosiglitazone on spontaneous and clomiphene citrate-induced ovulation in women with polycystic ovary syndrome. Author(s): Ghazeeri G, Kutteh WH, Bryer-Ash M, Haas D, Ke RW. Source: Fertility and Sterility. 2003 March; 79(3): 562-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12620440
•
Effect of rosiglitazone treatment on nontraditional markers of cardiovascular disease in patients with type 2 diabetes mellitus. Author(s): Tuepker J. Source: Circulation. 2003 April 29; 107(16): E109; Author Reply E109. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12719295
•
Effect of rosiglitazone treatment on nontraditional markers of cardiovascular disease in patients with type 2 diabetes mellitus. Author(s): Haffner SM, Greenberg AS, Weston WM, Chen H, Williams K, Freed MI. Source: Circulation. 2002 August 6; 106(6): 679-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12163427
•
Effect of rosiglitazone treatment on soluble CD40L in patients with type 2 diabetes and coronary artery disease. Author(s): Marx N, Imhof A, Froehlich J, Siam L, Ittner J, Wierse G, Schmidt A, Maerz W, Hombach V, Koenig W. Source: Circulation. 2003 April 22; 107(15): 1954-7. Epub 2003 Apr 14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12695287
34
Rosiglitazone
•
Effects of metformin and rosiglitazone monotherapy on insulin-mediated hepatic glucose uptake and their relation to visceral fat in type 2 diabetes. Author(s): Iozzo P, Hallsten K, Oikonen V, Virtanen KA, Parkkola R, Kemppainen J, Solin O, Lonnqvist F, Ferrannini E, Knuuti J, Nuutila P. Source: Diabetes Care. 2003 July; 26(7): 2069-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12832315
•
Effects of pioglitazone and rosiglitazone on blood lipid levels and glycemic control in patients with type 2 diabetes mellitus: a retrospective review of randomly selected medical records. Author(s): Boyle PJ, King AB, Olansky L, Marchetti A, Lau H, Magar R, Martin J. Source: Clinical Therapeutics. 2002 March; 24(3): 378-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11952022
•
Effects of rosiglitazone alone and in combination with atorvastatin on the metabolic abnormalities in type 2 diabetes mellitus. Author(s): Freed MI, Ratner R, Marcovina SM, Kreider MM, Biswas N, Cohen BR, Brunzell JD; Rosiglitazone Study 108 investigators. Source: The American Journal of Cardiology. 2002 November 1; 90(9): 947-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12398960
•
Effects of rosiglitazone and linoleic acid on human preadipocyte differentiation. Author(s): Hutley LJ, Newell FM, Joyner JM, Suchting SJ, Herington AC, Cameron DP, Prins JB. Source: European Journal of Clinical Investigation. 2003 July; 33(7): 574-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12814394
•
Effects of rosiglitazone maleate when added to a sulfonylurea regimen in patients with type 2 diabetes mellitus and mild to moderate renal impairment: a post hoc analysis. Author(s): Agrawal A, Sautter MC, Jones NP. Source: Clinical Therapeutics. 2003 November; 25(11): 2754-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14693302
•
Effects of rosiglitazone on endothelial function, C-reactive protein, and components of the metabolic syndrome in nondiabetic patients with the metabolic syndrome. Author(s): Wang TD, Chen WJ, Lin JW, Chen MF, Lee YT. Source: The American Journal of Cardiology. 2004 February 1; 93(3): 362-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14759393
Studies
35
•
Efffect of addition of low-dose rosiglitazone to sulphonylurea therapy on glycemic control in type 2 diabetic patients. Author(s): Yang J, Di F, He R, Zhu X, Wang D, Yang M, Wang Y, Yuan S, Chen J. Source: Chinese Medical Journal. 2003 May; 116(5): 785-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12875702
•
Efficacy and safety of rosiglitazone plus metformin in Mexicans with type 2 diabetes. Author(s): Gomez-Perez FJ, Fanghanel-Salmon G, Antonio Barbosa J, Montes-Villarreal J, Berry RA, Warsi G, Gould EM. Source: Diabetes/Metabolism Research and Reviews. 2002 March-April; 18(2): 127-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11994904
•
Evaluation of liver function in type 2 diabetic patients during clinical trials: evidence that rosiglitazone does not cause hepatic dysfunction. Author(s): Lebovitz HE, Kreider M, Freed MI. Source: Diabetes Care. 2002 May; 25(5): 815-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11978674
•
Failure to develop hepatic injury from rosiglitazone in a patient with a history of troglitazone-induced hepatitis. Author(s): Lenhard MJ, Funk WB. Source: Diabetes Care. 2001 January; 24(1): 168-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11194222
•
Gemfibrozil considerably increases the plasma concentrations of rosiglitazone. Author(s): Niemi M, Backman JT, Granfors M, Laitila J, Neuvonen M, Neuvonen PJ. Source: Diabetologia. 2003 October; 46(10): 1319-23. Epub 2003 July 29. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12898007
•
Glycemic control with glyburide/metformin tablets in combination with rosiglitazone in patients with type 2 diabetes: a randomized, double-blind trial. Author(s): Dailey GE 3rd, Noor MA, Park JS, Bruce S, Fiedorek FT. Source: The American Journal of Medicine. 2004 February 15; 116(4): 223-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14969649
•
Guidance on rosiglitazone for type 2 diabetes mellitus. Author(s): Matthews DR. Source: Lancet. 2001 February 10; 357(9254): 481. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11273100
36
Rosiglitazone
•
Hepatic failure in a patient taking rosiglitazone. Author(s): Forman LM, Simmons DA, Diamond RH. Source: Annals of Internal Medicine. 2000 January 18; 132(2): 118-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10644272
•
Hepatocellular injury in a patient receiving rosiglitazone. A case report. Author(s): Al-Salman J, Arjomand H, Kemp DG, Mittal M. Source: Annals of Internal Medicine. 2000 January 18; 132(2): 121-4. Erratum In: Ann Intern Med 2000 August 1; 133(3): 237. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10644273
•
HPLC method for the determination of rosiglitazone in human plasma and its application in a clinical pharmacokinetic study. Author(s): Mamidi RN, Chaluvadi MR, Benjamin B, Ramesh M, Katneni K, Babu AP, Bhanduri J, Rao NM, Rajagopalan R. Source: Arzneimittel-Forschung. 2002; 52(7): 560-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12189780
•
Identification of high-affinity binding sites for the insulin sensitizer rosiglitazone (BRL-49653) in rodent and human adipocytes using a radioiodinated ligand for peroxisomal proliferator-activated receptor gamma. Author(s): Young PW, Buckle DR, Cantello BC, Chapman H, Clapham JC, Coyle PJ, Haigh D, Hindley RM, Holder JC, Kallender H, Latter AJ, Lawrie KW, Mossakowska D, Murphy GJ, Roxbee Cox L, Smith SA. Source: The Journal of Pharmacology and Experimental Therapeutics. 1998 February; 284(2): 751-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9454824
•
Improved insulin sensitivity and body fat distribution in HIV-infected patients treated with rosiglitazone: a pilot study. Author(s): Gelato MC, Mynarcik DC, Quick JL, Steigbigel RT, Fuhrer J, Brathwaite CE, Brebbia JS, Wax MR, McNurlan MA. Source: Journal of Acquired Immune Deficiency Syndromes (1999). 2002 October 1; 31(2): 163-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12394794
•
Improved nonalcoholic steatohepatitis after 48 weeks of treatment with the PPARgamma ligand rosiglitazone. Author(s): Neuschwander-Tetri BA, Brunt EM, Wehmeier KR, Oliver D, Bacon BR. Source: Hepatology (Baltimore, Md.). 2003 October; 38(4): 1008-17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14512888
Studies
37
•
Improvement in insulin sensitivity followed by ovulation and pregnancy in a woman with polycystic ovary syndrome who was treated with rosiglitazone. Author(s): Cataldo NA, Abbasi F, McLaughlin TL, Lamendola C, Reaven GM. Source: Fertility and Sterility. 2001 November; 76(5): 1057-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11704136
•
Improvement of acquired partial lipodystrophy with rosiglitazone despite ongoing complement activation. Author(s): Walker UA, Kirschfink M, Peter HH. Source: Rheumatology (Oxford, England). 2003 February; 42(2): 393-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12595651
•
In vitro inhibitory effects of troglitazone and its metabolites on drug oxidation activities of human cytochrome P450 enzymes: comparison with pioglitazone and rosiglitazone. Author(s): Yamazaki H, Suzuki M, Tane K, Shimada N, Nakajima M, Yokoi T. Source: Xenobiotica; the Fate of Foreign Compounds in Biological Systems. 2000 January; 30(1): 61-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10659951
•
Influence of rosiglitazone treatment on beta-cell function in type 2 diabetes: evidence of an increased ability of glucose to entrain high-frequency insulin pulsatility. Author(s): Juhl CB, Hollingdal M, Porksen N, Prange A, Lonnqvist F, Schmitz O. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 August; 88(8): 3794-800. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12915671
•
Insulin and rosiglitazone regulation of lipolysis and lipogenesis in human adipose tissue in vitro. Author(s): McTernan PG, Harte AL, Anderson LA, Green A, Smith SA, Holder JC, Barnett AH, Eggo MC, Kumar S. Source: Diabetes. 2002 May; 51(5): 1493-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11978647
•
Insulin-sensitising drugs (metformin, troglitazone, rosiglitazone, pioglitazone, Dchiro-inositol) for polycystic ovary syndrome. Author(s): Lord JM, Flight IH, Norman RJ. Source: Cochrane Database Syst Rev. 2003; (3): Cd003053. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12917943
38
Rosiglitazone
•
Interim results of a pilot study demonstrating the early effects of the PPAR-gamma ligand rosiglitazone on insulin sensitivity, aminotransferases, hepatic steatosis and body weight in patients with non-alcoholic steatohepatitis. Author(s): Neuschwander-Tetri BA, Brunt EM, Wehmeier KR, Sponseller CA, Hampton K, Bacon BR. Source: Journal of Hepatology. 2003 April; 38(4): 434-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12663234
•
Isolated elevation of alkaline phosphatase level associated with rosiglitazone. Author(s): Hachey DM, O'Neil MP, Force RW. Source: Annals of Internal Medicine. 2000 November 7; 133(9): 752. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11074926
•
Lack of effect of rosiglitazone on the pharmacokinetics of oral contraceptives in healthy female volunteers. Author(s): Inglis AM, Miller AK, Culkin KT, Finnerty D, Patterson SD, Jorkasky DK, Freed MI. Source: Journal of Clinical Pharmacology. 2001 June; 41(6): 683-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11402638
•
Lack of effect of sucralfate on the absorption and pharmacokinetics of rosiglitazone. Author(s): Rao MN, Mullangi R, Katneni K, Ravikanth B, Babu AP, Rani UP, Naidu MU, Srinivas NR, Rajagopalan R. Source: Journal of Clinical Pharmacology. 2002 June; 42(6): 670-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12043956
•
Liquid chromatographic method for the determination of rosiglitazone in human plasma. Author(s): Kolte BL, Raut BB, Deo AA, Bagool MA, Shinde DB. Source: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences. 2003 May 5; 788(1): 37-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12668069
•
Liver failure in a patient treated with long-term rosiglitazone therapy. Author(s): Gouda HE, Khan A, Schwartz J, Cohen RI. Source: The American Journal of Medicine. 2001 November; 111(7): 584-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11705443
•
Management of rosiglitazone-induced edema: two case reports and a review of the literature. Author(s): Wang F, Aleksunes LM, Reagan LA, Vergara CM. Source: Diabetes Technology & Therapeutics. 2002; 4(4): 505-14. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12396745
Studies
39
•
No effect of rosiglitazone for treatment of HIV-1 lipoatrophy: randomised, doubleblind, placebo-controlled trial. Author(s): Carr A, Workman C, Carey D, Rogers G, Martin A, Baker D, Wand H, Law M, Samaras K, Emery S, Cooper DA; Rosey investigators. Source: Lancet. 2004 February 7; 363(9407): 429-38. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14962523
•
Novel genes regulated by the insulin sensitizer rosiglitazone during adipocyte differentiation. Author(s): Albrektsen T, Frederiksen KS, Holmes WE, Boel E, Taylor K, Fleckner J. Source: Diabetes. 2002 April; 51(4): 1042-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11916924
•
Once- and twice-daily dosing with rosiglitazone improves glycemic control in patients with type 2 diabetes. Author(s): Phillips LS, Grunberger G, Miller E, Patwardhan R, Rappaport EB, Salzman A; Rosiglitazone Clinical Trials Study Group. Source: Diabetes Care. 2001 February; 24(2): 308-15. Erratum In: Diabetes Care 2001 May; 24(5): 973. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11213884
•
Peroxisome proliferator-activated receptor-gamma represses GLUT4 promoter activity in primary adipocytes, and rosiglitazone alleviates this effect. Author(s): Armoni M, Kritz N, Harel C, Bar-Yoseph F, Chen H, Quon MJ, Karnieli E. Source: The Journal of Biological Chemistry. 2003 August 15; 278(33): 30614-23. Epub 2003 May 29. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12777391
•
Pharmacokinetics of rosiglitazone in patients with end-stage renal disease. Author(s): Thompson-Culkin K, Zussman B, Miller AK, Freed MI. Source: J Int Med Res. 2002 July-August; 30(4): 391-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12235921
•
Pharmacokinetics of rosiglitazone in patients with varying degrees of renal insufficiency. Author(s): Chapelsky MC, Thompson-Culkin K, Miller AK, Sack M, Blum R, Freed MI. Source: Journal of Clinical Pharmacology. 2003 March; 43(3): 252-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12638393
40
Rosiglitazone
•
Possible heart failure exacerbation associated with rosiglitazone: case report and literature review. Author(s): Page RL 2nd, Gozansky WS, Ruscin JM. Source: Pharmacotherapy. 2003 July; 23(7): 945-54. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12885108
•
PPAR gamma agonists in type 2 diabetes: how far have we come in 'preventing the inevitable'? A review of the metabolic effects of rosiglitazone. Author(s): Zinman B. Source: Diabetes, Obesity & Metabolism. 2001 August; 3 Suppl 1: S34-43. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11685828
•
PPAR gamma-dependent anti-inflammatory action of rosiglitazone in human monocytes: suppression of TNF alpha secretion is not mediated by PTEN regulation. Author(s): Hong G, Davis B, Khatoon N, Baker SF, Brown J. Source: Biochemical and Biophysical Research Communications. 2003 April 11; 303(3): 782-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12670479
•
Pulmonary edema associated with rosiglitazone and troglitazone. Author(s): Thomas ML, Lloyd SJ. Source: The Annals of Pharmacotherapy. 2001 January; 35(1): 123-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11197573
•
Reduced production rates of testosterone and dihydrotestosterone in healthy men treated with rosiglitazone. Author(s): Vierhapper H, Nowotny P, Waldhausl W. Source: Metabolism: Clinical and Experimental. 2003 February; 52(2): 230-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12601638
•
Regulation of gene expression by activation of the peroxisome proliferator-activated receptor gamma with rosiglitazone (BRL 49653) in human adipocytes. Author(s): Rieusset J, Auwerx J, Vidal H. Source: Biochemical and Biophysical Research Communications. 1999 November; 265(1): 265-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10548525
Studies
41
•
Regulation of plasma PAI-1 concentrations in HAART-associated lipodystrophy during rosiglitazone therapy. Author(s): Yki-Jarvinen H, Sutinen J, Silveira A, Korsheninnikova E, Fisher RM, Kannisto K, Ehrenborg E, Eriksson P, Hamsten A. Source: Arteriosclerosis, Thrombosis, and Vascular Biology. 2003 April 1; 23(4): 688-94. Epub 2003 February 20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12615670
•
Resistin and type 2 diabetes: regulation of resistin expression by insulin and rosiglitazone and the effects of recombinant resistin on lipid and glucose metabolism in human differentiated adipocytes. Author(s): McTernan PG, Fisher FM, Valsamakis G, Chetty R, Harte A, McTernan CL, Clark PM, Smith SA, Barnett AH, Kumar S. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 December; 88(12): 6098-106. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14671216
•
Response to treatment with rosiglitazone in familial partial lipodystrophy due to a mutation in the LMNA gene. Author(s): Owen KR, Donohoe M, Ellard S, Hattersley AT. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 2003 October; 20(10): 823-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14510863
•
Rosiglitazone (Avandia) and pioglitazone (Actos) and heart failure. Author(s): Wooltorton E. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2002 January 22; 166(2): 219. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11826947
•
Rosiglitazone (Avandia): hepatic, cardiac and hematological reactions. Author(s): McMorran M, Vu D. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2001 July 10; 165(1): 82-3, 86-7. English, French. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11468963
•
Rosiglitazone amplifies the benefits of lifestyle intervention measures in longstanding type 2 diabetes mellitus. Author(s): Reynolds LR, Konz EC, Frederich RC, Anderson JW. Source: Diabetes, Obesity & Metabolism. 2002 July; 4(4): 270-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12099976
42
Rosiglitazone
•
Rosiglitazone and hepatic failure. Author(s): Freid J, Everitt D, Boscia J. Source: Annals of Internal Medicine. 2000 January 18; 132(2): 164. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10644281
•
Rosiglitazone and liver failure. Author(s): Isley WL, Oki JC. Source: Annals of Internal Medicine. 2000 September 5; 133(5): 393-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10979889
•
Rosiglitazone and pulmonary oedema: an acute dose-dependent effect on human endothelial cell permeability. Author(s): Idris I, Gray S, Donnelly R. Source: Diabetologia. 2003 February; 46(2): 288-90. Epub 2003 February 12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12627329
•
Rosiglitazone and type 2 diabetes mellitus. Author(s): Bragg T. Source: Lancet. 2001 May 5; 357(9266): 1451. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11360960
•
Rosiglitazone approved for treatment of type 2 diabetes. Author(s): Miller JL. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 1999 July 1; 56(13): 1292, 1294. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10683120
•
Rosiglitazone but not metformin enhances insulin- and exercise-stimulated skeletal muscle glucose uptake in patients with newly diagnosed type 2 diabetes. Author(s): Hallsten K, Virtanen KA, Lonnqvist F, Sipila H, Oksanen A, Viljanen T, Ronnemaa T, Viikari J, Knuuti J, Nuutila P. Source: Diabetes. 2002 December; 51(12): 3479-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12453903
•
Rosiglitazone does not affect the steady-state pharmacokinetics of digoxin. Author(s): Di Cicco RA, Miller AK, Patterson S, Freed MI. Source: Journal of Clinical Pharmacology. 2000 December; 40(12 Pt 2): 1516-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11185675
Studies
43
•
Rosiglitazone does not alter the pharmacokinetics of metformin. Author(s): Di Cicco RA, Allen A, Carr A, Fowles S, Jorkasky DK, Freed MI. Source: Journal of Clinical Pharmacology. 2000 November; 40(11): 1280-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11075314
•
Rosiglitazone has no clinically significant effect on nifedipine pharmacokinetics. Author(s): Harris RZ, Inglis AM, Miller AK, Thompson KA, Finnerty D, Patterson S, Jorkasky DK, Freed MI. Source: Journal of Clinical Pharmacology. 1999 November; 39(11): 1189-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10579151
•
Rosiglitazone improves downstream insulin receptor signaling in type 2 diabetic patients. Author(s): Miyazaki Y, He H, Mandarino LJ, DeFronzo RA. Source: Diabetes. 2003 August; 52(8): 1943-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12882909
•
Rosiglitazone improves glucose metabolism in nondiabetic uremic patients on CAPD. Author(s): Lin SH, Lin YF, Kuo SW, Hsu YJ, Hung YJ. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 2003 October; 42(4): 774-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14520628
•
Rosiglitazone improves insulin sensitivity and lowers blood pressure in hypertensive patients. Author(s): Raji A, Seely EW, Bekins SA, Williams GH, Simonson DC. Source: Diabetes Care. 2003 January; 26(1): 172-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12502676
•
Rosiglitazone in combination with glimepiride plus metformin in type 2 diabetic patients. Author(s): Kiayias JA, Vlachou ED, Theodosopoulou E, Lakka-Papadodima E. Source: Diabetes Care. 2002 July; 25(7): 1251-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12087036
•
Rosiglitazone in the management of older patients with type 2 diabetes mellitus. Author(s): Kreider M, Heise M. Source: Int J Clin Pract. 2002 September; 56(7): 538-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12296617
44
Rosiglitazone
•
Rosiglitazone in the treatment of HAART-associated lipodystrophy--a randomized double-blind placebo-controlled study. Author(s): Sutinen J, Hakkinen AM, Westerbacka J, Seppala-Lindroos A, Vehkavaara S, Halavaara J, Jarvinen A, Ristola M, Yki-Jarvinen H. Source: Antivir Ther. 2003 June; 8(3): 199-207. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12924536
•
Rosiglitazone in the treatment of type 2 diabetes mellitus: a critical review. Author(s): Malinowski JM, Bolesta S. Source: Clinical Therapeutics. 2000 October; 22(10): 1151-68; Discussion 1149-50. Review. Erratum In: Clin Ther 2001 February; 23(2): 309. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11110228
•
Rosiglitazone in Type 2 diabetes mellitus: an evaluation in British Indo-Asian patients. Author(s): Barnett AH, Grant PJ, Hitman GA, Mather H, Pawa M, Robertson L, Trelfa A; Indo-Asian Trial Investigators. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 2003 May; 20(5): 387-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12752488
•
Rosiglitazone inhibits proliferation, motility, and matrix metalloproteinase production in keratinocytes. Author(s): Bhagavathula N, Nerusu KC, Lal A, Ellis CN, Chittiboyina A, Avery MA, Ho CI, Benson SC, Pershadsingh HA, Kurtz TW, Varani J. Source: The Journal of Investigative Dermatology. 2004 January; 122(1): 130-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14962101
•
Rosiglitazone inhibits the insulin-mediated increase in PAI-1 secretion in human abdominal subcutaneous adipocytes. Author(s): Harte AL, McTernan PG, McTernan CL, Smith SA, Barnett AH, Kumar S. Source: Diabetes, Obesity & Metabolism. 2003 September; 5(5): 302-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12940867
•
Rosiglitazone monotherapy and type 2 diabetes. Author(s): Lawrence IG. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 2001 November; 18 Suppl 4: 6-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11989215
Studies
45
•
Rosiglitazone monotherapy improves glycaemic control in patients with type 2 diabetes: a twelve-week, randomized, placebo-controlled study. Author(s): Patel J, Anderson RJ, Rappaport EB. Source: Diabetes, Obesity & Metabolism. 1999 May; 1(3): 165-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11220295
•
Rosiglitazone monotherapy is effective in patients with type 2 diabetes. Author(s): Lebovitz HE, Dole JF, Patwardhan R, Rappaport EB, Freed MI; Rosiglitazone Clinical Trials Study Group. Source: The Journal of Clinical Endocrinology and Metabolism. 2001 January; 86(1): 2808. Erratum In: J Clin Endocrinol Metab 2001 April; 86(4): 1659. J Clin Endocrinol Metab. 2002 February; 2(1): Iv. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11232013
•
Rosiglitazone prevents the impairment of human islet function induced by fatty acids: evidence for a role of PPARgamma2 in the modulation of insulin secretion. Author(s): Lupi R, Del Guerra S, Marselli L, Bugliani M, Boggi U, Mosca F, Marchetti P, Del Prato S. Source: American Journal of Physiology. Endocrinology and Metabolism. 2004 April; 286(4): E560-7. Epub 2003 November 18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14625208
•
Rosiglitazone reduces blood pressure and urinary albumin excretion in type 2 diabetes: G Bakris et al. Author(s): Grossman E. Source: Journal of Human Hypertension. 2003 January; 17(1): 5-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12571610
•
Rosiglitazone reduces urinary albumin excretion in type II diabetes. Author(s): Bakris G, Viberti G, Weston WM, Heise M, Porter LE, Freed MI. Source: Journal of Human Hypertension. 2003 January; 17(1): 7-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12571611
•
Rosiglitazone short-term monotherapy lowers fasting and post-prandial glucose in patients with type II diabetes. Author(s): Raskin P, Rappaport EB, Cole ST, Yan Y, Patwardhan R, Freed MI. Source: Diabetologia. 2000 March; 43(3): 278-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10768088
46
Rosiglitazone
•
Rosiglitazone taken once daily provides effective glycaemic control in patients with Type 2 diabetes mellitus. Author(s): Nolan JJ, Jones NP, Patwardhan R, Deacon LF. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 2000 April; 17(4): 287-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10821295
•
Rosiglitazone toxicity. Author(s): Ravinuthala RS, Nori U. Source: Annals of Internal Medicine. 2000 October 17; 133(8): 658. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11033603
•
Rosiglitazone treatment increases nitric oxide production in human peripheral skin: a controlled clinical trial in patients with type 2 diabetes mellitus. Author(s): Vinik AI, Stansberry KB, Barlow PM. Source: Journal of Diabetes and Its Complications. 2003 September-October; 17(5): 27985. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12954157
•
Rosiglitazone treatment of patients with extreme insulin resistance and diabetes mellitus due to insulin receptor mutations has no effects on glucose and lipid metabolism. Author(s): Vestergaard H, Lund S, Pedersen O. Source: Journal of Internal Medicine. 2001 November; 250(5): 406-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11887975
•
Rosiglitazone, an agonist of peroxisome-proliferator-activated receptor gamma (PPARgamma), decreases inhibitory serine phosphorylation of IRS1 in vitro and in vivo. Author(s): Jiang G, Dallas-Yang Q, Biswas S, Li Z, Zhang BB. Source: The Biochemical Journal. 2004 January 15; 377(Pt 2): 339-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14556646
•
Rosiglitazone. Author(s): Wolffenbuttel BH, Sels JP, Huijberts MS. Source: Expert Opinion on Pharmacotherapy. 2001 March; 2(3): 467-78. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11336599
•
Rosiglitazone. Author(s): Goldstein BJ. Source: Int J Clin Pract. 2000 June; 54(5): 333-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10954962
Studies
47
•
Rosiglitazone. Author(s): Balfour JA, Plosker GL. Source: Drugs. 1999 June; 57(6): 921-30; Discussion 931-2. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10400405
•
Rosiglitazone: a review of its use in the management of type 2 diabetes mellitus. Author(s): Wagstaff AJ, Goa KL. Source: Drugs. 2002; 62(12): 1805-37. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12149047
•
Rosiglitazone: an agent from the thiazolidinedione class for the treatment of type 2 diabetes. Author(s): Cheng-Lai A, Levine A. Source: Heart Disease. 2000 July-August; 2(4): 326-33. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11728276
•
Rosiglitazone: potential beneficial impact on cardiovascular disease. Author(s): Viberti GC. Source: Int J Clin Pract. 2003 March; 57(2): 128-34. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12661797
•
Rosiglitazone-induced granulomatous hepatitis. Author(s): Dhawan M, Agrawal R, Ravi J, Gulati S, Silverman J, Nathan G, Raab S, Brodmerkel G Jr. Source: Journal of Clinical Gastroenterology. 2002 May-June; 34(5): 582-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11960075
•
Rosiglitazone--useful drug but has side effects. Author(s): Vidhya S, Mohan V. Source: J Assoc Physicians India. 2002 April; 50: 615. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12164432
•
Severe cholestatic hepatitis caused by thiazolidinediones: risks associated with substituting rosiglitazone for troglitazone. Author(s): Bonkovsky HL, Azar R, Bird S, Szabo G, Banner B. Source: Digestive Diseases and Sciences. 2002 July; 47(7): 1632-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12141828
48
Rosiglitazone
•
Synthetic peroxisome proliferator-activated receptor-gamma agonist, rosiglitazone, increases plasma levels of adiponectin in type 2 diabetic patients. Author(s): Yang WS, Jeng CY, Wu TJ, Tanaka S, Funahashi T, Matsuzawa Y, Wang JP, Chen CL, Tai TY, Chuang LM. Source: Diabetes Care. 2002 February; 25(2): 376-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11815513
•
Systemic exposure to rosiglitazone is unaltered by food. Author(s): Freed MI, Allen A, Jorkasky DK, DiCicco RA. Source: European Journal of Clinical Pharmacology. 1999 March; 55(1): 53-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10206085
•
The "glitazones": rosiglitazone and pioglitazone. Author(s): Papoushek C. Source: J Obstet Gynaecol Can. 2003 October; 25(10): 853-7. Review. Erratum In: J Obstet Gynaecol Can. 2003 November; 25(11): 907. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14532954
•
The effect of acarbose on the pharmacokinetics of rosiglitazone. Author(s): Miller AK, Inglis AM, Culkin KT, Jorkasky DK, Freed MI. Source: European Journal of Clinical Pharmacology. 2001 May; 57(2): 105-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11417440
•
The effect of ranitidine on the pharmacokinetics of rosiglitazone in healthy adult male volunteers. Author(s): Miller AK, DiCicco RA, Freed MI. Source: Clinical Therapeutics. 2002 July; 24(7): 1062-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12182252
•
The effect of rosiglitazone on serum lipoprotein(a) levels in Korean patients with type 2 diabetes mellitus. Author(s): Ko SH, Song KH, Ahn YB, Yoo SJ, Son HS, Yoon KH, Cha BY, Lee KW, Son HY, Kang SK. Source: Metabolism: Clinical and Experimental. 2003 June; 52(6): 731-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12800099
•
The effects of rosiglitazone on insulin sensitivity, lipolysis, and hepatic and skeletal muscle triglyceride content in patients with type 2 diabetes. Author(s): Mayerson AB, Hundal RS, Dufour S, Lebon V, Befroy D, Cline GW, Enocksson S, Inzucchi SE, Shulman GI, Petersen KF. Source: Diabetes. 2002 March; 51(3): 797-802. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11872682
Studies
49
•
The effects of rosiglitazone, a peroxisome proliferator-activated receptor-gamma agonist, on markers of endothelial cell activation, C-reactive protein, and fibrinogen levels in non-diabetic coronary artery disease patients. Author(s): Sidhu JS, Cowan D, Kaski JC. Source: Journal of the American College of Cardiology. 2003 November 19; 42(10): 175763. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14642684
•
The failings of NICE. NICE's guidance suggests using rosiglitazone in type 2 diabetes later than is ideal. Author(s): Robinson S, Valabhji J, Schachter M. Source: Bmj (Clinical Research Ed.). 2001 February 24; 322(7284): 491. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11222431
•
Troglitazone but not rosiglitazone induces G1 cell cycle arrest and apoptosis in human and rat hepatoma cell lines. Author(s): Bae MA, Rhee H, Song BJ. Source: Toxicology Letters. 2003 March 20; 139(1): 67-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12595159
•
Using thiazolidinediones: rosiglitazone and pioglitazone in clinical practice. Author(s): Peters AL. Source: Am J Manag Care. 2001 April; 7(3 Suppl): S87-95; Quiz S96-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11310177
51
CHAPTER 2. NUTRITION AND ROSIGLITAZONE Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and rosiglitazone.
Finding Nutrition Studies on Rosiglitazone 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 “rosiglitazone” (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.
52
Rosiglitazone
The following information is typical of that found when using the “Full IBIDS Database” to search for “rosiglitazone” (or a synonym): •
A prospective, randomized comparison of the metabolic effects of pioglitazone or rosiglitazone in patients with type 2 diabetes who were previously treated with troglitazone. Author(s): Division of Endocrinology, Mayo Clinic, Rochester, Minnesota, USA. Source: Khan, Mehmood A St Peter, John V Xue, Jay L Diabetes-Care. 2002 April; 25(4): 708-11 0149-5992
•
A randomized trial of rosiglitazone therapy in patients with inadequately controlled insulin-treated type 2 diabetes. Author(s): University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA.
[email protected] Source: Raskin, P Rendell, M Riddle, M C Dole, J F Freed, M I Rosenstock, J DiabetesCare. 2001 July; 24(7): 1226-32 0149-5992
•
Characterization of the cytochrome P450 enzymes involved in the in vitro metabolism of rosiglitazone. Author(s): Department of Drug Metabolism and Pharmacokinetics, SmithKline Beecham Pharmaceuticals, The Frythe, Welwyn, AL6 9AR, UK. Source: Baldwin, S J Clarke, S E Chenery, R J Br-J-Clin-Pharmacol. 1999 September; 48(3): 424-32 0306-5251
•
Differential regulation of lipogenesis and leptin production by independent signaling pathways and rosiglitazone during human adipocyte differentiation. Author(s): Division of Medical Sciences, University of Birmingham, Birmingham, U.K. Source: Patel, N G Holder, J C Smith, S A KuMarch, S Eggo, M C Diabetes. 2003 January; 52(1): 43-50 0012-1797
•
Effect of rosiglitazone on glucose and non-esterified fatty acid metabolism in Type II diabetic patients. Author(s): Diabetes Division, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA. Source: Miyazaki, Y Glass, L Triplitt, C Matsuda, M Cusi, K Mahankali, A Mahankali, S Mandarino, L J DeFronzo, R A Diabetologia. 2001 December; 44(12): 2210-9 0012-186X
•
Effects of rosiglitazone alone and in combination with atorvastatin on the metabolic abnormalities in type 2 diabetes mellitus. Author(s): GlaxoSmithKline, Collegeville, Pennsylvania 19426, USA.
[email protected] Source: Freed, M I Ratner, R Marcovina, S M Kreider, M M Biswas, N Cohen, B R Brunzell, J D Am-J-Cardiol. 2002 November 1; 90(9): 947-52 0002-9149
•
Fenofibrate and rosiglitazone lower serum triglycerides with opposing effects on body weight. Source: Chaput, E. Saladin, R. Silvestre, M. Edgar, A.D. Biochem-biophys-res-commun. Orlando, Fla. : Academic Press. May 10, 2000. volume 271 (2) page 445-450. 0006-291X
•
Hepatic failure in a patient taking rosiglitazone. Author(s): Division of Gastroenterology, Hospital of the University of Pennsylvania, Philadelphia 19104, USA. Source: Forman, L M Simmons, D A Diamond, R H Ann-Intern-Med. 2000 January 18; 132(2): 118-21 0003-4819
•
Insulin-sensitizing action of rosiglitazone is enhanced by preventing hyperphagia. Author(s): Department of Medicine, University of Liverpool, Liverpool, UK.
Nutrition 53
Source: Pickavance, L C Buckingham, R E Wilding, J P Diabetes-Obes-Metab. 2001 June; 3(3): 171-80 1462-8902 •
Lack of effect of rosiglitazone on the pharmacokinetics of oral contraceptives in healthy female volunteers. Author(s): SmithKline Beecham Pharmaceuticals, Clinical Pharmacology Unit, 51 N. 39th Street, Philadelphia, PA 19104, USA. Source: Inglis, A M Miller, A K Culkin, K T Finnerty, D Patterson, S D Jorkasky, D K Freed, M I J-Clin-Pharmacol. 2001 June; 41(6): 683-90 0091-2700
•
Lack of effect of sucralfate on the absorption and pharmacokinetics of rosiglitazone. Author(s): Bioanalysis, Drug Metabolism, and Pharmacokinetics, Dr. Reddy's Research Foundation, Ameerpet, Hyderabad, India. Source: Rao, M N Mullangi, R Katneni, K Ravikanth, B Babu, A P Rani, U P Naidu, M U Srinivas, N R Rajagopalan, R J-Clin-Pharmacol. 2002 June; 42(6): 670-5 0091-2700
•
Peroxisome proliferator-activated receptor-gamma agonist, rosiglitazone, protects against nephropathy and pancreatic islet abnormalities in Zucker fatty rats. Author(s): SmithKline Beecham Pharmaceuticals, Harlow, Essex, UK. Source: Buckingham, R E Al Barazanji, K A Toseland, C D Slaughter, M Connor, S C West, A Bond, B Turner, N C Clapham, J C Diabetes. 1998 Aug; 47(8): 1326-34 0012-1797
•
PPARalpha activation by Wy 14643 induces transactivation of the rat UCP-1 promoter without increasing UCP-1 mRNA levels and attenuates PPARgamma-mediated increases in UCP-1 mRNA levels induced by rosiglitazone in fetal rat brown adipocytes. Author(s): Department of Vascular Biology, SmithKline Beecham Pharmaceuticals, Harlow, CM19 5AW, United Kingdom. Source: Teruel, T Clapham, J C Smith, S A Biochem-Biophys-Res-Commun. 1999 October 22; 264(2): 311-5 0006-291X
•
Rosiglitazone (BRL 49653) enhances insulin secretory response via phosphatidylinositol 3-kinase pathway. Author(s): Department of Veterinary Medicine, National Chung Hsing University, Taichung, Taiwan. Source: Yang, C Chang, T J Chang, J C Liu, M W Tai, T Y Hsu, W H Chuang, L M Diabetes. 2001 November; 50(11): 2598-602 0012-1797
•
Rosiglitazone and retinoic acid induce uncoupling protein-1 (UCP-1) in a p38 mitogen-activated protein kinase-dependent manner in fetal primary brown adipocytes. Author(s): Departamento de Bioquimica y Biologia Molecular II, Facultad de Farmacia, Universidad Complutense, 28040 Madrid, Spain. Source: Teruel, T Hernandez, R Benito, M Lorenzo, M J-Biol-Chem. 2003 January 3; 278(1): 263-9 0021-9258
•
Rosiglitazone but not metformin enhances insulin- and exercise-stimulated skeletal muscle glucose uptake in patients with newly diagnosed type 2 diabetes. Author(s): Turku PET Centre, University of Turku, FIN-20521 Turku, Finland. Source: Hallsten, K Virtanen, K A Lonnqvist, F Sipila, H Oksanen, A Viljanen, T Ronnemaa, T Viikari, J Knuuti, J Nuutila, P Diabetes. 2002 December; 51(12): 3479-85 0012-1797
•
Rosiglitazone fails to improve hypertriglyceridemia and glucose tolerance in CD36deficient BN.SHR4 congenic rat strain. Author(s): Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic.
[email protected]
54
Rosiglitazone
Source: Seda, O Kazdova, L Krenova, D Kren, V Physiol-Genomics. 2003 January 15; 12(2): 73-8 1531-2267 •
Rosiglitazone in the treatment of type 2 diabetes mellitus: a critical review. Author(s): Department of Pharmacy Practice, Nesbitt School of Pharmacy, Wilkes University, Wilkes-Barre, Pennsylvania 18766, USA.
[email protected] Source: Malinowski, J M Bolesta, S Clin-Ther. 2000 October; 22(10): 1151-68; discussion 1149-50 0149-2918
•
Rosiglitazone prevents the onset of hyperglycaemia and proteinuria in the Zucker diabetic fatty rat. Author(s): SmithKline Beecham Pharmaceuticals, Harlow, Essex, UK. Source: Smith, S A Lister, C A Toseland, C D Buckingham, R E Diabetes-Obes-Metab. 2000 December; 2(6): 363-72 1462-8902
•
Rosiglitazone. Author(s): Division of Endocrinology, Diabetes and Metabolic Diseases, Jefferson Medical College, Philadelphia, PA 19107, USA. Source: Goldstein, B J Int-J-Clin-Pract. 2000 June; 54(5): 333-7 1368-5031
•
Rosiglitazone: a review of its use in the management of type 2 diabetes mellitus. Author(s): Adis International Limited, Miarangi Bay, Auckland, New Zealand.
[email protected] Source: Wagstaff, A J Goa, K L Drugs. 2002; 62(12): 1805-37 0012-6667
•
Systemic exposure to rosiglitazone is unaltered by food. Author(s): SmithKline Beecham Clinical Pharmacology Unit, Presbyterian Medical Center of the University of Pennsylvania Health System, Philadelphia 19104, USA.
[email protected] Source: Freed, M I Allen, A Jorkasky, D K DiCicco, R A Eur-J-Clin-Pharmacol. 1999 March; 55(1): 53-6 0031-6970
•
The effect of acarbose on the pharmacokinetics of rosiglitazone. Author(s): SmithKline Beecham Pharmaceuticals, 709 Swedeland Road, King of Prussia, PA 19041, USA.
[email protected] Source: Miller, A K Inglis, A M Culkin, K T Jorkasky, D K Freed, M I Eur-J-ClinPharmacol. 2001 May; 57(2): 105-9 0031-6970
•
The thiazolidinedione rosiglitazone (BRL-49653) lowers blood pressure and protects against impairment of endothelial function in Zucker fatty rats. Author(s): Department of Medicine, University of Liverpool, UK. Source: Walker, A B Chattington, P D Buckingham, R E Williams, G Diabetes. 1999 July; 48(7): 1448-53 0012-1797
•
Therapeutic index for rosiglitazone in dietary obese rats: separation of efficacy and haemodilution. Author(s): Department of Medicine, University of Liverpool, Liverpool. Source: Pickavance, L C Tadayyon, M Widdowson, P S Buckingham, R E Wilding, J P Br-J-Pharmacol. 1999 December; 128(7): 1570-6 0007-1188
•
Troglitazone, but not rosiglitazone, inhibits Na/H exchange activity and proliferation of macrovascular endothelial cells. Author(s): Cell Biology of Diabetes Laboratory, Baker Medical Research Institute, P.O. Box 6492, Victoria, Melbourne 8008, Australia. Source: de Dios, S T Hannan, K M Dilley, R J Hill, M A Little, P J J-DiabetesComplications. 2001 May-June; 15(3): 120-7 1056-8727
Nutrition 55
•
Using thiazolidinediones: rosiglitazone and pioglitazone in clinical practice. Source: Peters, A L Am-J-Manag-Care. 2001 April; 7(3 Suppl): S87-95; quiz S96-7 10961860
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
•
The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov
•
The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov
•
The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/
•
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/
•
Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/
•
Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/
•
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
•
Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html
•
Google: http://directory.google.com/Top/Health/Nutrition/
•
Healthnotes: http://www.healthnotes.com/
•
Open Directory Project: http://dmoz.org/Health/Nutrition/
•
Yahoo.com: http://dir.yahoo.com/Health/Nutrition/
•
WebMDHealth: http://my.webmd.com/nutrition
•
WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
57
CHAPTER 3. CLINICAL TRIALS AND ROSIGLITAZONE Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning rosiglitazone.
Recent Trials on Rosiglitazone The following is a list of recent trials dedicated to rosiglitazone.8 Further information on a trial is available at the Web site indicated. •
A Randomized Trial of Rosiglitazone for Ulcerative Colitis Condition(s): Ulcerative Colitis; Inflammatory Bowel Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); GlaxoSmithKline Purpose - Excerpt: This is a multicenter, randomized, double-blind, placebo-controlled study evaluating rosiglitazone: 4 mg tablets or placebo tablets administered orally twice daily for 12 weeks. The purpose of the study is to evaluate the efficacy and safety of rosiglitazone in the treatment of mild to moderately active ulcerative colitis. Disease activity will be measured using a standard disease activity index. Calculation of the index requires patients to undergo flexible sigmoidoscopy at the start of the study and at week 12. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00065065
8
These are listed at www.ClinicalTrials.gov.
58
Rosiglitazone
•
Metformin and Rosiglitazone, Alone or in Combination, in HIV-Infected Patients with Insulin and Fat Abnormalities Condition(s): HIV Infections; Lipodystrophy; Hyperinsulinemia Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: The purpose of this study is to see whether metformin alone, rosiglitazone alone, or metformin and rosiglitazone together will lower insulin levels in the blood and decrease fat in the abdomen or other parts of the body. Studies have shown that certain anti-HIV medications can cause a number of side effects, including high blood sugar (resulting from the body's failure to use insulin), high insulin, and excess fat build-up in the abdominal area. These side effects are known to increase the risk of heart disease. Metformin and rosiglitazone are 2 drugs that have been shown to lower insulin resistance and lessen abdominal fat in patients who are not HIV-infected. This study will investigate the use of these drugs in HIV-infected patients. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00015691
•
Rosiglitazone to Treat Patients with Heart Failure and Glucose Intolerance or Type II Diabetes Condition(s): Congestive Heart Failure Study Status: This study is currently recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: This study will evaluate the safety and effectiveness of the drug rosiglitazone for improving heart function in patients with heart failure and glucose intolerance or type II (adult-onset) diabetes, or both. Because of a lowered sensitivity to the hormone insulin, patients with type II diabetes or glucose-intolerance do not regulate glucose (sugar) effectively. Rosiglitazone is used to treat type II diabetes, but it is not commonly given to patients with heart failure because it can cause leg swelling and, rarely, pulmonary edema. However, patients with heart failure who also have glucose intolerance or type II diabetes generally fare worse than those with heart failure alone, and therapies that decrease insulin resistance may be beneficial to these patients. Patients 21 years of age and older with heart failure and type II diabetes or glucose intolerance, or both, may be eligible for this study. Patients must be stable on current therapy for heart failure and must not have any planned surgeries for coronary artery disease. Candidates will be admitted to the NIH Clinical Center for from 2 to 7 days for screening procedures, which include a medical history and physical examination, blood and urine tests, electrocardiogram (ECG), chest x-ray, magnetic resonance imaging (MRI), exercise testing, and echocardiography (ultrasound test of the heart). Participants will be randomly assigned to receive either rosiglitazone or placebo (an identicallooking pill with no active ingredient). They will take one tablet a day for the first month, one tablet twice a day for the second month, and then two tablets twice a day from the third month to the end of the study at 6 months. During the treatment period, patients will have a history, physical examination, and blood tests every 4 weeks, exercise testing and echocardiography at 3 and 6 months, and urinalysis, electrocardiogram and MRI at 6 months. To check for fluid accumulation in the legs or lungs, patients will report their weight and symptoms every 2 weeks throughout the study. After the 6-month treatment period, patients will be put back on the diabetes
Clinical Trials 59
medicines they were taking before the study. Their physicians will be notified of possible modifications in treatment for maintaining optimum glucose tolerance. Six months after completing treatment (one year after beginning the study), patients will return to the Clinical Center for blood tests to measure the long-term effects of rosiglitazone and to evaluate progress. They will then be invited to return to the clinic for annual checkups, if possible, or for yearly follow-up by mail or telephone to review their health status. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00064727 •
Rosiglitazone in Treating Patients With Liposarcoma Condition(s): adult liposarcoma; recurrent adult soft tissue sarcoma Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); Dana-Farber/Harvard Cancer Center Purpose - Excerpt: RATIONALE: Rosiglitazone may help liposarcoma cells develop into normal fat cells. PURPOSE: Phase II trial to study the effectiveness of rosiglitazone in treating patients who have liposarcoma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004180
•
Effects of Rosiglitazone on Blood Vessels in Patients with High Blood Pressure and High Cholesterol Condition(s): Hypercholestrolemia; Hypertension Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: Cells in the lining of blood vessels produce various substances that cause the vessels to dilate (relax) and constrict (tighten), thereby regulating blood flow. In patients with high blood pressure and high cholesterol, the blood vessels do not dilate properly. This study will investigate the effects of rosiglitazone-a drug used to improve the action of insulin in diabetic patients-on blood flow by examining its effects on endothelin (a substance that causes vessel constriction), and other substances produced by the vessel-lining cells. Adults with blood pressure recordings of 140/90 mmHg or higher on at least three separate days or with a blood cholesterol level of at least 240 mg/dl may be eligible for this study. Candidates will be screened with a medical history and physical examination, blood pressure recordings, blood and urine tests. This "crossover" study involves two separate treatment periods; that is, participants will take either rosiglitazone or placebo (an inactive look-alike pill) once a day for 8 weeks, then no drug for 4 weeks, and then the alternative treatment for the next 8 weeks. Patients will continue to take their high blood pressure medicines during the first 6 weeks of each treatment period. They will stop the medication 2 weeks before the following procedures, which are done at the end of each 8-week treatment period:
60
Rosiglitazone
Strain gauge plethysmography-A small catheter is placed through a needle into an artery at the bend of the arm for measuring blood pressure and drawing blood samples during the study. Pressure cuffs are placed on the wrist and upper arm, and a strain gauge (a rubber band device) is placed around the forearm to measure forearm blood flow. When the cuffs are inflated, blood flows into the arm, stretching the strain gauge at a rate proportional to the flow, and the measurement is recorded. Small doses of four drugs-acetylcholine, bradykinin, sodium nitroprusside and BQ-123-are given through the catheter. Acetylcholine slows the heart rate. Bradykinin stimulates the release of a substance that causes blood vessels to dilate and can lower blood pressure. Sodium nitroprusside causes blood vessels to dilate and is used to treat high blood pressure and heart failure. BQ-123 blocks the blood vessel-constricting activity of endothelin. Brachial ultrasound reactivity study-A baseline ultrasound image (picture produced using sound waves) of the brachial artery (artery located at the bend of the arm) is taken and blood flow measurements are recorded. Then, a pressure cuff is placed around the upper forearm, inflated for 5 minutes to stop blood flow to the forearm, and then released. Images of the artery and flow measurements are repeated. After a 15-minute rest, new baseline images are taken and flow measurements obtained. A small amount of nitroglycerin is then sprayed under the tongue and after 3 minutes, blood flow measurements and brachial artery images are recorded once more. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006071 •
Rosiglitazone and exercise training: effects on HIV-infected people with insulin resistance, hypertriglyceridemia, and adipose tissue maldistribution Condition(s): HIV Infections; Insulin Resistance Study Status: This study is completed. Sponsor(s): National Center for Research Resources (NCRR); The Campbell Foundation Purpose - Excerpt: Several complications have become prevalent in people living with HIV/AIDS, including increased blood sugar, increased blood fats and cholesterol, and fat tissue redistribution. The causes of these complications are not well understood and effective treatments have not been identified. We propose to test the efficacy and safety of 2 treatments for these complications in people living with HIV/AIDS: aerobic, weight lifting exercise training, and a new insulin-sensitizing agent called rosiglitazone (Avandia). Exercise and rosiglitazone have been effective and moderately safe when used in HIV-seronegative people with diabetes, but a specific trial is needed to test efficacy and safety in people living with HIV/AIDS. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00025753
•
Rosiglitazone in the Treatment of HIV-Associated Hyperlipidemia Condition(s): HIV Infections; Hyperlipidemia Study Status: This study is completed. Sponsor(s): National Center for Research Resources (NCRR)
Clinical Trials 61
Purpose - Excerpt: The purpose of this research is to study the effects of rosiglitazone, a drug usually taken for Type II diabetes, on HIV-associated hyperlipidemia. HIVassociated lipodystrophy is a medical condition characterized by gradual changes in the distribution of body fat. The body fat located in the extremities and face disappears while body fat around the abdomen and upper back increases. Certain biochemical changes occur in association with these changes in fat distribution. Lipid levels particularly serum triglycerides are increased. HDL, the "good cholesterol" is decreased. Higher than normal level of insulin or insulin resistance is also found in this condition. This latter condition is one of the hallmarks of Type II diabetes. The protease inhibitors, a class of HIV medications, are associated with the occurrence of HIV-associated lipodystrophy. It has been suggested that a biochemical pathway known as the peripheral peroxisomal activating receptor (PPAR) gamma system is blocked leading to the onset of this condition. Rosiglitazone is a new drug approved by the FDA in 1999 for the treatment of type II diabetes. It lowers blood sugar by improving insulin resistance, which as mentioned before, is the hallmark of Type II diabetes. It has also been noted to improve blood lipid levels. Rosiglitazone works by stimulating the PPAR gamma system. It is hoped that this drug can turn on the PPAR system and reverse the HIV-associated lipodystrophy syndrome. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006493
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 “rosiglitazone” (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/
•
For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html
•
For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/
•
For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm
62
Rosiglitazone
•
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
•
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
•
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
•
For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm
•
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/
•
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
•
For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm
•
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
•
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
•
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
•
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
63
CHAPTER 4. PATENTS ON ROSIGLITAZONE 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 “rosiglitazone” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on rosiglitazone, we have not necessarily excluded nonmedical patents in this bibliography.
Patents on Rosiglitazone By performing a patent search focusing on rosiglitazone, 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 will tell you how to obtain this information later in the chapter. The following is an 9Adapted
from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
64
Rosiglitazone
example of the type of information that you can expect to obtain from a patent search on rosiglitazone: •
Non-aqueous aerosol formulation comprising rosiglitazone maleate, a non-aqueous carrier, and an amino acid stabilizer Inventor(s): Adjei; Akwete L. (Bridgewater, NJ), Cutie; Anthony J. (Bridgewater, NJ), Sexton; Frederick A. (Fair Haven, NJ) Assignee(s): Aeropharm Technology, Inc. () Patent Number: 6,468,507 Date filed: October 31, 2000 Abstract: A non-aqueous medicinal aerosol formulation comprising rosiglitazone maleate, a fluid carrier, and an amino acid stabilizer. The aerosol formulation may also include drug combination formulations comprising rosiglitazone maleate and a second anti-diabetic medicament. Excerpt(s): This invention relates to a medicinal aerosol formulation, and more particularly, to a medicinal aerosol formulation comprising rosiglitazone maleate and a protective colloid stabilizer. Delivery of drugs to the lung by way of inhalation is an important means of treating a variety of conditions, including such common local conditions as cystic fibrosis, pneumonia, bronchial asthma and chronic obstructive pulmonary disease and some systemic conditions including pain management, immune deficiency, hormonal therapy, erythropoiesis, diabetes, etc. Anti-diabetic drugs, e.g. an insulin, are among the drugs that are administered to the lung for such purposes. Such drugs are commonly administered to the lung in the form of an aerosol of particles of respirable size (less than about 10.mu.m in diameter). In order to assure proper particle size in the aerosol, particles can be prepared in respirable size and then incorporated into a colloidal dispersion containing either a propellant, as a pressurized metered dose inhaler (MDI), or air such as is the case with a dry powder inhaler (DPI). Alternatively, formulations can be prepared in solution or emulsion form in order to avoid the concern for proper particle size in the formulation. Solution formulations must nevertheless be dispensed in a manner that produces particles or droplets of respirable size. For MDI preparations, once prepared, the aerosol formulation is filled into an aerosol canister equipped with a metered dose valve. In the hands of the patient the formulation is dispensed via an actuator adapted to direct the dose from the valve to the patient. Web site: http://www.delphion.com/details?pn=US06468507__
•
Process for the preparation of rosiglitazone maleate Inventor(s): Vyas; Sharad Kumar (Ahmedabad, IN) Assignee(s): Torrent Pharmaceuticals, Ltd. (abmedabad, In) Patent Number: 6,515,132 Date filed: September 14, 2001 Abstract: The invention discloses a process for the preparation of a pyridine derivative namely 5-{4-2(N-methyl-N(2-pyridyl)amino ethoxy]benzyl]thiazolidine-2,4-dione maleate comprising the steps of:(a) reacting 2-chloropyridine with 2-(N-methyl amino)ethanol;(b) coupling 2-(N-methyl-N-(2-pyridyl) amino)ethanol) obtained in step (a) and 4-fluorobenzaldehyde in an aprotic polar solvent with an alkali metal hydroxide
Patents
65
or an alkali metal alkoxide as base.(c) isolating the product of the coupling reaction viz 4-[2-(N-methyl-N-(2-pyridyl) amino) ethoxy]benzaldehyde;(d) converting said isolated benzaldehyde compound of step (c) into 5-[4-[2-N-methyl-N-(2-pyridyl) amino)ethoxy]benzyl]thiazolidine-2,4-dione in a known manner and(e) converting said thiazolidine-2,4-dione compound obtained in step (d) into a pharmaceutically acceptable maleate salt. Excerpt(s): The present invention relates to a process for the preparation of 5-[4-[2-(Nmethyl-N-(2-pyridyl) amino) ethoxy]benzyl]thiazolidine-2,4-dione maleate, namely, rosiglitazone maleate, the antidiabetic compound, which is the preferred drug for noninsulin dependent diabetes mellitus (NIDDM). Diabetes mellitus is a complex, chronically, progressive disease, which can eventually adversely affect the functioning of the kidneys, eyes, nervous and vascular systems. Most individuals diagnosed with diabetes mellitus show symptoms for non insulin dependent diabetes mellitus (NIDDM) that is, Type II diabetes. Type II diabetes is a debilitating disease that arises from improper energy storage and utilization. Type II diabetes is defined by high plasma glucose levels and is characterized by both peripheral insulin resistance and insufficient insulin secretion by the.beta.-cells of the pancreas. The current approach for handling hyperglycemia is to alleviate insulin resistance rather than to stimulate insulin secretion. The thiazolidinedione class of antidiabetics such as pioglitazone, englitazone, troglitazone and ciglitazone have been shown to alleviate insulin resistance in humans. Since, rosiglitazone is the preferred drug for non-insulin dependent diabetes mellitus, hence, the process for its production, yield obtained and costs involved are all constantly being critically surveyed for optimization. Web site: http://www.delphion.com/details?pn=US06515132__
Patent Applications on Rosiglitazone 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 rosiglitazone: •
Combination of a PTPase inhibitor and a thiazolidinedione agent Inventor(s): Jordan, Ronald Arlie; (Richboro, PA), Robert Vitou, Philippe John; (Paris, FR) Correspondence: Arnold S. Milowsky; 5 Giralda Farms; Madison; NJ; 07940; US Patent Application Number: 20020198203 Date filed: June 6, 2002 Abstract: This invention provides methods of using a pharmacological combination of one or more PTPase inhibiting agents and one or more thiazolidinedione agents, including pioglitizone or rosiglitazone, for treatment in a mammal of Syndrome X or type II diabetes or metabolic disorders mediated by insulin resistance or hyperglycemia. Further included in this invention is a method of modulating blood glucose levels in a mammal utilizing the combination of one or more PTPase inhibiting agents and one or more thiazolidinedione agents.
10
This has been a common practice outside the United States prior to December 2000.
66
Rosiglitazone
Excerpt(s): This application claims priority from copending provisional application Serial No. 60/296,501, filed Jun. 7, 2001, the entire disclosure of which is hereby incorporated by reference. This invention relates to pharmaceutical combinations of a PTPase inhibiting compound and a thiazolidinedione agent. Particularly, this invention concerns methods of treating or inhibiting Syndrome X or type II diabetes and related conditions in a mammal utilizing combinations of these two classes of pharmacological agents. The prevalence of insulin resistance in glucose intolerant subjects has long been recognized. Reaven et al (American Journal of Medicine 1976, 60, 80) used a continuous infusion of glucose and insulin (insulin/glucose clamp technique) and oral glucose tolerance tests to demonstrate that insulin resistance existed in a diverse group of nonobese, nonketotic subjects. These subjects ranged from borderline glucose tolerant to overt, fasting hyperglycemia. The diabetic groups in these studies included both insulin dependent (IDDM) and noninsulin dependent (NIDDM) subjects. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Cyclopropyl-fused pyrrolidine-based inhibitors of dipeptidyl peptidase IV and method Inventor(s): Augeri, David J.; (Princeton, NJ), Betebenner, David A.; (Lawrenceville, NJ), Hamann, Lawrence G.; (Cherry Hill, NJ), Magnin, David R.; (Hamilton, NJ), Robl, Jeffrey A.; (Newtown, PA), Sulsky, Richard B.; (West Trenton, NJ) Correspondence: Marla J Mathias; Bristol-myers Squibb Company; Patent Department; P O Box 4000; Princeton; NJ; 08543-4000; US Patent Application Number: 20020019411 Date filed: February 16, 2001 Abstract: Dipeptidyl peptidase IV (DP 4) inhibiting compounds are provided having the formula 1where x is 0 or 1 and y is 0 or 1 (provided that x=1 when y=0 and x=0 when y=1);n is 0 or 1; X is H or CN;and wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are as described herein.A method is also provided for treating diabetes and related diseases, especially Type II diabetes, and other diseases as set out herein, employing such DP 4 inhibitor or a combination of such DP 4 inhibitor and one or more of another antidiabetic agent such as metformin, glyburide, troglitazone, pioglitazone, rosiglitazone and/or insulin and/or one or more of a hypolipidemic agent and/or antiobesity agent and/or other therapeutic agent. Excerpt(s): This application takes priority from U.S. provisional application No. 60/188,555, filed Mar. 10, 2000. The present invention relates to cyclopropyl-fused pyrrolidine-based inhibitors of dipeptidyl peptidase IV (DP-4), and to a method for treating diabetes, especially Type II diabetes, as well as hyperglycemia, Syndrome X, diabetic complications, hyperinsulinemia, obesity, atherosclerosis and related diseases, as well as various immunomodulatory diseases and chronic inflammatory bowel disease, employing such cyclopropyl-fused pyrrolidines alone or in combination with another type antidiabetic agent and/or other type therapeutic agent. Depeptidyl peptidase IV (DP-4) is a membrane bound non-classical serine aminodipeptidase which is located in a variety of tissues (intestine, liver, lung, kidney) as well as on circulating Tlymphocytes (where the enzyme is known as CD-26). It is responsible for the metabolic cleavage of certain endogenous peptides (GLP-1(7-36), glucagon) in vivo and has demonstrated proteolytic activity against a variety of other peptides (GHRH, NPY, GLP2, VIP) in vitro.
Patents
67
Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Medicinal aerosol formulation Inventor(s): Adjei, Akwete L.; (Bridgewater, NJ), Cutie, Anthony J.; (Bridgewater, NJ), Sexton, Frederick A.; (Fair Haven, NJ) Correspondence: Frommer Lawrence & Haug L.L.P.; 745 Fifth Avenue; New York; NY; 10151; US Patent Application Number: 20030012739 Date filed: July 9, 2002 Abstract: This invention relates to medicinal aerosol and more formulation and more particularly, to a medicinal aerosol formulation containing rosiglitazone maleate and a fluid carrier. Excerpt(s): This application is a continuation application of application Ser. No. 09/703,068, filed on Oct. 31, 2000 which claims priority from U.S. provisional application Serial No. 60/201,058 filed May 1, 2000, which is incorporated herein by reference. This invention relates to a medicinal aerosol formulation, and more particularly, to a medicinal aerosol formulation comprising a rosiglitazone maleate. Delivery of drugs to the lung by way of inhalation is an important means of treating a variety of conditions, including such common local conditions as cystic fibrosis, pneumonia, bronchial asthma and chronic obstructive pulmonary disease and some systemic conditions, including hormone replacement, pain management, immune deficiency, erythropoiesis, diabetes, etc. Anti-diabetic drugs, e.g. an insulin, are among the drugs that are administered to the lung for such purposes. Such drugs are commonly administered to the lung in the form of an aerosol of particles of respirable size (less than about 10.mu.m in diameter). The aerosol formulation can be presented as a liquid or a dry powder. In order to assure proper particle size in a liquid aerosol, particles can be prepared in respirable size and then incorporated into a colloidial dispersion either containing a propellant as a metered dose inhaler (MDI) or air, such as in the case of a dry powder inhaler (DPI). Alternatively, formulations can be prepared in solution form in order to avoid the concern for proper particle size in the formulation. Solution formulations must nevertheless be dispensed in a manner that produces particles or droplets of respirable size. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
•
Novel remedies with the use of beta 3 agonist Inventor(s): Ogawa, Kohei; (Shizuoka, JP), Umeno, Hiroshi; (Shizuoka, JP) Correspondence: Young & Thompson; 745 South 23rd Street 2nd Floor; Arlington; VA; 22202 Patent Application Number: 20030018061 Date filed: July 29, 2002 Abstract: Provided is a therapeutic agent comprising at least one member selected from the group consisting of an anticholinergic agent, a monoamine reuptake inhibitor, a lipase inhibitor, a selective serotonin reuptake inhibitor, insulin, an insulin secretagogue, biguanide, an.alpha.-glucosidase inhibitor, an insulin resistance improving agent, a
68
Rosiglitazone
HMG-CoA reductase inhibitor, an anion exchange resin, a clofibrate type drug and a nicotinic acid type drug, and a compound having a.beta.3 agonist activity. The.beta.3agonist has an activity of inhibiting dysuria. Further, when used together with a remedy for dysuria such as propiverine, oxybutynin hydrochloride or tolterodine, it exerts an enhanced anti-dysuria effect. When used together with an antiobestic agent such as sibutramine or orlistat, it exerts an enhanced antiobestic effect. When used together with an antidiabetic agent such as insulin, glibenclamide, acarbose or rosiglitazone, it exerts an enhanced antidiabetic effect. When used together with an antilipemic agent such as bezafibrate or pravastatin, it exerts an enhanced antilipemic effect. Excerpt(s): The present invention relates to novel therapeutic agents that use a.beta.3 agonist.beta. adrenaline receptors are classified into.beta.1,.beta.2, and.beta.3. It is considered that.beta.1 stimulation increases the pulse rate,.beta.2 stimulation induces relaxation of smooth muscle tissue and reduces the blood pressure, and.beta.3 promotes lipolysis of adipose cells and increases thermogenesis. Accordingly, it is shown that a.beta.3 agonist is useful as a therapeutic agent for diabetes, obesity and prevention of hyperlipidemia (Nature 309, p163-165 (1984); Int. J. Obes. Relat. Metab. Disord. 20, p191199 (1996); Drug Development Research 32, p69-76 (1994); J. Clin. Invest. 101, p2387-2393 (1998)). Recently, it has been shown that.beta. adrenaline receptors are expressed in the detrusor muscle, and that the detrusor muscle relaxes with a.beta.3-agonist (J. Urinol. 161, p680-685 (1999); J. Pharmacol. Exp. Ther. 288, p1367-1373 (1999)). On the other hand, while flavoxate hydrochloride, oxybutynin hydrochloride, propiverine hydrochloride and tolterodine have been used in treatment of patients affected by pollakiuria or incontinence of urine up to now (Folia Pharmacologica Japonica, Vol. 113, p157-166 (1999); Eur. J. Pharmaco. 349, p285-292 (1998)), their side effects include mouth dryness, difficulty in urinating, and constipation (RINSHOU HINYOUKIKA, Vol. 52, p277-285 (1998)), and the situation can not be considered satisfactory. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Pharmaceuticals for treating obesity Inventor(s): Berger, Joel P.; (Hoboken, NJ), Doebber, Thomas W.; (Scotch Plains, NJ), Leibowitz, Mark D.; (San Diego, CA), Moller, David E.; (Bedminster, NJ), Mosley, Ralph T.; (Roselle, NJ), Tolman, Richard L.; (Menlo Park, CA), Ventre, John; (Nutley, NJ), Zhang, Bei B.; (Edison, NJ), Zhou, Gaochao; (Scotch Plains, NJ) Correspondence: Merck & CO., INC.; Patent Department; P.O. Box 2000 - Ry60-30; Rahway; NJ; 07065-0907; US Patent Application Number: 20030032581 Date filed: September 11, 2002 Abstract: Compounds which are antagonists of strong PPAR-gamma agonists, such as rosiglitazone, and are also partial agonists of the PPAR-gamma receptor, are active agents for correcting or reducing obesity. For example, 1-(p-chlorobenzyl)-5-chloro-3thiophenylindole-2-carboxylic acid, is characterized as being a potent and selective ligand for PPAR-gamma which has partial agonist (<30% maximal effects relative to rosiglitazone) and antagonist activity in cell-free and cell-based assays for the PPARgamma receptor. The compound is a potent agent for reducing obesity and insulin resistance in fat-fed C57BL/6J mice. This compound and other PPAR-gamma antagonists/partial agonists and pharmaceutically acceptable salts are effective in the treatment of obesity and/or diabetes and/or insulin resistance.
Patents
69
Excerpt(s): This invention relates to obesity and methods of treating or preventing obesity. In addition, the invention relates to methods for treatment or prevention of insulin resistance, Type II diabetes, and lipid disorders. Excessive weight, and in extreme cases obesity, is a widespread medical problem in the United States and elsewhere as the new millenium approaches. This may be due in part to sedentary life styles and poor diet (high in fats and carbohydrates), as well as to a genetic predisposition in many cases. Pharmaceuticals have been marketed in the past to help control excessive weight and obesity. These have typically tried to achieve weight loss by reducing the appetite. Drugs used to reduce appetite have not been universally successful. Many are stimulants and have been abused, and others have had unexpected, and sometimes serious side effects (e.g., fen-phen). An approach that has so far not been exploited successfully is the development of pharmaceuticals that control excessive weight and obesity using a metabolic approach by modulation of receptors that can influence weight gain. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Treatment of diabetes with rosiglitazone and insulin Inventor(s): Smith, Stephen Alistair; (Bramfield, GB) Correspondence: Glaxosmithkline; Corporate Intellectual Property - Uw2220; P.O. Box 1539; King OF Prussia; PA; 19406-0939; US Patent Application Number: 20020028768 Date filed: August 13, 2001 Abstract: A method for the treatment of diabetes mellitus and conditions associated with diabetes mellitus in a mammal, which method comprises administering an effective non-toxic and pharmaceutically acceptable amount of Compound (I) and insulin to a mammal in need thereof. Excerpt(s): This invention relates to a method of treatment, in particular to a method for the treatment of diabetes mellitus, especially non-insulin dependent diabetes (NIDDM) or Type II diabetes and conditions associated with diabetes mellitus. Insulin is a front line treatment agent for Type I diabetes (or Insulin Dependent Diabetes). It is also used as an antihyperglycaemic agent in the treatment of NIDDM. European Patent Application, Publication Number 0,306,228 relates to certain thiazolidinedione derivatives disclosed as having antihyperglycaemic and hypolipidaemic activity. One particular thiazolidinedione disclosed in EP 0306228 is 5-[4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]benzyl]thiazolidine-2,4-dione (hereinafter `Compound (I)`). WO94/05659 discloses certain salts of Compound (I) including the maleate salt at example 1 thereof. 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 rosiglitazone, 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:
70
Rosiglitazone
Under “Issued Patents,” click “Quick Search.” Then, type “rosiglitazone” (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 rosiglitazone. You can also use this procedure to view pending patent applications concerning rosiglitazone. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.
71
CHAPTER 5. BOOKS ON ROSIGLITAZONE Overview This chapter provides bibliographic book references relating to rosiglitazone. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on rosiglitazone include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.
Chapters on Rosiglitazone In order to find chapters that specifically relate to rosiglitazone, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and rosiglitazone 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 “rosiglitazone” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on rosiglitazone: •
Oral Agents Source: in Edelman, S.V. and Henry, R.R. Diagnosis and Management of Type 2 Diabetes. Caddo, OK: Professional Communications, Inc. 2002. p. 69-120. Contact: Available from Professional Communications, Inc., Fulfillment Center, PO Box 10, Caddo, OK 74729-0010. (800)337-9838. Fax (580)367-9989. E-mail:
[email protected]. ISBN: 1884735754. PRICE: $21.95, plus shipping and handling. Summary: This chapter on the use of oral hypoglycemic agents is from a handbook for primary care providers that offers a concise overview of the diagnosis and management of type 2 diabetes. The majority of patients with type 2 diabetes have less than ideal metabolic control despite the medical community's understanding of the underlying pathophysiologic mechanisms of hyperglycemia (high blood glucose) and the availability of a wide variety of new treatment options. The authors contend that failure to achieve glycemic (blood glucose) goals is related in part to a misconception by
72
Rosiglitazone
patients and caregivers that type 2 diabetes is a mild disease, and not as serious as type 1 diabetes. Drug therapy with oral antidiabetes agents is required when dietary modification and exercise therapy do not result in normalization or near normalization of metabolic abnormalities. Topics include the pathophysiologic basis of pharmacologic therapy, the importance of controlling postprandial (after a meal) hyperglycemia, intensive therapy in type 2 diabetes, diabetes prevention study results, oral antidiabetes agents, thiazolidinediones (including rosiglitazone, pioglitazone), metformin (Glucophage), alpha-glucosidase inhibitors, sulfonylureas, meglitinides, monotherapy with oral antidiabetes agents, combination therapy with oral antidiabetes agents, taking patients with type 2 diabetes off insulin, and drugs under development. 5 figures. 4 tables. 31 references.
73
CHAPTER 6. PERIODICALS AND NEWS ON ROSIGLITAZONE Overview In this chapter, we suggest a number of news sources and present various periodicals that cover rosiglitazone.
News Services and Press Releases One of the simplest ways of tracking press releases on rosiglitazone 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 “rosiglitazone” (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 rosiglitazone. 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 “rosiglitazone” (or synonyms). The following was recently listed in this archive for rosiglitazone: •
Glaxo's Avandia not recommended as monotherapy in Scotland Source: Reuters Industry Breifing Date: March 09, 2004
•
Rosiglitazone reduces inflammatory response and tissue damage in arthritis model Source: Reuters Industry Breifing Date: January 22, 2004
74
Rosiglitazone
•
Dr. Reddy's files with US FDA for generic Avandia Source: Reuters Industry Breifing Date: September 09, 2003
•
Rosiglitazone reduces hyperinsulinemia in type 2 diabetics Source: Reuters Industry Breifing Date: August 20, 2003
•
More signs rosiglitazone effective for HIV lipodystrophy Source: Reuters Medical News Date: July 14, 2003
•
Rosiglitazone reduces restenosis after stenting in type 2 diabetics Source: Reuters Industry Breifing Date: June 16, 2003
•
Type 2 diabetes control improves when nateglinide is added to rosiglitazone Source: Reuters Industry Breifing Date: June 11, 2003
•
Short-term rosiglitazone enhances ovulation in polycystic ovary syndrome Source: Reuters Industry Breifing Date: April 08, 2003
•
Rosiglitazone may be cardioprotective in type 2 diabetics with CAD Source: Reuters Industry Breifing Date: March 04, 2003
•
FDA approves use of rosiglitazone with insulin Source: Reuters Medical News Date: February 28, 2003
•
FDA approves use of GlaxoSmithKline's Avandia with insulin Source: Reuters Industry Breifing Date: February 28, 2003
•
Rosiglitazone improves insulin sensitivity, lowers blood pressure in hypertensives Source: Reuters Industry Breifing Date: January 30, 2003
•
Rosiglitazone enhances glucose uptake in type 2 diabetics Source: Reuters Industry Breifing Date: January 22, 2003
•
Rosiglitazone restores renal dopamine receptor function in hyperinsulinemic rats Source: Reuters Industry Breifing Date: December 31, 2002
•
Rosiglitazone improves insulin sensitivity, body fat distribution in HIV+ patients Source: Reuters Medical News Date: November 11, 2002
•
Glaxo ends deal with Bristol-Myers on Avandia diabetes drug Source: Reuters Industry Breifing Date: August 08, 2002
•
Diabetes drug rosiglitazone results in minimal hepatotoxicity Source: Reuters Industry Breifing Date: April 29, 2002
Periodicals and News 75
•
Glaxo's Avandia and Takeda's Actos get strengthened cardiovascular warnings Source: Reuters Industry Breifing Date: April 26, 2002
•
Diabetes drug Avandia poses minimal harm to liver Source: Reuters Health eLine Date: April 26, 2002
•
Glaxo reprimanded over Avandia ad Source: Reuters Industry Breifing Date: December 14, 2001
•
Rosiglitazone drives fat from muscle cells Source: Reuters Medical News Date: September 12, 2001
•
Addition of rosiglitazone to insulin aids glycemic control in type 2 diabetics Source: Reuters Industry Breifing Date: August 02, 2001
•
Glaxo's Avandia may cut cardiovascular risk by up to 30% Source: Reuters Industry Breifing Date: June 25, 2001
•
Glaxo to study effects of Avandia on cardiovascular risk Source: Reuters Industry Breifing Date: April 06, 2001
•
Rosiglitazone twice daily improves glycemic control more than once-a-day dosing Source: Reuters Industry Breifing Date: February 27, 2001
•
FDA faults SmithKline's Avandia ads Source: Reuters Industry Breifing Date: November 01, 2000
•
NICE recommends SmithKline's Avandia Source: Reuters Industry Breifing Date: August 21, 2000
•
NICE recommends Avandia for UK patients Source: Reuters Health eLine Date: August 21, 2000
•
SmithKline Beecham forecasts slow European uptake of Avandia Source: Reuters Industry Breifing Date: July 25, 2000
•
EU approves Avandia; SmithKline plans launch in UK, Germany Source: Reuters Industry Breifing Date: July 18, 2000
•
Rosiglitazone may improve beta-cell function Source: Reuters Medical News Date: June 14, 2000
•
Metformin and rosiglitazone combination effective in treating type 2 diabetes Source: Reuters Medical News Date: April 06, 2000
76
Rosiglitazone
•
FDA approves additional indication for Avandia Source: Reuters Industry Breifing Date: April 04, 2000
•
Rosiglitazone recommended for European approval Source: Reuters Medical News Date: March 17, 2000
•
Two separate cases of hepatotoxicity linked to rosiglitazone use Source: Reuters Medical News Date: January 18, 2000
•
SmithKline shares fall after EU panel decision on Avandia Source: Reuters Medical News Date: October 22, 1999
•
SmithKline refutes report of Avandia problems Source: Reuters Medical News Date: October 01, 1999
•
Rosiglitazone-metformin combination effective for type 2 diabetes Source: Reuters Medical News Date: June 24, 1999
•
SmithKline's rosiglitazone approved by FDA for type 2 diabetes Source: Reuters Medical News Date: May 27, 1999
•
FDA approves Avandia for type 2 diabetes Source: Reuters Health eLine Date: May 26, 1999
•
Bristol-Myers to co-promote SmithKline's Avandia Source: Reuters Medical News Date: April 26, 1999
•
FDA advisory panel urges approval of SmithKline's rosiglitazone Source: Reuters Medical News Date: April 23, 1999
•
Rosiglitazone for type 2 diabetes to receive priority review from FDA Source: Reuters Medical News Date: January 22, 1999
•
Rosiglitazone effectively reduces glucose levels in type 2 diabetes Source: Reuters Medical News Date: June 18, 1998 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.
Periodicals and News 77
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 “rosiglitazone” (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 “rosiglitazone” (or synonyms). If you know the name of a company that is relevant to rosiglitazone, 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/. 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 “rosiglitazone” (or synonyms).
Academic Periodicals covering Rosiglitazone Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to rosiglitazone. In addition to these sources, you can search for articles covering rosiglitazone 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
78
Rosiglitazone
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.”
79
CHAPTER 7. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.
U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for rosiglitazone. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a nonprofit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI Advice for the Patient can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with rosiglitazone. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The
80
Rosiglitazone
following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to rosiglitazone: Rosiglitazone •
Systemic - U.S. Brands: Avandia http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500022.html
Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.
Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.
81
APPENDICES
83
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 Institute11: •
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
•
National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
•
National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
•
National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25
•
National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm
•
National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
•
National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
•
National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/
11
These publications are typically written by one or more of the various NIH Institutes.
84
Rosiglitazone
•
National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm
•
National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
•
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
•
National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
•
National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
•
National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
•
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
•
National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
•
National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
•
National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
•
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
•
National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
•
National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
•
Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
•
National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
•
National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
•
Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
•
Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm
Physician Resources 85
NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.12 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:13 •
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
•
HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
•
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
•
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/
•
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
•
Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
•
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/
•
Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
•
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
•
Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
•
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
12
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). 13 See http://www.nlm.nih.gov/databases/databases.html.
86
Rosiglitazone
•
Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html
•
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 NLM Gateway14 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.15 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “rosiglitazone” (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. Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total
Items Found 832 3 140 9 1 985
HSTAT16 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.17 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.18 Simply search by “rosiglitazone” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
14
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
15
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). 16 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 17 18
The HSTAT URL is http://hstat.nlm.nih.gov/.
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.
Physician Resources 87
Coffee Break: Tutorials for Biologists19 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.20 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.21 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/.
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/.
19 Adapted 20
from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.
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. 21 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.
89
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 rosiglitazone 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 rosiglitazone. 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 rosiglitazone. 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 “rosiglitazone”:
90
Rosiglitazone
Crohn's Disease http://www.nlm.nih.gov/medlineplus/crohnsdisease.html Diabetes http://www.nlm.nih.gov/medlineplus/diabetes.html Heart Failure http://www.nlm.nih.gov/medlineplus/heartfailure.html Juvenile Diabetes http://www.nlm.nih.gov/medlineplus/juvenilediabetes.html Ovarian Cysts http://www.nlm.nih.gov/medlineplus/ovariancysts.html Ulcerative Colitis http://www.nlm.nih.gov/medlineplus/ulcerativecolitis.html 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 National Guideline Clearinghouse™ The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search this site located at http://www.guideline.gov/ by using the keyword “rosiglitazone” (or synonyms). The following was recently posted: •
Management of type 2 diabetes mellitus Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1996 March (revised 2002 Sep); 77 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3499&nbr=2725&a mp;string=rosiglitazone
•
Massachusetts guidelines for adult diabetes care Source: Massachusetts Department of Public Health, Bureau of Family and Community Health, Diabetes Control Program - State/Local Government Agency [U.S.]; 1999 June (revised 2001 Jun); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3429&nbr=2655&a mp;string=rosiglitazone
Patient Resources 91
•
The management of diabetes mellitus in the primary care setting Source: Department of Defense - Federal Government Agency [U.S.]; 1999 December; 147 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2583&nbr=1809&a mp;string=rosiglitazone
•
Type 2 diabetes practice guidelines Source: International Diabetes Center - Private Nonprofit Organization; 2000 (revised 2003); 2 pages http://www.guideline.gov/summary/summary.aspx?doc_id=4159&nbr=3187&a mp;string=rosiglitazone 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 rosiglitazone. 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
•
Family Village: http://www.familyvillage.wisc.edu/specific.htm
•
Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
•
Med Help International: http://www.medhelp.org/HealthTopics/A.html
•
Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
•
Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
•
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 rosiglitazone. By consulting all of associations listed
92
Rosiglitazone
in this chapter, you will have nearly exhausted all sources for patient associations concerned with rosiglitazone. 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 rosiglitazone. 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 “rosiglitazone” (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 “rosiglitazone”. 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 “rosiglitazone” (or synonyms) into the “For these words:” 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 “rosiglitazone” (or a synonym) into the search box, and click “Submit Query.”
93
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.22
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
22
Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.
94
Rosiglitazone
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)23: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
•
Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
•
Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
•
California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html
•
California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html
•
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
•
California: Gateway Health Library (Sutter Gould Medical Foundation)
•
California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/
•
California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
•
California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
•
California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/
•
California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/
•
California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/
•
California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html
•
California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/
•
Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/
•
Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/
•
Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/
23
Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
Finding Medical Libraries 95
•
Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml
•
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
•
Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
•
Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
•
Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
•
Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
•
Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
•
Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
•
Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
•
Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
•
Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
•
Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
•
Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
•
Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
•
Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
•
Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm
•
Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
•
Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
•
Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10
•
Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/
96
Rosiglitazone
•
Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html
•
Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
•
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
•
Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
•
Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html
•
Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
•
Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp
•
Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/
•
Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html
•
Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/
•
Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
•
Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
•
Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
•
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
•
Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330
•
Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
•
National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
•
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/
•
National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
Finding Medical Libraries 97
•
Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm
•
New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
•
New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm
•
New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm
•
New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/
•
New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
•
New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/
•
New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html
•
New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/
•
Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm
•
Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp
•
Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/
•
Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/
•
Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml
•
Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html
•
Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html
•
Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml
•
Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp
•
Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm
•
Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/
98
Rosiglitazone
•
South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp
•
Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/
•
Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/
•
Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72
99
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
•
MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
•
Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
•
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
•
On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/
•
Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp
•
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).
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
•
MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html
•
Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
•
Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
101
ROSIGLITAZONE DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 9-cis retinoic acid: A drug being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] 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 fat: Fat (adipose tissue) that is centrally distributed between the thorax and pelvis and that induces greater health risk. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] 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] 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] Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Acrylonitrile: A highly poisonous compound used widely in the manufacture of plastics, adhesives and synthetic rubber. [NIH] Acute myelogenous leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute nonlymphocytic leukemia. [NIH] Acute myeloid leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myelogenous leukemia or acute nonlymphocytic leukemia. [NIH] Acute nonlymphocytic leukemia: A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute myelogenous leukemia. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [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] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids,
102 Rosiglitazone
androgens, and glucocorticoids. [NIH] Adrenaline: A hormone. Also called epinephrine. [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] 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] Aerobic Metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, oxidative metabolism, or cell respiration. [NIH] Aerobic Respiration: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as oxidative metabolism, cell respiration, or aerobic metabolism. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [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 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] 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] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] 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]
Dictionary 103
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] Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98. [NIH] Amenorrhea: Absence of menstruation. [NIH] 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 Substitution: The naturally occurring or experimentally induced replacement of one or more amino acids in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties. [NIH] Amputation: Surgery to remove part or all of a limb or appendage. [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] 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] 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] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH] Aneurysm: A sac formed by the dilatation of the wall of an artery, a vein, or the heart. [NIH]
104 Rosiglitazone
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] 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] Anovulation: Suspension or cessation of ovulation in animals and humans. [NIH] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [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] Antidiabetic: An agent that prevents or alleviates diabetes. [EU] Antidiabetic Agent: A substance that helps a person with diabetes control the level of glucose (sugar) in the blood so that the body works as it should. [NIH] 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-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antispasmodic: An agent that relieves spasm. [EU] Anus: The opening of the rectum to the outside of the body. [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
Dictionary 105
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] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] Aqueous: Having to do with water. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arteriolar: Pertaining to or resembling arterioles. [EU] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriosclerosis: Thickening and loss of elasticity of arterial walls. Atherosclerosis is the most common form of arteriosclerosis and involves lipid deposition and thickening of the intimal cell layers within arteries. Additional forms of arteriosclerosis involve calcification of the media of muscular arteries (Monkeberg medial calcific sclerosis) and thickening of the walls of small arteries or arterioles due to cell proliferation or hyaline deposition (arteriolosclerosis). [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Ascites: Accumulation or retention of free fluid within the peritoneal cavity. [NIH] 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] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] 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] Asymptomatic: Having no signs or symptoms of disease. [NIH] 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] Autacoids: A chemically diverse group of substances produced by various tissues in the body that cause slow contraction of smooth muscle; they have other intense but varied pharmacologic activities. [NIH] Autonomic: Self-controlling; functionally independent. [EU]
106 Rosiglitazone
Axillary: Pertaining to the armpit area, including the lymph nodes that are located there. [NIH]
Axillary Artery: The continuation of the subclavian artery; it distributes over the upper limb, axilla, chest and shoulder. [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] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriostatic: 1. Inhibiting the growth or multiplication of bacteria. 2. An agent that inhibits the growth or multiplication of bacteria. [EU] Bacteriuria: The presence of bacteria in the urine with or without consequent urinary tract infection. Since bacteriuria is a clinical entity, the term does not preclude the use of urine/microbiology for technical discussions on the isolation and segregation of bacteria in the urine. [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] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]
Benzaldehyde: A colorless oily liquid used as a flavoring agent and to make dyes, perfumes, and pharmaceuticals. Benzaldehyde is chemically related to benzene. [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] Beta-pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Bezafibrate: Antilipemic agent that lowers cholesterol and triglycerides. It decreases low density lipoproteins and increases high density lipoproteins. [NIH] Bilateral: Affecting both the right and left side of body. [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] Bilirubin: A bile pigment that is a degradation product of heme. [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] 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] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH]
Dictionary 107
Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived 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] Bladder: The organ that stores urine. [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] Body Composition: The relative amounts of various components in the body, such as percent body fat. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Body Mass Index: One of the anthropometric measures of body mass; it has the highest correlation with skinfold thickness or body density. [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] 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] Brachial: All the nerves from the arm are ripped from the spinal cord. [NIH] Brachial Artery: The continuation of the axillary artery; it branches into the radial and ulnar arteries. [NIH]
108 Rosiglitazone
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]
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] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [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] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capillary Permeability: Property of blood capillary walls that allows for the selective exchange of substances. Small lipid-soluble molecules such as carbon dioxide and oxygen move freely by diffusion. Water and water-soluble molecules cannot pass through the endothelial walls and are dependent on microscopic pores. These pores show narrow areas (tight junctions) which may limit large molecule movement. [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 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] 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 Output: The volume of blood passing through the heart per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with stroke volume (volume per beat). [NIH] 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
Dictionary 109
can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Carnitine: Constituent of striated muscle and liver. It is used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Caspases: A family of intracellular cysteine endopeptidases. They play a key role in inflammation and mammalian apoptosis. They are specific for aspartic acid at the P1 position. They are divided into two classes based on the lengths of their N-terminal prodomains. Caspases-1,-2,-4,-5,-8, and -10 have long prodomains and -3,-6,-7,-9 have short prodomains. EC 3.4.22.-. [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] Causal: Pertaining to a cause; directed against a cause. [EU] Celecoxib: A drug that reduces pain. Celecoxib belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is being studied for cancer prevention. [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 Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter 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 Division: The fission of a cell. [NIH] 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] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [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]
110 Rosiglitazone
Chemoprevention: The use of drugs, vitamins, or other agents to try to reduce the risk of, or delay the development or recurrence of, cancer. [NIH] Chemopreventive: Natural or synthetic compound used to intervene in the early precancerous stages of carcinogenesis. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotherapy: Treatment with anticancer drugs. [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] 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] 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] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Obstructive Pulmonary Disease: Collective term for chronic bronchitis and emphysema. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [NIH] Cirrhosis: A type of chronic, progressive liver disease. [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] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [NIH] Claudication: Limping or lameness. [EU] 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] Clomiphene: A stilbene derivative that functions both as a partial estrogen agonist and complete estrogen antagonist depending on the target tissue. It antagonizes the estrogen receptor thereby initiating or augmenting ovulation in anovulatory women. [NIH]
Dictionary 111
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] Clot Retraction: Retraction of a clot resulting from contraction of platelet pseudopods attached to fibrin strands that is dependent on the contractile protein thrombosthenin. Used as a measure of platelet function. [NIH] Cod Liver Oil: Oil obtained from fresh livers of the cod family, Gadidae. It is a source of vitamins A and D. [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] Colitis: Inflammation of the colon. [NIH] 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] 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] Complement Activation: The sequential activation of serum components C1 through C9, initiated by an erythrocyte-antibody complex or by microbial polysaccharides and
112 Rosiglitazone
properdin, and producing an inflammatory response. [NIH] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [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] Concomitant: Accompanying; accessory; joined with another. [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] 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 tissue cells embedded in a large amount of extracellular matrix. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constrict: Tighten; narrow. [NIH] Constriction: The act of constricting. [NIH] Consumption: Pulmonary tuberculosis. [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]
Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [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]
Dictionary 113
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 Disease: Disorder of cardiac function due to an imbalance between myocardial function and the capacity of the coronary vessels to supply sufficient flow for normal function. It is a form of myocardial ischemia (insufficient blood supply to the heart muscle) caused by a decreased capacity of the coronary vessels. [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] Coronary Vessels: The veins and arteries of the heart. [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] 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] Curative: Tending to overcome disease and promote recovery. [EU] 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] Cyproterone: An anti-androgen that, in the form of its acetate, also has progestational properties. It is used in the treatment of hypersexuality in males, as a palliative in prostatic carcinoma, and, in combination with estrogen, for the therapy of severe acne and hirsutism in females. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cysteine Endopeptidases: Endopeptidases which have a cysteine involved in the catalytic process. This group of enzymes is inactivated by sulfhydryl reagents. EC 3.4.22. [NIH] 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]
114 Rosiglitazone
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] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] De novo: In cancer, the first occurrence of cancer in the body. [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] Delivery of Health Care: The concept concerned with all aspects of providing and distributing health services to a patient population. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [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] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diastolic: Of or pertaining to the diastole. [EU] 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] Dihydrotestosterone: Anabolic agent. [NIH] Dilatation: The act of dilating. [NIH] Dilatation, Pathologic: The condition of an anatomical structure's being dilated beyond normal dimensions. [NIH] Dilate: Relax; expand. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Dilator: A device used to stretch or enlarge an opening. [NIH] Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer. [NIH]
Dictionary 115
Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disposition: A tendency either physical or mental toward certain diseases. [EU] 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 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] 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] 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] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [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] 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] Dyslipidemia: Disorders in the lipoprotein metabolism; classified as hypercholesterolemia, hypertriglyceridemia, combined hyperlipidemia, and low levels of high-density lipoprotein (HDL) cholesterol. All of the dyslipidemias can be primary or secondary. Both elevated levels of low-density lipoprotein (LDL) cholesterol and low levels of HDL cholesterol predispose to premature atherosclerosis. [NIH] Dysuria: Painful or difficult urination. [EU] Echocardiography: Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic. [NIH]
116 Rosiglitazone
Eclampsia: Onset of convulsions or coma in a previously diagnosed pre-eclamptic patient. [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] Elastin: The protein that gives flexibility to tissues. [NIH] Electrocardiogram: Measurement of electrical activity during heartbeats. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]
Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emphysema: A pathological accumulation of air in tissues or organs. [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] Endocrinology: A subspecialty of internal medicine concerned with the metabolism, physiology, and disorders of the endocrine system. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endometrial: Having to do with the endometrium (the layer of tissue that lines the uterus). [NIH]
Endometrium: The layer of tissue that lines the uterus. [NIH] Endopeptidases: A subclass of peptide hydrolases. They are classified primarily by their catalytic mechanism. Specificity is used only for identification of individual enzymes. They comprise the serine endopeptidases, EC 3.4.21; cysteine endopeptidases, EC 3.4.22; aspartic endopeptidases, EC 3.4.23, metalloendopeptidases, EC 3.4.24; and a group of enzymes yet to be assigned to any of the above sub-classes, EC 3.4.99. EC 3.4.-. [NIH]
Dictionary 117
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] Endotoxemia: A condition characterized by the presence of endotoxins in the blood. If endotoxemia is the result of gram-negative rod-shaped bacteria, shock may occur. [NIH] Endotoxic: Of, relating to, or acting as an endotoxin (= a heat-stable toxin, associated with the outer membranes of certain gram-negative bacteria. Endotoxins are not secreted and are released only when the cells are disrupted). [EU] Endotoxin: Toxin from cell walls of bacteria. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] 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] Enhancer: Transcriptional element in the virus genome. [NIH] 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]
Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] 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] Epigastric: Having to do with the upper middle area of the abdomen. [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]
118 Rosiglitazone
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] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythromycin: A bacteriostatic antibiotic substance produced by Streptomyces erythreus. Erythromycin A is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50S ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins. [NIH] Erythropoiesis: The production of erythrocytes. [EU] Escalation: Progressive use of more harmful drugs. [NIH] Esophagitis: Inflammation, acute or chronic, of the esophagus caused by bacteria, chemicals, or trauma. [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]
Estrone: 3-Hydroxyestra-1,3,5(10)-trien-17-one. A metabolite of estradiol but possessing less biological activity. It is found in the urine of pregnant women and mares, in the human placenta, and in the urine of bulls and stallions. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), estrone may reasonably be anticipated to be a carcinogen (Merck, 11th ed). [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] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evacuation: An emptying, as of the bowels. [EU] Exercise Test: Controlled physical activity, more strenuous than at rest, which is performed in order to allow assessment of physiological functions, particularly cardiovascular and pulmonary, but also aerobic capacity. Maximal (most intense) exercise is usually required but submaximal exercise is also used. The intensity of exercise is often graded, using criteria such as rate of work done, oxygen consumption, and heart rate. Physiological data obtained from an exercise test may be used for diagnosis, prognosis, and evaluation of disease severity, and to evaluate therapy. Data may also be used in prescribing exercise by determining a person's exercise capacity. [NIH] Exercise Therapy: Motion of the body or its parts to relieve symptoms or to improve function, leading to physical fitness, but not physical education and training. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Extracellular: Outside a cell or cells. [EU]
Dictionary 119
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] Extrapyramidal: Outside of the pyramidal tracts. [EU] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [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] Fatty Liver: The buildup of fat in liver cells. The most common cause is alcoholism. Other causes include obesity, diabetes, and pregnancy. Also called steatosis. [NIH] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [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] Fibrinolytic: Pertaining to, characterized by, or causing the dissolution of fibrin by enzymatic action [EU] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fistula: Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. [NIH] Flavoxate: A drug that has been used in various urinary syndromes and as an antispasmodic. Its therapeutic usefulness and its mechanism of action are not clear. It may have local anesthetic activity and direct relaxing effects on smooth muscle as well as some activity as a muscarinic antagonist. [NIH]
120 Rosiglitazone
Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Flutamide: An antiandrogen with about the same potency as cyproterone in rodent and canine species. [NIH] Forearm: The part between the elbow and the wrist. [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] 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] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
Gastritis: Inflammation of the stomach. [EU] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [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]
Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Genetic Markers: A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genomics: The systematic study of the complete DNA sequences (genome) of organisms. [NIH]
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] 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] 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 Clamp Technique: Maintenance of a constant blood glucose level by perfusion or infusion with glucose or insulin. It is used for the study of metabolic rates (e.g., in glucose,
Dictionary 121
lipid, amino acid metabolism) at constant glucose concentration. [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] Glucose tolerance: The power of the normal liver to absorb and store large quantities of glucose and the effectiveness of intestinal absorption of glucose. The glucose tolerance test is a metabolic test of carbohydrate tolerance that measures active insulin, a hepatic function based on the ability of the liver to absorb glucose. The test consists of ingesting 100 grams of glucose into a fasting stomach; blood sugar should return to normal in 2 to 21 hours after ingestion. [NIH] Glucose Tolerance Test: Determination of whole blood or plasma sugar in a fasting state before and at prescribed intervals (usually 1/2 hr, 1 hr, 3 hr, 4 hr) after taking a specified amount (usually 100 gm orally) of glucose. [NIH] Glyburide: An antidiabetic sulfonylurea derivative with actions similar to those of chlorpropamide. [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] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Gonadal: Pertaining to a gonad. [EU] Gonadorelin: A decapeptide hormone released by the hypothalamus. It stimulates the synthesis and secretion of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary gland. [NIH] Gonadotropin: The water-soluble follicle stimulating substance, by some believed to originate in chorionic tissue, obtained from the serum of pregnant mares. It is used to supplement the action of estrogens. [NIH] Gonads: The gamete-producing glands, ovary or testis. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [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] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] 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] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [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
122 Rosiglitazone
disease process are referred to as headache disorders (e.g., migraine). [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 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 Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [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 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] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatitis C: A form of hepatitis, similar to type B post-transfusion hepatitis, but caused by a virus which is serologically distinct from the agents of hepatitis A, B, and E, and which may persist in the blood of chronic asymptomatic carriers. Hepatitis C is parenterally transmitted and associated with transfusions and drug abuse. [NIH] Hepatocellular: Pertaining to or affecting liver cells. [EU] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Hepatoma: A liver tumor. [NIH] Hepatotoxic: Toxic to liver cells. [EU] Hepatotoxicity: How much damage a medicine or other substance does to the liver. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring.
Dictionary 123
2. The genetic constitution of an individual. [EU] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]
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] Hirsutism: Excess hair in females and children with an adult male pattern of distribution. The concept does not include hypertrichosis, which is localized or generalized excess hair. [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] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormonal therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called hormone therapy or endocrine therapy. [NIH] 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] Hormone therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called endocrine therapy. [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] 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] 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] Hyperandrogenism: A state characterized or caused by an excessive secretion of androgens by the adrenal cortex, ovaries, or testes. The clinical significance in males is negligible, so the term is used most commonly with reference to the female. The common manifestations in women are hirsutism and virilism. It is often caused by ovarian disease (particularly the polycystic ovary syndrome) and by adrenal diseases (particularly adrenal gland hyperfunction). [NIH] Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [NIH] Hyperglycaemia: Abnormally increased content of sugar in the blood. [EU] Hyperglycemia: Abnormally high blood sugar. [NIH]
124 Rosiglitazone
Hyperlipidemia: An excess of lipids in the blood. [NIH] Hyperlipoproteinemia: Metabolic disease characterized by elevated plasma cholesterol and/or triglyceride levels. The inherited form is attributed to a single gene mechanism. [NIH] Hyperphagia: Ingestion of a greater than optimal quantity of food. [NIH] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hypersecretion: Excessive secretion. [EU] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypertriglyceridemia: Condition of elevated triglyceride concentration in the blood; an inherited form occurs in familial hyperlipoproteinemia IIb and hyperlipoproteinemia type IV. It has been linked to higher risk of heart disease and arteriosclerosis. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hypoglycemic: An orally active drug that produces a fall in blood glucose concentration. [NIH]
Hypoglycemic Agents: Agents which lower the blood glucose level. [NIH] Hypogonadism: Condition resulting from or characterized by abnormally decreased functional activity of the gonads, with retardation of growth and sexual development. [NIH] Hypolipidemic: A drug that lowers abnormally high plasma concentrations of cholesterol or triglycerides or both. [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] Ibuprofen: A nonsteroidal anti-inflammatory agent with analgesic properties used in the therapy of rheumatism and arthritis. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Ileum: The lower end of the small intestine. [NIH] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [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
Immunogenic: Producing immunity; evoking an immune response. [EU] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunology: The study of the body's immune system. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU]
Dictionary 125
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] 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] Indinavir: A potent and specific HIV protease inhibitor that appears to have good oral bioavailability. [NIH] Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes. [NIH] 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] Infantile: Pertaining to an infant or to infancy. [EU] 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]
Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] 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] Inlay: In dentistry, a filling first made to correspond with the form of a dental cavity and then cemented into the cavity. [NIH] Inositol: An isomer of glucose that has traditionally been considered to be a B vitamin
126 Rosiglitazone
although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction. [NIH] Inotropic: Affecting the force or energy of muscular contractions. [EU] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [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] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Intermittent Claudication: A symptom complex characterized by leg pain and weakness brought on by walking, with the disappearance of the symptoms following a brief rest. [NIH] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Intervention Studies: Epidemiologic investigations designed to test a hypothesized causeeffect relation by modifying the supposed causal factor(s) in the study population. [NIH] 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] Intracellular: Inside a cell. [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]
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] Irritable Bowel Syndrome: A disorder that comes and goes. Nerves that control the muscles in the GI tract are too active. The GI tract becomes sensitive to food, stool, gas, and stress. Causes abdominal pain, bloating, and constipation or diarrhea. Also called spastic colon or mucous colitis. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Islet: Cell producing insulin in pancreas. [NIH] Kallidin: A decapeptide bradykinin homolog produced by the action of tissue and glandular kallikreins on low-molecular-weight kininogen. It is a smooth-muscle stimulant and hypotensive agent that functions through vasodilatation. [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]
Dictionary 127
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] Kidney Failure: The inability of a kidney to excrete metabolites at normal plasma levels under conditions of normal loading, or the inability to retain electrolytes under conditions of normal intake. In the acute form (kidney failure, acute), it is marked by uremia and usually by oliguria or anuria, with hyperkalemia and pulmonary edema. The chronic form (kidney failure, chronic) is irreversible and requires hemodialysis. [NIH] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] 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] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] 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] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leuprolide: A potent and long acting analog of naturally occurring gonadotropin-releasing hormone (gonadorelin). Its action is similar to gonadorelin, which regulates the synthesis and release of pituitary gonadotropins. [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] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] Ligation: Application of a ligature to tie a vessel or strangulate a part. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together
128 Rosiglitazone
from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipase: An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. It is produced by glands on the tongue and by the pancreas and initiates the digestion of dietary fats. (From Dorland, 27th ed) EC 3.1.1.3. [NIH] Lipid: Fat. [NIH] Lipid A: Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties. [NIH] Lipodystrophy: A collection of rare conditions resulting from defective fat metabolism and characterized by atrophy of the subcutaneous fat. They include total, congenital or acquired, partial, abdominal infantile, and localized lipodystrophy. [NIH] Lipolysis: The hydrolysis of lipids. [NIH] Lipophilic: Having an affinity for fat; pertaining to or characterized by lipophilia. [EU] Lipopolysaccharides: 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, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Lipoprotein Lipase: An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. The enzyme hydrolyzes triacylglycerols in chylomicrons, very-low-density lipoproteins, low-density lipoproteins, and diacylglycerols. It occurs on capillary endothelial surfaces, especially in mammary, muscle, and adipose tissue. Genetic deficiency of the enzyme causes familial hyperlipoproteinemia Type I. (Dorland, 27th ed) EC 3.1.1.34. [NIH] Lipoprotein(a): A family of lipoprotein particles varying in density and size depending on the protein-lipid ratio and the protein composition. These particles consist of apolipoprotein B-100 covalently linked to apolipoprotein-a by one or two disulfide bonds. There is a correlation between high plasma levels of this lipoprotein and increased risk for atherosclerotic cardiovascular disease. [NIH] Liposarcoma: A rare cancer of the fat cells. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [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] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lumbar puncture: A procedure in which a needle is put into the lower part of the spinal column to collect cerebrospinal fluid or to give anticancer drugs intrathecally. Also called a spinal tap. [NIH]
Dictionary 129
Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [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] Lymphocytes: White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each); those with characteristics of neither major class are called null cells. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [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] 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] Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] 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]
Mammary: Pertaining to the mamma, or breast. [EU] 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] 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] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] 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] Membrane: A very thin layer of tissue that covers a surface. [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]
130 Rosiglitazone
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 producing either distress or impairment of function. [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [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] 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] Microdialysis: A technique for measuring extracellular concentrations of substances in tissues, usually in vivo, by means of a small probe equipped with a semipermeable membrane. Substances may also be introduced into the extracellular space through the membrane. [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 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] Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Midaxillary line: An imaginary vertical line that passes midway between the anterior and posterior axillary (armpit) folds. [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] Millimeter: A measure of length. A millimeter is approximately 26-times smaller than an inch. [NIH] Mineralization: The action of mineralizing; the state of being mineralized. [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] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Modification: A change in an organism, or in a process in an organism, that is acquired
Dictionary 131
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] 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] Monoamine: Enzyme that breaks down dopamine in the astrocytes and microglia. [NIH] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Mononuclear: A cell with one nucleus. [NIH] Monotherapy: A therapy which uses only one drug. [EU] Motility: The ability to move spontaneously. [EU] 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] Multicenter study: A clinical trial that is carried out at more than one medical institution. [NIH]
Myocardial Ischemia: A disorder of cardiac function caused by insufficient blood flow to 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] Natriuresis: The excretion of abnormal amounts of sodium in the urine. [EU] 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] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [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] Nephropathy: Disease of the kidneys. [EU]
132 Rosiglitazone
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] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [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] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neurotransmitters: Endogenous signaling molecules that alter the behavior of neurons or effector cells. Neurotransmitter is used here in its most general sense, including not only messengers that act directly to regulate ion channels, but also those that act through second messenger systems, and those that act at a distance from their site of release. Included are neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not acting at synapses. [NIH] Neutropenia: An abnormal decrease in the number of neutrophils, a type of white blood cell. [NIH] Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. [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 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. 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] 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] Nitroprusside: (OC-6-22)-Pentakis(cyano-C)nitrosoferrate(2-). A powerful vasodilator used in emergencies to lower blood pressure or to improve cardiac function. It is also an indicator for free sulfhydryl groups in proteins. [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]
Dictionary 133
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] 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] Nutritional Status: State of the body in relation to the consumption and utilization of nutrients. [NIH] Octreotide: A potent, long-acting somatostatin octapeptide analog which has a wide range of physiological actions. It inhibits growth hormone secretion, is effective in the treatment of hormone-secreting tumors from various organs, and has beneficial effects in the management of many pathological states including diabetes mellitus, orthostatic hypertension, hyperinsulinism, hypergastrinemia, and small bowel fistula. [NIH] Oedema: The presence of abnormally large amounts of fluid in the intercellular tissue spaces of the body; usually applied to demonstrable accumulation of excessive fluid in the subcutaneous tissues. Edema may be localized, due to venous or lymphatic obstruction or to increased vascular permeability, or it may be systemic due to heart failure or renal disease. Collections of edema fluid are designated according to the site, e.g. ascites (peritoneal cavity), hydrothorax (pleural cavity), and hydropericardium (pericardial sac). Massive generalized edema is called anasarca. [EU] Oligomenorrhea: Abnormally infrequent menstruation. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Orlistat: A lipase inhibitor used for weight loss. Lipase is an enzyme found in the bowel that assists in lipid absorption by the body. Orlistat blocks this enzyme, reducing the amount of fat the body absorbs by about 30 percent. It is known colloquially as a "fat blocker." Because more oily fat is left in the bowel to be excreted, Orlistat can cause an oily anal leakage and fecal incontinence. Orlistat may not be suitable for people with bowel conditions such as irritable bowel syndrome or Crohn's disease. [NIH] Orthostatic: Pertaining to or caused by standing erect. [EU] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a 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] Ossification: The formation of bone or of a bony substance; the conversion of fibrous tissue or of cartilage into bone or a bony substance. [EU] Osteogenesis: The histogenesis of bone including ossification. It occurs continuously but particularly in the embryo and child and during fracture repair. [NIH] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal
134 Rosiglitazone
osteoporosis and age-related (or senile) osteoporosis. [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] Overweight: An excess of body weight but not necessarily body fat; a body mass index of 25 to 29.9 kg/m2. [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] 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 metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, cell respiration, or aerobic metabolism. [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Paclitaxel: Antineoplastic agent isolated from the bark of the Pacific yew tree, Taxus brevifolia. Paclitaxel stabilizes microtubules in their polymerized form and thus mimics the action of the proto-oncogene proteins c-mos. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] 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] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Particle: A tiny mass of material. [EU] 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] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Pelvic: Pertaining to the pelvis. [EU]
Dictionary 135
Peptic: Pertaining to pepsin or to digestion; related to the action of gastric juices. [EU] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] 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] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Petrolatum: A colloidal system of semisolid hydrocarbons obtained from petroleum. It is used as an ointment base, topical protectant, and lubricant. [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] Pharmacogenetics: A branch of genetics which deals with the genetic components of variability in individual responses to and metabolism (biotransformation) of drugs. [NIH] 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] Phenolphthalein: An acid-base indicator which is colorless in acid solution, but turns pink to red as the solution becomes alkaline. It is used medicinally as a cathartic. [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] 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] Phosphorylated: Attached to a phosphate group. [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] Physical Fitness: A state of well-being in which performance is optimal, often as a result of physical conditioning which may be prescribed for disease therapy. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase
136 Rosiglitazone
"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] Pilot study: The initial study examining a new method or treatment. [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] 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] 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 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] 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] Plethysmography: Recording of change in the size of a part as modified by the circulation in it. [NIH] Pleural: A circumscribed area of hyaline whorled fibrous tissue which appears on the surface of the parietal pleura, on the fibrous part of the diaphragm or on the pleura in the interlobar fissures. [NIH] Pleural cavity: A space enclosed by the pleura (thin tissue covering the lungs and lining the interior wall of the chest cavity). It is bound by thin membranes. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH]
Dictionary 137
Polycystic Ovary Syndrome: Clinical symptom complex characterized by oligomenorrhea or amenorrhea, anovulation, and regularly associated with bilateral polycystic ovaries. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] 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] Postprandial: Occurring after dinner, or after a meal; postcibal. [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] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [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] Pravastatin: An antilipemic fungal metabolite isolated from cultures of Nocardia autotrophica. It acts as a competitive inhibitor of HMG CoA reductase (hydroxymethylglutaryl CoA reductases). [NIH] Precancerous: A term used to describe a condition that may (or is likely to) become cancer. Also called premalignant. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] 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 symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Pre-Eclampsia: Development of hypertension with proteinuria, edema, or both, due to pregnancy or the influence of a recent pregnancy. It occurs after the 20th week of gestation, but it may develop before this time in the presence of trophoblastic disease. [NIH] Pre-eclamptic: A syndrome characterized by hypertension, albuminuria, and generalized oedema, occurring only in pregnancy. [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 endpoint: The main result that is measured at the end of a study to see if a given treatment worked (e.g., the number of deaths or the difference in survival between the treatment group and the control group). What the primary endpoint will be is decided
138 Rosiglitazone
before the study begins. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [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] Progressive disease: Cancer that is increasing in scope or severity. [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] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Promotor: In an operon, a nucleotide sequence located at the operator end which contains all the signals for the correct initiation of genetic transcription by the RNA polymerase holoenzyme and determines the maximal rate of RNA synthesis. [NIH] Promyelocytic leukemia: A type of acute myeloid leukemia, a quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. [NIH]
Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandins: A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes. [NIH] 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] Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (endopeptidases). [NIH] 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]
Dictionary 139
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] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] 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] Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity. [NIH] Proto-Oncogene Proteins c-mos: Cellular proteins encoded by the c-mos genes. They function in the cell cycle to maintain maturation promoting factor in the active state and have protein-serine/threonine kinase activity. Oncogenic transformation can take place when c-mos proteins are expressed at the wrong time. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Psychic: Pertaining to the psyche or to the mind; mental. [EU] 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] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]
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] 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]
Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [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
140 Rosiglitazone
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] Radioactive: Giving off radiation. [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] Ranitidine: A non-imidazole blocker of those histamine receptors that mediate gastric secretion (H2 receptors). It is used to treat gastrointestinal ulcers. [NIH] Reabsorption: 1. The act or process of absorbing again, as the selective absorption by the kidneys of substances (glucose, proteins, sodium, etc.) already secreted into the renal tubules, and their return to the circulating blood. 2. Resorption. [EU] 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, 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] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [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] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflux: The term used when liquid backs up into the esophagus from the stomach. [NIH] Refractory: Not readily yielding to treatment. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] 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] Respirable: Dust particles smaller than 0. 005 mm, which are deposited in the respiratory region of the lungs. [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] Response Elements: Nucleotide sequences, usually upstream, which are recognized by specific regulatory transcription factors, thereby causing gene response to various regulatory agents. These elements may be found in both promotor and enhancer regions. [NIH]
Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH]
Dictionary 141
Retinoid: Vitamin A or a vitamin A-like compound. [NIH] Retrospective: Looking back at events that have already taken place. [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] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rod: A reception for vision, located in the retina. [NIH] Rosiglitazone: A drug taken to help reduce the amount of sugar in the blood. Rosiglitazone helps make insulin more effective and improves regulation of blood sugar. It belongs to the family of drugs called thiazolidinediones. [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] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Sarcoma: A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Second cancer: Refers to a new primary cancer that is caused by previous cancer treatment, or a new primary cancer in a person with a history of cancer. [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] Sedentary: 1. Sitting habitually; of inactive habits. 2. Pertaining to a sitting posture. [EU] Sediment: A precipitate, especially one that is formed spontaneously. [EU] 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] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Septal: An abscess occurring at the root of the tooth on the proximal surface. [NIH] Septum: A dividing wall or partition; a general term for such a structure. The term is often used alone to refer to the septal area or to the septum pellucidum. [EU] Septum Pellucidum: A triangular double membrane separating the anterior horns of the lateral ventricles of the brain. It is situated in the median plane and bounded by the corpus callosum and the body and columns of the fornix. [NIH]
142 Rosiglitazone
Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] 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] 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] 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]
Sibutramine: A drug used for the management of obesity that helps reduce food intake and is indicated for weight loss and maintenance of weight loss when used in conjunction with a reduced-calorie diet. It works to suppress the appetite primarily by inhibiting the reuptake of the neurotransmitters norepinephrine and serotonin. Side effects include dry mouth, headache, constipation, insomnia, and a slight increase in average blood pressure. In some patients it causes a higher blood pressure increase. [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] Sigmoidoscopy: Endoscopic examination, therapy or surgery of the sigmoid flexure. [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]
Dictionary 143
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] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]
Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [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] Soft tissue sarcoma: A sarcoma that begins in the muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [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] Somatostatin: A polypeptide hormone produced in the hypothalamus, and other tissues and organs. It inhibits the release of human growth hormone, and also modulates important physiological functions of the kidney, pancreas, and gastrointestinal tract. Somatostatin receptors are widely expressed throughout the body. Somatostatin also acts as a neurotransmitter in the central and peripheral nervous systems. [NIH] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [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] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Sperm: The fecundating fluid of the male. [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] Spinal tap: A procedure in which a needle is put into the lower part of the spinal column to collect cerebrospinal fluid or to give anticancer drugs intrathecally. Also called a lumbar
144 Rosiglitazone
puncture. [NIH] Spinous: Like a spine or thorn in shape; having spines. [NIH] Stabilization: The creation of a stable state. [EU] Stabilizer: A device for maintaining constant X-ray tube voltage or current. [NIH] Standard therapy: A currently accepted and widely used treatment for a certain type of cancer, based on the results of past research. [NIH] Steatosis: Fatty degeneration. [EU] Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] 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] Stimulants: Any drug or agent which causes stimulation. [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] 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] 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] Stroke Volume: The amount of blood pumped out of the heart per beat not to be confused with cardiac output (volume/time). [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Styrene: A colorless, toxic liquid with a strong aromatic odor. It is used to make rubbers, polymers and copolymers, and polystyrene plastics. [NIH] Subacute: Somewhat acute; between acute and chronic. [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] 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
Dictionary 145
peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]
Substrate: A substance upon which an enzyme acts. [EU] Sucralfate: A basic aluminum complex of sulfated sucrose. It is advocated in the therapy of peptic, duodenal, and prepyloric ulcers, gastritis, reflux esophagitis, and other gastrointestinal irritations. It acts primarily at the ulcer site, where it has cytoprotective, pepsinostatic, antacid, and bile acid-binding properties. The drug is only slightly absorbed by the digestive mucosa, which explains the absence of systemic effects and toxicity. [NIH] Suppositories: A small cone-shaped medicament having cocoa butter or gelatin at its basis and usually intended for the treatment of local conditions in the rectum. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [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] Systemic: Affecting the entire body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] 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] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] 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] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [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] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a
146 Rosiglitazone
specific function. [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] 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] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Traction: The act of pulling. [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfusion: The infusion of components of blood or whole blood into the bloodstream. The blood may be donated from another person, or it may have been taken from the person earlier and stored until needed. [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] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Trees: Woody, usually tall, perennial higher plants (Angiosperms, Gymnosperms, and some Pterophyta) having usually a main stem and numerous branches. [NIH] 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] Troglitazone: A drug used in diabetes treatment that is being studied for its effect on reducing the risk of cancer cell growth in fat tissue. [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] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other
Dictionary 147
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] 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] 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] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [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] Ultrasonography: The visualization of deep structures of the body by recording the reflections of echoes of pulses of ultrasonic waves directed into the tissues. Use of ultrasound for imaging or diagnostic purposes employs frequencies ranging from 1.6 to 10 megahertz. [NIH] Ultrasound test: A test that bounces sound waves off tissues and internal organs and changes the echoes into pictures (sonograms). [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]
Urinalysis: Examination of urine by chemical, physical, or microscopic means. Routine urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [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] 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] 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] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasoactive: Exerting an effect upon the calibre of blood vessels. [EU] Vasodilation: Physiological dilation of the blood vessels without anatomic change. For dilation with anatomic change, dilatation, pathologic or aneurysm (or specific aneurysm) is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] 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
148 Rosiglitazone
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] Ventricular Dysfunction: A condition in which the ventricles of the heart exhibit a decreased functionality. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Vinca Alkaloids: A class of alkaloids from the genus of apocyanaceous woody herbs including periwinkles. They are some of the most useful antineoplastic agents. [NIH] Vinorelbine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virilism: Development of masculine traits in the female. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or 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 fat: One of the three compartments of abdominal fat. Retroperitoneal and subcutaneous are the other two compartments. [NIH] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called retinoids. [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] Waist circumference: To define the level at which the waist circumference is measured, a bony landmark is first located and marked. The subject stands, and the technician, positioned to the right of the subject, palpates the upper hip bone to locate the right ileum. Just above the uppermost lateral border of the right ileum, a horizontal mark is drawn and then crossed with a vertical mark on the midaxillary line. The measuring tape is then placed around the trunk, at the level of the mark on the right side, making sure that it is on a level horizontal plane on all sides. The tape is then tightened slightly without compressing the skin and underlying subcutaneous tissues. The measure is recorded in centimeters to the nearest millimeter. [NIH] Weight Gain: Increase in body weight over existing weight. [NIH] Weight Lifting: A sport in which weights are lifted competitively or as an exercise. [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]
Wound Healing: Restoration of integrity to traumatized tissue. [NIH]
Dictionary 149
Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [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]
151
INDEX 9 9-cis retinoic acid, 15, 101 A Abdomen, 58, 61, 101, 107, 117, 126, 128, 135, 144, 145 Abdominal, 11, 44, 58, 101, 126, 128, 134, 135, 147, 148 Abdominal fat, 58, 101, 148 Abdominal Pain, 11, 101, 126, 147 Aberrant, 20, 101 Acceptor, 101, 134 Acetylcholine, 60, 101, 132 Acne, 24, 101, 113 Acrylonitrile, 101, 141 Acute myelogenous leukemia, 101 Acute myeloid leukemia, 21, 101, 138 Acute nonlymphocytic leukemia, 101 Adaptability, 101, 109 Adipocytes, 14, 15, 32, 36, 39, 40, 41, 44, 53, 101, 127 Adipose Tissue, 7, 8, 19, 25, 32, 37, 60, 101, 128, 145 Adjuvant, 101, 120 Adrenal Cortex, 101, 113, 118, 123, 138 Adrenaline, 68, 102 Adrenergic, 102, 115, 117, 145 Adverse Effect, 102, 142 Aerobic, 60, 102, 118, 134 Aerobic Metabolism, 102, 134 Aerobic Respiration, 102, 134 Aerosol, 64, 67, 102 Afferent, 102, 127 Affinity, 23, 36, 102, 105, 128, 143 Age of Onset, 102, 147 Agonist, 6, 8, 14, 22, 46, 48, 49, 53, 67, 68, 102, 110, 115 Albumin, 45, 102, 136 Algorithms, 102, 107 Alkaline, 38, 102, 108, 135 Alkaline Phosphatase, 38, 102 Alternative medicine, 77, 103 Aluminum, 103, 145 Amenorrhea, 103, 137 Amino acid, 19, 64, 103, 104, 105, 113, 118, 121, 123, 135, 137, 138, 139, 142, 144, 145, 146, 147 Amino Acid Substitution, 19, 103 Amputation, 13, 103
Amyloid, 15, 103 Anaesthesia, 103, 125 Anal, 103, 133 Analgesic, 103, 124 Analog, 103, 127, 133 Analogous, 103, 146 Anaphylatoxins, 103, 111 Anatomical, 103, 110, 114, 124 Androgens, 5, 24, 102, 103, 123 Aneurysm, 103, 147 Angina, 104, 132 Anginal, 104, 132 Angiogenesis, 104, 129 Animal model, 7, 26, 104 Anions, 102, 104, 126 Anovulation, 24, 104, 137 Antibiotic, 104, 118 Antibodies, 104, 121, 124 Antibody, 102, 104, 111, 121, 125, 129, 143 Anticholinergic, 67, 104 Antidiabetic, 4, 28, 30, 65, 66, 68, 104, 121 Antidiabetic Agent, 28, 66, 68, 104 Antigen, 102, 104, 111, 125, 129 Antigen-Antibody Complex, 104, 111 Anti-inflammatory, 16, 20, 40, 104, 109, 124, 125 Anti-Inflammatory Agents, 16, 104, 109 Antispasmodic, 104, 119 Anus, 103, 104, 107, 111 Apolipoproteins, 104, 128 Apoptosis, 21, 49, 104, 109 Applicability, 22, 105 Aqueous, 64, 105, 106, 114, 116 Arginine, 103, 105, 132 Arterial, 13, 105, 110, 124, 132, 139, 145 Arteries, 32, 105, 107, 113, 128, 130, 131 Arteriolar, 105, 108 Arterioles, 105, 107, 108, 131 Arteriosclerosis, 30, 41, 105, 124, 131 Artery, 30, 33, 49, 58, 60, 103, 105, 106, 113, 139 Ascites, 105, 133 Aspartic, 105, 109, 116 Aspartic Acid, 105, 109 Assay, 18, 105 Astrocytes, 105, 131 Asymptomatic, 105, 122 Atrophy, 105, 128
152 Rosiglitazone
Autacoids, 105, 125 Autonomic, 101, 105, 132 Axillary, 106, 107, 130 Axillary Artery, 106, 107 B Bacteria, 104, 106, 112, 117, 118, 119, 121, 130, 147 Bactericidal, 106, 118 Bacteriostatic, 106, 118 Bacteriuria, 106, 147 Base, 18, 65, 106, 114, 126, 135, 145 Benign, 11, 106, 121, 131 Benzaldehyde, 65, 106 Benzene, 106 Beta-pleated, 103, 106 Bezafibrate, 68, 106 Bilateral, 106, 137 Bile, 106, 120, 128, 144, 145 Bilirubin, 102, 106 Binding Sites, 36, 106 Bioavailability, 7, 106, 125 Biochemical, 9, 40, 46, 61, 106, 142 Biomarkers, 7, 106 Biopsy, 6, 12, 106 Biosynthesis, 107, 138, 142 Biotechnology, 27, 77, 85, 107 Biotransformation, 26, 107, 135 Biphasic, 29, 107 Bladder, 107, 125, 138, 147 Blood Glucose, 3, 19, 65, 71, 107, 120, 122, 124, 126 Blood Platelets, 107, 142 Blood pressure, 24, 43, 45, 54, 59, 68, 74, 107, 109, 124, 131, 132, 142, 143 Blood vessel, 59, 104, 107, 108, 109, 110, 112, 117, 126, 135, 143, 144, 145, 147 Body Composition, 6, 9, 25, 107 Body Fluids, 106, 107, 108, 143, 147 Body Mass Index, 7, 19, 107, 134 Bone Density, 6, 9, 107 Bone Marrow, 6, 22, 101, 106, 107, 129, 131, 138, 144 Bowel, 17, 57, 66, 103, 107, 114, 125, 126, 133, 144, 147 Bowel Movement, 107, 114, 144 Brachial, 60, 107 Brachial Artery, 60, 107 Bradykinin, 60, 108, 126, 132, 136 Branch, 97, 108, 134, 135, 143, 145 Bronchi, 108, 117 Bronchial, 64, 67, 108, 123 Bronchitis, 108, 110
Bypass, 13, 108 C Calcium, 108, 111, 129, 132, 142 Capillary, 108, 128, 148 Capillary Permeability, 108 Capsules, 108, 120 Carbohydrate, 8, 108, 121 Carcinogen, 20, 108, 118 Carcinogenesis, 7, 21, 108, 110 Carcinogenic, 106, 108, 125, 138, 144 Carcinoma, 22, 108, 113 Cardiac, 11, 12, 17, 41, 108, 113, 117, 131, 132, 144 Cardiac Output, 17, 108, 144 Cardiovascular, 6, 7, 8, 12, 13, 17, 28, 33, 47, 75, 108, 118, 128, 142 Cardiovascular disease, 6, 8, 13, 33, 47, 108, 128 Carnitine, 16, 109 Case report, 36, 38, 40, 109, 110 Case series, 109, 110 Caspases, 21, 109 Catecholamine, 109, 115 Catheter, 60, 109 Causal, 17, 109, 126 Celecoxib, 16, 22, 109 Cell Cycle, 49, 109, 139 Cell Death, 21, 104, 109, 131 Cell Division, 106, 109, 130, 136 Cell proliferation, 20, 105, 109, 142 Cell Respiration, 102, 109, 134, 140 Central Nervous System, 14, 101, 106, 109, 120, 121, 142 Cerebral, 14, 109, 112, 117 Cerebrospinal, 14, 109, 128, 143 Cerebrospinal fluid, 14, 109, 128, 143 Cerebrovascular, 109 Cerebrum, 109 Chemoprevention, 7, 21, 110 Chemopreventive, 7, 20, 22, 110 Chemotactic Factors, 110, 111 Chemotherapy, 18, 110 Chin, 110, 130 Cholesterol, 13, 59, 60, 61, 106, 110, 113, 115, 123, 124, 128, 144 Cholesterol Esters, 110, 128 Chromatin, 105, 110, 129, 132 Chronic, 14, 21, 23, 64, 66, 67, 110, 117, 118, 122, 125, 127, 136, 144, 147 Chronic Obstructive Pulmonary Disease, 64, 67, 110 Chronic renal, 110, 136
153
Chylomicrons, 110, 128 Cirrhosis, 11, 110 CIS, 16, 110 Clamp, 9, 19, 26, 66, 110 Claudication, 13, 110 Clinical study, 10, 110, 112 Clinical trial, 4, 5, 10, 18, 20, 35, 57, 61, 85, 110, 112, 115, 131, 139, 140 Clomiphene, 31, 33, 110 Cloning, 107, 111 Clot Retraction, 111, 136 Cod Liver Oil, 111, 116 Cognition, 15, 111 Colitis, 23, 57, 90, 111, 126 Collagen, 16, 103, 111, 119, 120, 129, 136, 138 Colloidal, 64, 102, 111, 116, 135 Colon, 19, 20, 23, 111, 125, 126, 127, 142, 147 Combination Therapy, 4, 33, 72, 111 Complement, 37, 103, 111, 136 Complement Activation, 37, 103, 111 Complete remission, 112, 140 Computational Biology, 85, 112 Concomitant, 8, 11, 112 Conjugated, 112, 113 Conjugation, 107, 112 Connective Tissue, 107, 111, 112, 119, 120, 141 Constipation, 68, 112, 126, 142 Constrict, 59, 112 Constriction, 59, 112, 126 Consumption, 16, 112, 133, 134 Continuous infusion, 66, 112 Contraindications, ii, 112 Control group, 15, 112, 137 Controlled clinical trial, 46, 112 Controlled study, 44, 45, 57, 112 Convulsions, 112, 116 Coordination, 6, 112 Coronary, 11, 30, 33, 49, 58, 108, 113, 130, 131, 132 Coronary Disease, 11, 113 Coronary heart disease, 108, 113 Coronary Thrombosis, 113, 130, 131 Coronary Vessels, 113 Corpus, 113, 138, 141 Corpus Luteum, 113, 138 Cortex, 113, 117 Corticosteroids, 23, 113 Cortisol, 5, 102, 113 Curative, 113, 145
Cyclic, 113, 121, 132 Cyproterone, 113, 120 Cysteine, 109, 113, 116 Cysteine Endopeptidases, 109, 113, 116 Cytochrome, 31, 37, 52, 113 Cytokine, 13, 14, 22, 23, 114 Cytoplasm, 105, 114, 129, 131, 132 D Databases, Bibliographic, 85, 114 De novo, 9, 114 Degenerative, 114, 122 Deletion, 105, 114 Delivery of Health Care, 114, 122 Density, 6, 9, 106, 107, 114, 115, 128, 133, 143 Dentate Gyrus, 114, 123 Diabetes Mellitus, 6, 12, 14, 29, 31, 33, 34, 35, 41, 42, 43, 44, 46, 47, 48, 52, 54, 65, 69, 90, 91, 114, 121, 122, 133 Diagnostic procedure, 63, 77, 114 Diastolic, 114, 124 Dietary Fats, 114, 128 Digestion, 106, 107, 114, 126, 128, 135, 144 Digestive system, 62, 114 Dihydrotestosterone, 40, 114, 140 Dilatation, 103, 114, 138, 147 Dilatation, Pathologic, 114, 147 Dilate, 59, 114 Dilation, 108, 114, 147 Dilator, 114, 132 Dimerization, 16, 114 Direct, iii, 6, 12, 16, 20, 64, 79, 115, 119, 140 Disinfectant, 115, 118 Disposition, 29, 115 Dissociation, 102, 115 Distal, 115, 139 Diuresis, 24, 115 Dopamine, 74, 115, 131 Dose-dependent, 42, 115 Double-blind, 17, 23, 35, 39, 44, 57, 115 Drug Interactions, 80, 115 Drug Tolerance, 115, 146 Dyes, 103, 106, 115, 132 Dyslipidemia, 14, 115 Dysuria, 68, 115 E Echocardiography, 58, 115 Eclampsia, 16, 116 Edema, 38, 40, 58, 116, 133, 137 Effector, 21, 101, 111, 116, 132 Efficacy, 19, 21, 22, 23, 28, 35, 54, 57, 60, 116
154 Rosiglitazone
Elastin, 111, 116, 119 Electrocardiogram, 58, 116 Electrolyte, 116, 137, 143 Electrons, 106, 116, 126, 134, 140 Electrophoresis, 23, 116 Embryo, 116, 125, 133 Emphysema, 110, 116 Emulsion, 64, 116 Endocrine System, 116, 132 Endocrinology, 9, 10, 31, 32, 37, 41, 45, 52, 54, 116 Endogenous, 25, 66, 115, 116, 132, 146 Endometrial, 7, 116 Endometrium, 7, 116, 130 Endopeptidases, 113, 116, 138 Endothelial cell, 42, 49, 54, 117 Endothelium, 13, 117, 132, 136 Endothelium, Lymphatic, 117 Endothelium, Vascular, 117 Endothelium-derived, 117, 132 Endotoxemia, 14, 117 Endotoxic, 117, 128 Endotoxin, 14, 117 End-stage renal, 39, 110, 117, 136 Energy balance, 15, 117, 127 Enhancer, 15, 117, 140 Entorhinal Cortex, 117, 123 Environmental Health, 84, 86, 117 Enzymatic, 103, 108, 111, 117, 119, 123 Enzyme, 4, 18, 26, 66, 102, 103, 116, 117, 121, 125, 128, 130, 131, 133, 136, 138, 139, 140, 142, 145, 148 Epidermal, 117, 127 Epidermis, 117, 127, 137 Epigastric, 117, 134 Epinephrine, 102, 115, 117, 132, 147 Epithelial, 17, 20, 22, 23, 24, 117, 118, 122 Epithelial Cells, 17, 20, 22, 23, 24, 118, 122 Epithelium, 20, 117, 118 Erythrocytes, 107, 118 Erythromycin, 18, 118 Erythropoiesis, 64, 67, 118 Escalation, 18, 118 Esophagitis, 118, 145 Esophagus, 114, 118, 140, 144 Estradiol, 8, 118 Estrogen, 7, 110, 113, 118 Estrogen receptor, 110, 118 Estrone, 7, 118 Ethanol, 64, 118 Eukaryotic Cells, 118, 125, 133 Evacuation, 112, 118
Exercise Test, 58, 118 Exercise Therapy, 72, 118 Exocrine, 118, 134 Exogenous, 24, 107, 116, 118, 147 Extracellular, 103, 105, 112, 118, 119, 129, 130, 143 Extracellular Matrix, 112, 119, 129 Extracellular Matrix Proteins, 119, 129 Extracellular Space, 119, 130 Extrapyramidal, 115, 119 Extremity, 13, 119 F Family Planning, 85, 119 Fatigue, 11, 119, 122 Fatty acids, 45, 102, 119, 138, 145 Fatty Liver, 11, 119 Feces, 112, 119, 144 Fibrin, 111, 119, 136, 145 Fibrinogen, 49, 119, 136, 145 Fibrinolytic, 22, 119 Fibrosis, 11, 64, 67, 119 Fistula, 119, 133 Flavoxate, 68, 119 Fluorescence, 15, 120 Flutamide, 8, 120 Forearm, 60, 107, 120 G Gallbladder, 101, 114, 120 Ganglia, 101, 120, 132 Gas, 120, 123, 126, 132 Gastric, 109, 120, 123, 135, 140 Gastrin, 120, 123 Gastritis, 120, 145 Gastrointestinal, 108, 117, 118, 120, 140, 142, 143, 145, 147 Gastrointestinal tract, 118, 120, 142, 143, 147 Gelatin, 23, 120, 121, 145 Gene, 7, 16, 19, 20, 23, 40, 41, 107, 120, 124, 140 Gene Expression, 7, 16, 20, 23, 40, 120 Genetic Markers, 22, 120 Genetics, 10, 53, 112, 120, 135 Genomics, 10, 54, 120 Genotype, 18, 120, 135 Germ Cells, 120, 134, 145 Gestation, 120, 136, 137 Gland, 22, 101, 120, 121, 123, 134, 138, 141, 145 Glucose, 4, 6, 7, 8, 11, 12, 13, 14, 16, 19, 25, 52, 53, 58, 65, 66, 71, 74, 76 Glucose Clamp Technique, 66, 120
155
Glucose Intolerance, 58, 114, 121 Glucose tolerance, 6, 7, 8, 12, 14, 25, 29, 31, 53, 59, 66, 121 Glucose Tolerance Test, 7, 66, 121 Glyburide, 28, 35, 66, 121 Glycine, 103, 121, 142 Glycoprotein, 119, 121 Gonadal, 121, 144 Gonadorelin, 121, 127 Gonadotropin, 8, 121, 127 Gonads, 121, 124 Governing Board, 121, 137 Graft, 13, 121 Gram-negative, 117, 121 Growth, 7, 9, 16, 20, 21, 24, 25 Guanylate Cyclase, 121, 132 H Haptens, 102, 121 Headache, 121, 142 Health Care Costs, 11, 122 Health Expenditures, 122 Health Status, 59, 122 Heart attack, 109, 122 Heart failure, 27, 40, 41, 58, 60, 122, 133 Heme, 106, 113, 122 Hemodynamics, 17, 122 Hemoglobin, 4, 19, 118, 122 Hemorrhage, 121, 122, 144 Hemostasis, 122, 142 Hepatic, 4, 8, 34, 35, 36, 38, 41, 42, 48, 52, 102, 121, 122 Hepatitis, 30, 35, 47, 122 Hepatitis C, 47, 122 Hepatocellular, 11, 36, 122 Hepatocytes, 32, 122 Hepatoma, 49, 122 Hepatotoxic, 4, 122 Hepatotoxicity, 26, 32, 74, 76, 122 Heredity, 120, 122 Heterogeneity, 10, 102, 123 Hippocampus, 14, 114, 123, 144 Hirsutism, 113, 123 Histamine, 103, 123, 140 Homeostasis, 8, 123 Hormonal, 25, 64, 105, 123 Hormonal therapy, 64, 123 Hormone, 7, 8, 9, 23, 25, 58, 67 Hormone therapy, 123 Hydrogen, 101, 106, 108, 119, 123, 131, 134, 135 Hydrolysis, 105, 107, 123, 128, 137, 139 Hydrophobic, 123, 128
Hydroxylysine, 111, 123 Hydroxyproline, 103, 111, 123 Hyperandrogenism, 31, 123 Hypercholesterolemia, 115, 123 Hyperglycaemia, 54, 123 Hyperglycemia, 29, 65, 66, 71, 123 Hyperlipidemia, 22, 25, 60, 61, 68, 115, 124 Hyperlipoproteinemia, 124, 128 Hyperphagia, 52, 124 Hyperplasia, 7, 124 Hypersecretion, 8, 124 Hypertension, 12, 24, 29, 45, 59, 109, 121, 124, 133, 137 Hypertriglyceridemia, 53, 60, 115, 124 Hypertrophy, 12, 124 Hypoglycemic, 10, 71, 124 Hypoglycemic Agents, 71, 124 Hypogonadism, 5, 124 Hypolipidemic, 66, 124 Hypothalamic, 14, 124 Hypothalamus, 121, 124, 143 I Ibuprofen, 20, 124 Id, 55, 90, 91, 96, 98, 124 Ileum, 124, 148 Imidazole, 123, 124, 140 Immune system, 124, 129, 147, 148 Immunity, 13, 124 Immunogenic, 124, 128 Immunohistochemistry, 23, 124 Immunology, 101, 102, 124 Impairment, 14, 34, 45, 54, 124, 130 In situ, 16, 124 In Situ Hybridization, 16, 125 In vitro, 19, 22, 24, 26, 31, 32, 37, 46, 52, 66, 125 In vivo, 14, 20, 46, 66, 125, 130 Incontinence, 68, 125, 133 Indicative, 125, 134, 147 Indinavir, 11, 125 Indomethacin, 20, 125 Induction, 11, 21, 103, 125 Infantile, 125, 128 Infarction, 113, 125, 130, 131 Infection, 9, 11, 23, 25, 106, 110, 125, 129, 144, 148 Infertility, 24, 125 Inflammation, 11, 13, 14, 17, 23 Inflammatory bowel disease, 17, 66, 125 Infusion, 66, 120, 125, 146 Ingestion, 121, 124, 125 Inhalation, 64, 67, 102, 125
156 Rosiglitazone
Initiation, 22, 125, 138, 146 Inlay, 125, 140 Inositol, 37, 125 Inotropic, 115, 126 Insight, 10, 126 Insomnia, 126, 142 Insulin-dependent diabetes mellitus, 126 Intermittent, 13, 126 Intermittent Claudication, 13, 126 Internal Medicine, 9, 11, 12, 36, 38, 42, 46, 116, 126 Intervention Studies, 26, 126 Intestinal, 17, 121, 126 Intestine, 66, 107, 126, 127 Intracellular, 109, 125, 126, 132, 137, 140, 142 Intravenous, 125, 126 Intrinsic, 102, 126 Invasive, 124, 126, 129 Ions, 106, 115, 116, 123, 126 Irritable Bowel Syndrome, 126, 133 Ischemia, 13, 105, 126 Islet, 45, 53, 126 K Kallidin, 108, 126 Kb, 84, 126 Keratin, 127 Keratinocytes, 44, 127 Kidney Failure, 117, 127 L Labile, 111, 127 Large Intestine, 114, 126, 127, 140, 143 Latent, 127, 137 Leptin, 14, 32, 52, 127 Leukemia, 21, 127 Leukocytes, 107, 110, 125, 127, 131, 132 Leuprolide, 8, 127 Libido, 103, 127 Library Services, 96, 127 Life cycle, 107, 127 Life Expectancy, 11, 127 Ligament, 127, 138 Ligands, 15, 17, 19, 20, 21, 22, 23, 127 Ligation, 21, 127 Linkage, 120, 127 Lipase, 22, 67, 128, 133 Lipid, 3, 8, 11, 12, 26, 31, 34, 41, 46, 61, 69, 104, 105, 108, 121, 126, 128, 133, 146 Lipid A, 9, 41, 128, 133 Lipodystrophy, 5, 6, 22, 37, 41, 44, 58, 61, 74, 128 Lipolysis, 5, 9, 19, 37, 48, 68, 128
Lipophilic, 23, 128 Lipopolysaccharides, 128 Lipoprotein, 9, 19, 22, 48, 115, 121, 128 Lipoprotein Lipase, 22, 128 Lipoprotein(a), 48, 128 Liposarcoma, 28, 59, 128 Liver, 4, 9, 11, 18, 25, 26, 66, 75 Localization, 124, 128 Localized, 12, 123, 125, 128, 133, 136, 147 Low-density lipoprotein, 115, 128 Lumbar, 15, 128, 143 Lumbar puncture, 15, 128, 144 Lymph, 106, 117, 129 Lymphatic, 117, 125, 129, 133 Lymphocytes, 66, 104, 127, 129, 148 Lymphoid, 21, 104, 113, 129 M Macrophage, 13, 14, 129 Magnetic Resonance Imaging, 12, 13, 58, 129 Malignancy, 21, 129 Malignant, 21, 129, 131, 141 Malnutrition, 102, 105, 129 Mammary, 21, 128, 129 Matrix metalloproteinase, 44, 129 Medial, 14, 105, 129 Mediate, 14, 115, 129, 140 Mediator, 129, 142 Medical Records, 34, 129 Medicament, 64, 129, 145 MEDLINE, 85, 129 Membrane, 21, 66, 105, 111, 118, 119, 121, 129, 130, 131, 133, 135, 141, 142, 146 Memory, 14, 129 Meninges, 109, 129 Menopause, 130, 137 Menstrual Cycle, 24, 130, 138 Menstruation, 103, 130, 133 Mental, iv, 4, 62, 84, 86, 110, 111, 115, 119, 129, 130, 139 Mental Disorders, 62, 130 Metabolic disorder, 9, 25, 65, 130 Metabolite, 107, 118, 130, 137 Metastasis, 129, 130 MI, 19, 28, 33, 34, 35, 38, 39, 42, 43, 45, 48, 99, 130 Microbe, 130, 146 Microdialysis, 19, 130 Microorganism, 130, 148 Microscopy, 15, 130 Microtubules, 130, 134 Midaxillary line, 130, 148
157
Milliliter, 107, 130 Millimeter, 130, 148 Mineralization, 8, 130 Mitosis, 105, 130 Mobility, 22, 130 Modification, 16, 26, 72, 103, 130, 139 Modulator, 20, 131 Molecular, 7, 13, 21, 22, 24, 53, 85, 87, 107, 112, 114, 119, 126, 131, 136, 140, 141 Molecule, 4, 104, 106, 108, 111, 115, 116, 117, 123, 131, 134, 140, 142 Monitor, 23, 131, 133 Monoamine, 67, 131 Monocytes, 14, 40, 127, 131 Mononuclear, 131 Monotherapy, 4, 29, 34, 44, 45, 72, 73, 131 Motility, 44, 125, 131, 142 Mucosa, 131, 145 Mucus, 131, 147 Multicenter study, 28, 131 Myocardial Ischemia, 113, 131 Myocardium, 130, 131 N Natriuresis, 24, 131 NCI, 1, 59, 61, 83, 110, 131 Necrosis, 104, 125, 130, 131 Need, 3, 8, 23, 69, 71, 92, 102, 110, 129, 131, 146 Neonatal, 16, 131 Neoplasm, 131, 141 Nephropathy, 53, 131 Nerve, 102, 110, 129, 132, 146 Nervous System, 14, 102, 109, 129, 132, 143, 145 Neuroendocrine, 5, 15, 132 Neuromuscular, 101, 132 Neuromuscular Junction, 101, 132 Neurotransmitters, 132, 142 Neutropenia, 18, 132 Neutrophils, 127, 132 Nifedipine, 43, 132 Nitric Oxide, 46, 132 Nitrogen, 103, 119, 132, 146 Nitroglycerin, 60, 132 Nitroprusside, 60, 132 Norepinephrine, 102, 115, 132, 142 Nuclear, 12, 17, 19, 20, 21, 22, 23, 112, 116, 118, 131, 133 Nuclei, 112, 116, 129, 130, 133 Nucleic acid, 125, 132, 133, 139 Nucleus, 105, 110, 113, 114, 118, 129, 131, 132, 133
Nutritional Status, 5, 133 O Octreotide, 25, 133 Oedema, 42, 133, 137 Oligomenorrhea, 133, 137 Opacity, 114, 133 Organelles, 114, 131, 133 Orlistat, 68, 133 Orthostatic, 133 Osmotic, 102, 133 Ossification, 133 Osteogenesis, 6, 133 Osteoporosis, 10, 133 Ovaries, 123, 134, 137, 142 Ovary, 24, 74, 113, 118, 121, 134 Overweight, 13, 55, 134 Ovulation, 24, 33, 37, 74, 104, 110, 134 Ovum, 113, 120, 127, 134, 138 Oxidation, 19, 37, 101, 107, 113, 134, 145 Oxidation-Reduction, 107, 134 Oxidative metabolism, 18, 102, 134 Oxygen Consumption, 118, 134, 140 P Paclitaxel, 18, 134 Palliative, 113, 134, 145 Pancreas, 65, 101, 106, 114, 126, 128, 134, 143, 147 Pancreatic, 53, 109, 134 Partial remission, 134, 140 Particle, 64, 67, 134, 143 Pathogenesis, 9, 10, 11, 134 Pathologic, 105, 106, 113, 134 Pathologic Processes, 105, 134 Pathophysiology, 14, 17, 134 Pelvic, 134, 138 Peptic, 135, 145 Peptide, 103, 116, 127, 135, 137, 138, 139 Perfusion, 120, 135 Peritoneal, 105, 133, 135 Peritoneal Cavity, 105, 133, 135 Petrolatum, 116, 135 PH, 107, 135 Pharmaceutical Preparations, 118, 120, 135 Pharmacogenetics, 18, 135 Pharmacokinetic, 18, 36, 135 Pharmacologic, 18, 72, 105, 135, 146 Phenolphthalein, 116, 135 Phenotype, 18, 20, 135 Phospholipids, 119, 126, 128, 135 Phosphorus, 108, 135 Phosphorylated, 23, 135
158 Rosiglitazone
Phosphorylation, 15, 17, 46, 135 Physical Examination, 58, 59, 135 Physical Fitness, 118, 135 Physiologic, 5, 8, 102, 107, 130, 135, 140, 142 Physiology, 8, 45, 116, 136 Pilot study, 23, 36, 38, 136 Placenta, 118, 136, 138 Plants, 105, 120, 132, 136, 141, 146 Plasma, 3, 12, 13, 14, 24, 65 Plasma protein, 102, 117, 136 Plasmin, 22, 136 Plasminogen, 136 Plasminogen Activators, 136 Platelet Aggregation, 103, 132, 136 Platelets, 132, 136 Plethysmography, 60, 136 Pleural, 133, 136 Pleural cavity, 133, 136 Pneumonia, 64, 67, 112, 136 Polycystic, 24, 31, 33, 37, 74, 123, 136, 137 Polycystic Ovary Syndrome, 31, 33, 37, 74, 123, 137 Polypeptide, 103, 111, 119, 136, 137, 143 Posterior, 103, 130, 134, 137 Postmenopausal, 19, 133, 137 Postnatal, 137, 144 Postprandial, 6, 72, 137 Potassium, 10, 137 Potentiation, 24, 137, 142 Practice Guidelines, 86, 90, 91, 137 Pravastatin, 68, 137 Precancerous, 110, 137 Preclinical, 22, 137 Precursor, 115, 116, 117, 132, 136, 137, 146, 147 Predisposition, 69, 137 Pre-Eclampsia, 17, 137 Pre-eclamptic, 116, 137 Prevalence, 7, 11, 13, 17, 66, 137 Prickle, 127, 137 Primary endpoint, 12, 137 Probe, 18, 130, 138 Progesterone, 25, 138, 144 Progression, 13, 28, 104, 138 Progressive, 65, 110, 115, 118, 121, 131, 138 Progressive disease, 65, 138 Proline, 111, 123, 138 Promoter, 39, 53, 138 Promotor, 138, 140 Promyelocytic leukemia, 21, 138 Proportional, 60, 138
Prospective study, 12, 138 Prostaglandins, 125, 138 Prostaglandins A, 125, 138 Prostate, 20, 106, 138, 147 Protease, 9, 11, 22, 61, 111, 125, 138 Protease Inhibitors, 9, 11, 22, 61, 138 Protein C, 102, 104, 127, 128, 138 Protein S, 107, 118, 139 Proteins, 15, 20 Proteinuria, 54, 137, 139 Proteolytic, 23, 66, 111, 119, 136, 139 Protocol, 13, 139 Proto-Oncogene Proteins, 134, 139 Proto-Oncogene Proteins c-mos, 134, 139 Proximal, 14, 24, 115, 139, 141 Psychic, 127, 130, 139 Public Policy, 85, 139 Publishing, 27, 139 Pulmonary, 40, 42, 58, 64, 67, 107, 112, 118, 127, 139, 147 Pulmonary Artery, 107, 139, 148 Pulmonary Edema, 58, 127, 139 Pulse, 68, 131, 139 Purines, 139, 142 Q Quality of Life, 13, 22, 23, 26, 139 R Race, 25, 139 Radiation, 120, 139, 140, 149 Radioactive, 123, 133, 140 Randomized, 3, 4, 12, 15, 17, 23, 28, 33, 35, 44, 45, 52, 57, 116, 140 Ranitidine, 48, 140 Reabsorption, 24, 140 Receptor, 8, 10, 15, 17, 19, 20, 21, 23, 24, 53, 61, 68, 74 Receptors, Serotonin, 140, 142 Recombinant, 6, 41, 140 Recombination, 112, 120, 140 Rectum, 104, 107, 111, 114, 120, 125, 127, 138, 140, 145 Recurrence, 110, 140 Reductase, 4, 68, 137, 140 Refer, 1, 111, 128, 140, 141 Reflux, 140, 145 Refractory, 23, 140 Regimen, 34, 116, 140 Remission, 23, 140 Respirable, 64, 67, 140 Respiration, 131, 140 Response Elements, 17, 140 Restoration, 6, 24, 140, 148
159
Retinoid, 7, 141 Retrospective, 34, 141 Rheumatism, 124, 141 Risk factor, 11, 12, 13, 138, 141 Rod, 110, 117, 141 Rubber, 60, 101, 141 S Salivary, 114, 141 Salivary glands, 114, 141 Saponins, 141, 144 Sarcoma, 59, 141, 143 Screening, 58, 110, 141, 147 Second cancer, 20, 141 Secretion, 14, 25, 32, 40, 44, 45, 65, 121, 123, 124, 126, 131, 133, 140, 141 Secretory, 53, 141 Sedentary, 69, 141 Sediment, 141, 147 Semen, 138, 141 Senile, 134, 141 Septal, 141 Septum, 12, 141 Septum Pellucidum, 141 Serine, 46, 66, 116, 139, 142 Serotonin, 67, 140, 142, 146 Serous, 117, 142 Serum, 4, 8, 25, 30, 48, 52, 61, 102, 103, 111, 121, 128, 142 Sex Characteristics, 103, 142, 145 Shivering, 142, 145 Shock, 117, 142 Sibutramine, 68, 142 Side effect, 22, 47, 58, 68, 69, 79, 102, 142, 146 Sigmoid, 142 Sigmoidoscopy, 57, 142 Signal Transduction, 126, 142 Signs and Symptoms, 140, 142 Skeletal, 13, 42, 48, 53, 103, 110, 143 Skeleton, 143 Skull, 143, 145 Small intestine, 110, 123, 124, 126, 143 Smooth muscle, 68, 103, 105, 119, 123, 132, 143, 145 Social Environment, 139, 143 Sodium, 24, 60, 131, 140, 143 Soft tissue, 59, 107, 143 Soft tissue sarcoma, 59, 143 Solvent, 64, 106, 118, 133, 143 Somatostatin, 133, 143 Sound wave, 60, 143, 147 Specialist, 92, 114, 143
Species, 26, 117, 120, 130, 139, 143, 144, 146, 148, 149 Specificity, 102, 116, 143 Sperm, 103, 143 Spinal cord, 105, 107, 109, 110, 129, 132, 143 Spinal tap, 128, 143 Spinous, 117, 127, 144 Stabilization, 20, 144 Stabilizer, 64, 144 Standard therapy, 23, 144 Steatosis, 12, 38, 119, 144 Steel, 110, 144 Stem Cells, 21, 144 Sterility, 33, 37, 125, 144 Steroid, 6, 8, 23, 113, 141, 144 Stimulants, 69, 144 Stomach, 101, 114, 118, 120, 121, 123, 135, 140, 143, 144 Stool, 111, 125, 126, 127, 144 Stress, 14, 109, 113, 126, 137, 141, 144 Stroke, 62, 84, 108, 109, 144 Stroke Volume, 108, 144 Stromal, 22, 144 Styrene, 141, 144 Subacute, 125, 144 Subclinical, 125, 144 Subcutaneous, 6, 8, 25, 32, 44, 101, 116, 128, 133, 144, 148 Subiculum, 123, 144 Subspecies, 143, 144 Substance P, 118, 130, 141, 144 Substrate, 22, 145 Sucralfate, 38, 53, 145 Suppositories, 120, 145 Suppression, 9, 22, 25, 40, 145 Sympathomimetic, 115, 117, 132, 145 Symphysis, 110, 138, 145 Symptomatic, 13, 145 Systemic, 13, 48, 54, 64, 67, 80, 107, 117, 122, 125, 133, 145 Systolic, 12, 124, 145 T Temporal, 14, 123, 145 Testis, 118, 121, 145 Testosterone, 5, 8, 25, 40, 140, 145 Therapeutics, 28, 29, 30, 33, 34, 36, 38, 44, 48, 80, 145 Thermogenesis, 68, 145 Thorax, 101, 128, 145 Threonine, 139, 142, 145 Threshold, 124, 145
160 Rosiglitazone
Thrombin, 119, 136, 138, 145 Thrombosis, 30, 41, 139, 144, 145 Thyroxine, 102, 145 Tissue, 7, 8, 14, 19, 23, 25, 59, 60, 68, 73, 101, 104, 105, 106, 107, 108, 110, 112, 115, 116, 117, 119, 121, 124, 126, 127, 129, 131, 132, 133, 135, 136, 140, 142, 143, 145, 146, 148 Tolerance, 6, 7, 9, 12, 14, 25, 53, 59, 66, 101, 121, 146 Tomography, 13, 15, 107, 146 Topical, 118, 135, 146 Toxic, iv, 18, 26, 69, 106, 112, 122, 124, 144, 146 Toxicity, 4, 16, 18, 23, 25, 46, 115, 145, 146 Toxicology, 26, 49, 86, 146 Toxins, 104, 125, 146 Traction, 110, 146 Transcription Factors, 19, 21, 22, 23, 140, 146 Transfection, 22, 107, 146 Transfusion, 122, 146 Translation, 103, 118, 146 Translational, 10, 146 Translocation, 118, 146 Transmitter, 101, 105, 115, 129, 132, 146 Trees, 141, 146 Triglyceride, 48, 124, 146 Troglitazone, 3, 4, 20, 22, 25, 26, 28, 31, 32, 35, 37, 40, 47, 49, 52, 54, 65, 66, 146 Tryptophan, 111, 142, 146 Tuberculosis, 112, 146 Tumor marker, 106, 146 Type 2 diabetes, 4, 6, 10, 11, 12, 13, 14, 19, 52, 53, 54, 71, 74, 75, 76, 90, 91 Tyrosine, 115, 147 U Ulcer, 145, 147 Ulcerative colitis, 23, 30, 57, 125, 147 Ultrasonography, 13, 147 Ultrasound test, 58, 147 Unconscious, 124, 147 Urethra, 138, 147
Urinalysis, 58, 147 Urinary, 45, 106, 119, 125, 147 Urine, 16, 58, 59, 68, 106, 107, 115, 118, 125, 131, 139, 147 Uterus, 113, 116, 130, 134, 138, 147 V Vaccine, 101, 139, 147 Vascular, 11, 13, 30, 41, 53, 65, 117, 125, 132, 133, 136, 147 Vasoactive, 32, 147 Vasodilation, 13, 147 Vasodilator, 108, 115, 123, 132, 147 Vein, 13, 103, 126, 133, 147 Venous, 132, 133, 139, 147 Ventricle, 123, 124, 139, 145, 147, 148 Ventricular, 12, 148 Ventricular Dysfunction, 12, 148 Venules, 107, 108, 117, 148 Veterinary Medicine, 53, 85, 148 Vinca Alkaloids, 148 Vinorelbine, 18, 148 Viral, 9, 148 Virilism, 123, 148 Virulence, 146, 148 Virus, 117, 122, 148 Visceral, 6, 8, 13, 25, 34, 148 Visceral fat, 6, 9, 34, 148 Vitamin A, 126, 141, 148 Vitro, 19, 22, 24, 26, 52, 66, 148 Vivo, 14, 20, 66, 148 W Waist circumference, 6, 148 Weight Gain, 69, 148 Weight Lifting, 60, 148 White blood cell, 104, 127, 129, 131, 132, 148 Wound Healing, 129, 148 X Xenograft, 104, 149 X-ray, 58, 107, 120, 133, 144, 149 Y Yeasts, 135, 149
