Pravastatin - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

PRAVASTATIN A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES J AMES N...

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PRAVASTATIN A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES

J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 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., 1960Pravastatin: 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: 0-597-84556-5 1. Pravastatin-Popular works. I. Title.

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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.

Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail: [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.

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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on pravastatin. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.

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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.

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About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes&Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health

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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON PRAVASTATIN ........................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Pravastatin.................................................................................... 4 E-Journals: PubMed Central ....................................................................................................... 11 The National Library of Medicine: PubMed ................................................................................ 12 CHAPTER 2. NUTRITION AND PRAVASTATIN ................................................................................. 61 Overview...................................................................................................................................... 61 Finding Nutrition Studies on Pravastatin .................................................................................. 61 Federal Resources on Nutrition ................................................................................................... 65 Additional Web Resources ........................................................................................................... 65 CHAPTER 3. CLINICAL TRIALS AND PRAVASTATIN........................................................................ 69 Overview...................................................................................................................................... 69 Recent Trials on Pravastatin ....................................................................................................... 69 Keeping Current on Clinical Trials ............................................................................................. 70 CHAPTER 4. PATENTS ON PRAVASTATIN ........................................................................................ 73 Overview...................................................................................................................................... 73 Patents on Pravastatin................................................................................................................. 73 Patent Applications on Pravastatin............................................................................................. 85 Keeping Current ........................................................................................................................ 103 CHAPTER 5. BOOKS ON PRAVASTATIN ......................................................................................... 105 Overview.................................................................................................................................... 105 Book Summaries: Online Booksellers......................................................................................... 105 Chapters on Pravastatin ............................................................................................................ 105 CHAPTER 6. PERIODICALS AND NEWS ON PRAVASTATIN............................................................ 107 Overview.................................................................................................................................... 107 News Services and Press Releases.............................................................................................. 107 Academic Periodicals covering Pravastatin ............................................................................... 111 CHAPTER 7. RESEARCHING MEDICATIONS .................................................................................. 113 Overview.................................................................................................................................... 113 U.S. Pharmacopeia..................................................................................................................... 113 Commercial Databases ............................................................................................................... 114 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 117 Overview.................................................................................................................................... 117 NIH Guidelines.......................................................................................................................... 117 NIH Databases........................................................................................................................... 119 Other Commercial Databases..................................................................................................... 121 APPENDIX B. PATIENT RESOURCES ............................................................................................... 123 Overview.................................................................................................................................... 123 Patient Guideline Sources.......................................................................................................... 123 Finding Associations.................................................................................................................. 125 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 127 Overview.................................................................................................................................... 127 Preparation................................................................................................................................. 127 Finding a Local Medical Library................................................................................................ 127 Medical Libraries in the U.S. and Canada ................................................................................. 127 ONLINE GLOSSARIES................................................................................................................ 133 Online Dictionary Directories ................................................................................................... 133

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PRAVASTATIN DICTIONARY ................................................................................................. 135 INDEX .............................................................................................................................................. 187

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FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with pravastatin 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 pravastatin, 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 pravastatin, 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 pravastatin. 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 pravastatin, 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 pravastatin. The Editors

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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.

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CHAPTER 1. STUDIES ON PRAVASTATIN Overview In this chapter, we will show you how to locate peer-reviewed references and studies on pravastatin.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and pravastatin, 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 “pravastatin” (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: •

Pravastatin for Secondary Prevention of Cardiovascular Events in Persons with Mild Chronic Renal Insufficiency Source: Annals of Internal Medicine. 138(2): 98-104. January 21, 2003. Contact: Available from American College of Physicians. American Society of Internal Medicine. 190 North Independence Mall West, Philadelphia, PA 19106-1572. Website: www.acponline.org. Summary: Cardiovascular disease is a common cause of morbidity and death in persons with renal (kidney) insufficiency. Although statins are effective for secondary prevention of cardiovascular events in the general population, they have not been specifically studied in chronic renal insufficiency (CRI). This article reports on a study undertaken to determine whether pravastatin is effective and safe for secondary

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prevention of cardiovascular events in persons with CRI. The study included 1,711 participants with CRI from the Cholesterol and Recurrent Events (CARE) study, a randomized trial of pravastatin versus placebo. After a median followup of 58.9 months, the incidence of the primary end point (death from coronary disease or symptomatic nonfatal myocardial infarction, MI) was lower in participants receiving pravastatin than in those receiving placebo. Pravastatin was associated with lower adjusted hazard ratios for major coronary events and for coronary revascularization, but not total mortality or stroke. Tests for interaction suggested that the observed benefit was independent of the presence and severity of renal insufficiency. Incidence of side effects was similar in persons receiving pravastatin and those receiving placebo. The authors conclude that pravastatin is effective and appears safe for secondary prevention of cardiovascular events in persons with mild CRI. Since statins may be underused in this setting, physicians should consider prescribing them for patients with CRI and known coronary disease. 1 figure. 3 tables. 22 references. •

Effect of Pravastatin on Loss of Renal Function in People with Moderate Chronic Renal Insufficiency and Cardiovascular Disease Source: Journal of the American Society of Nephrology. 14(6): 1605-1613. June 2003. Summary: Limited data suggest that drugs called statins may slow the loss of renal function in individuals with chronic renal (kidney) insufficiency (CRI). This article reports on a study conducted to determine whether pravastatin reduced rates of loss of kidney function in people with moderate CRI. Among all individuals with the requisite kidney function measures (n = 690), the estimated glomerular filtration rate (GFR, a measure of kidney function) decline in the pravastatin group was not significantly different from that in the placebo group. However, there was a significant inverse relation between GFR before treatment and slowing of renal function loss with pravastatin use, with more benefit in those with lower GFR at baseline. Pravastatin also reduced rates of renal loss to a greater extent in participants with proteinuria (protein in the urine) than without proteinuria at baseline. The authors conclude that pravastatin may slow renal function loss in individuals with moderate to severe kidney disease, especially those with proteinuria. The authors call for confirmation of these findings by a large randomized trial conducted specifically in people with CRI. 3 figures. 3 tables. 40 references.

Federally Funded Research on Pravastatin The U.S. Government supports a variety of research studies relating to pravastatin. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to pravastatin. 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).

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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 pravastatin. The following is typical of the type of information found when searching the CRISP database for pravastatin: •

Project Title: 8MG CERIVASTATIN VS 4MG CERIVASTATIN & PLACEBO & PRAVASTATIN IN HYPER Principal Investigator & Institution: Crouse, John R.; Professor; Wake Forest University 2240 Reynolda Rd Winston-Salem, Nc 27106 Timing: Fiscal Year 2002; Project Start 01-MAR-2002; Project End 28-FEB-2003 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ALLHAT--ANTIHYPERTENSIVE & LIPID LOWERING TREATMENT TO PREVENT HEART ATTACK Principal Investigator & Institution: Lawton, William J.; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002 Summary: The goals of the study are to determine whether the incidence of fatal coronary heart disease and non-fatal myocardial infarction differs between subjects treated with diuretics versus treatment with a calcium antagonist, ACE inhibitor, or alpha blocker. The study will also determine whether lowering serum cholesterol with Pravastatin reduces death from all causes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EFFECT OF PRAVASTATIN AND ATORVASTATIN ON COENZYME Q10 Principal Investigator & Institution: Bleske, Barry E.; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EFFECTS OF SBE ON MALE MONKEYS Principal Investigator & Institution: Adams, Michael R.; Wake Forest University 2240 Reynolda Rd Winston-Salem, Nc 27106 Timing: Fiscal Year 2002 Summary: (Adapted from Applicant's Abstract) There is no means of coronary heart disease prevention for men that combines the qualities of safety, effectiveness, wide acceptability and low cost. While the "statin" group of compounds, e.g., lovastatin, pravastatin, is effective in preventing coronary events, there are issues regarding side effects, compliance and cost that limit their use. Soy phytoestrogens may represent an alternative to pharmacologic means of coronary heart disease prevention. There is limited evidence indicating that soy consumption inhibits atherogenesis and has favorable effects on coronary vascular reactivity while having favorable or neutral effects on other organ systems. The major objective of Project 2 is to assess the usefulness of soy phytoestrogens in primary cardioprotection of adult male monkeys.

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The study will address directly whether long-term soy consumption is without adverse effects on the reproductive system, cognition, social or sexual behavior and function and determine if it has favorable effects on the prostate gland. Ninety cynomolgus monkeys will be randomized to three treatment groups: 1) placebo atherogenic diet (n=30), 2) low phytoestrogen atherogenic diet (58 mg/1800 Cal) (n=30) and 3) high phytoestrogen atherogenic diet (120 mg/1800 Cal) (n=30). Diets are identical in atherogenicity and nutritional content; they differ only in phytoestrogen content. During a 36 month treatment period, assessments will be made of plasma lipoproteins, blood pressure, arterial vasomotor function, sociosexual function, testicular endocrine and spermatogenic function, and cognitive function. Postmortem assessments will be made of atherosclerosis extent and arterial expression of estrogen receptors (alpha and beta). In addition, immunohistochemical and histomorphometric markers of prostatic hyperplasia and neoplasia will be studied as will histomorphometric markers of mammary gland hyperplasia and neoplasia. Spermatogenesis will also be assessed. Finally, assessments will be made of behavior-relevant immunohistochemical markers of estrogenic stimulation in the central nervous system. Since the body of data that exists currently regarding the effects of soy on the cardiovascular, reproductive, and central nervous systems is quite limited, this study represents a necessary step in elucidating the potential for a favorable public health impact of widespread soy consumption by men. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HEPATIC DRUG TRANSPORTERS IN DRUG DISPOSITION Principal Investigator & Institution: Kim, Richard B.; Assistant Professor; Medicine; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2003; Project Start 01-JUL-1998; Project End 30-JUN-2007 Summary: (provided by applicant): Transporters are increasingly recognized as important processes in drug disposition. More recently, functional characterization of drug uptake transporters has revealed that a family of drug uptake transporters known as the Organic Anion Transporting Polypeptides (OATPs), are critical to the cellular uptake of drugs into organs such as the liver, intestine, and brain. Studies have revealed that certain human OATPs such as OATP-C and OATP-8 may be the key hepatic drug uptake transporters, while OATP-A expression at the level of the blood brain barrier may be responsible for the CNS entry of certain drugs. We are now able to show that OATP-A is expressed in the small intestines, and may be a key transporter responsible enhancing the gastrointestinal absorption of various drugs in clinical use. It is our hypothesis that intersubject variability in the expressed level and activity of OATP transporters affects drug disposition and responsiveness. However, the extent of our knowledge regarding human OATP transporters is limited. Studies carried out from this laboratory have identified a number of single nucleotide polymorphisms (SNPs) in OATP transporters importantly associated with drug disposition and response. Accordingly, in this application, studies on the role of genetic variability in certain human OATP transporters to transporter function, both in vitro and in vivo, are outlined. Specific Aim 1 is focused studies on the in vitro functional characterization of allelic variants newly identified by this laboratory in OATP-A, OATP-8 and OATP-C. In Specific Aim 2, to better understand the interplay between OATP-mediated drug uptake versus P-glycoprotein (MDR1) or MRP2 (cMOAT)-mediated drug efflux, studies are proposed on the creation of model cell lines expressing an OATP transporter along with P-glycoprotein or MRP2, in combinations reflective of organs such as the liver, intestine and brain. In Specific Aim 3, the role of commonly occurring SNPs in OATP-C, which

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studies from this laboratory had shown to be functionally significant in vitro, will be tested in human subjects using the well-known OATP-C-specific substrate, pravastatin, and a newly identified substrate, rifampin, as in vivo probes for this transporter. Moreover, variability in the extent of rifampin-mediated induction of the drug metabolizing enzyme, CYP3A, among subjects with variant OATP-C alleles, will also be tested. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMPROVED ACTIONS OF NITRATES AND STATINS WITH LARGININE Principal Investigator & Institution: Caldwell, Ruth B.; Professor; Nitrosystems, Inc. 512 Telfair St Augusta, Ga 30901 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-AUG-2004 Summary: (provided by applicant): This project seeks to develop safer, more effective and enduring: 1) nitrate therapy for angina and congestive heart failure using nitroglycerin (GTN) or isosorbide mononitrate (ISMN) and 2) statin therapy [pravastatin (PRA) or simvastatin (SIM)] for unstable angina and stroke, by their combination with L-arginine (L-arginine). Nitrovasodilators are highly effective acutely, but their usefulness for chronic therapy is limited due to the rapid development of tolerance to their vasodilating effects. NitrOSystems, Inc. has discovered an additional endothelial cell (EC)-dependent mechanism of GTN-induced vasodilation and tolerance and that tolerance can be prevented by treatment with supplemental L-arginine. Data show that GTN activates EC nitric oxide synthase (eNOS) to produce NO from its substrate Larginine. It is known that the intracellular supply of L-arginine can become limiting in diseases characterized by vascular dysfunction, that diminished availability of Larginine as a substrate for eNOS can result in EC damage due to formation of superoxide anion (SOA) and other reactive oxygen species and that treatment with supplemental L-arginine can prevent EC dysfunction. Statins or HMG CoA reductase inhibitors, by mechanisms unrelated to lowering lipids, activate eNQS and inhibit platelet aggregation. Formation of SOA is also increased by statins. It is hypothesized that sustained elevated extracellular levels of L-arginine are required for optimal therapeutic effects of nitrates and the statins and that supplemental L-arginine will potentiate drug actions by reducing formation of SOA. Specific aims are to: 1. Determine the ability of GTN, ISMN, PRA, SIM to activate NOS and produce SOA in EC and the ability of supplemental L-arginine to prevent SOA formation. 2. Determine the ability of supplemental L-arginine to prevent SOA formation and nitrite tolerance in animals. 3. Develop an IV formulation of GTN in combination with L-arginine and an oral combined sustained release formulation of ISMN and L-arginine. 4. Develop an oral combined sustained release formulation of SIM and L-arginine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PHARMACOGENETICS OF THE STATIN RESPONSE Principal Investigator & Institution: Schaefer, Ernst J.; Professor; None; Tufts University Boston Boston, Ma 02111 Timing: Fiscal Year 2003; Project Start 29-SEP-2003; Project End 31-AUG-2007 Summary: (provided by applicant): Coronary heart disease (CHD) is the leading cause of death and disability in our society. Most CHD deaths occur in subjects over 70 years of age. Significant independent CHD risk factors are age, gender, elevated low density lipoprotein (LDL) cholesterol (C), decreased high density lipoprotein (HDL) C,

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hypertension, smoking, diabetes, elevated lipoprotein (a) or Lp(a) (LDL C> 50% reduction), and elevated C-reactive protein. In this response to RFA HL-03-001 (ancillary pharmacogenetic studies), we propose to study 2804 male and 3000 female participants in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER), who were selected for age 70-82 years, having vascular disease coronary, cerebral or peripheral) or increased CHD risk due to smoking, hypertension or diabetes and total cholesterol levels between 4.0 and 9.0 mml/L or 151 and 340 mg/dl. In this randomized controlled trial pravastatin decreased LDL C 34% and triglyceride 12% and raised HDL C 5%. Creactive protein and Lp(a) values have already been measured. Fatal and nonfatal myocardial infarction (MI) were decreased by 19%, and fatal MI 24%, but increased risk of new cancer were noted in the pravastatin group over 3.2 years as compared to the placebo group (all p<0.01) (Lancet 360: 1623-30, 2002). Benefit was greatest in subjects with low HDL C (<1.1 lmml/L or 43 mg/dl). No benefit of pravastatin versus placebo on cognitive function or stroke was noted. We and others have shown that statins increase large alpha 1 migrating apolipoprotein A-I containing HDL, decrease plasma lathosterol, a marker of cholesterol synthesis, and increase plasma betasitosterol, a marker of cholesterol absorption as well as decrease cholesterol ester transfer protein (CETP) mass. We propose to measure HDL subspecies, CETP mass, lathosterol, and beta-sitosterol in the 292 subjects who developed CHD while on pravastatin and in a control group (n=292) who did not develop CHD on pravastatin. We propose to isolate DNA in all subjects, carry out sequencing for single nucleotide polymorphism detection in 5 male and 5 female hyper-responders and the same number of hypo-responders (LDL C <10% reduction) and then genotyping at all SNPs on the two 292 patients groups, and the informative SNP detection on the entire 5804 cohort at the following gene loci: ATP binding cassette transporters G5 and G8 (ABCG5, ABCG8), CETP; HMG CoA reductase, apolipoprotein E, lipoprotein and hepatic lipase, microsomal transfer protein, C-reactive protein, connexin, plasminogen activator type I inhibitor and stromelysin I. These genes have been selected because of our own preliminary studies, and their known key role in cholesterol absorption and lipoprotein metabolism or CHD. We hypothesize that response to pravastatin in terms of lowering of LDL C, triglycerides and C-reactive protein, and HDL C raising will be related to specific genotypes and haplotypes. We also hypothesize that subjects with the greatest LDL Cand C-reactive protein-lowering, the greatest increase in large alpha HDL particles, the greatest reduction in lathosterol and the least increase in beta-sitosterol will have the greatest benefit in CHD risk reduction, and that these changes will be related to specific genotypes and haplotypes of the candidate genes being examined. These results can be used to formulate guidelines for identifying elderly subjects for statin treatment to prevent future CHD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STATIN LACTONES IN STATIN TOXICITY Principal Investigator & Institution: Christians, Uwe; Associate Professor; Anesthesiology; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2003; Project Start 08-APR-2003; Project End 31-MAR-2007 Summary: (provided by applicant): 3-Hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase inhibitors (statins) have emerged as the most valuable cholesterollowering drugs. Statins have wide therapeutic indeces and are generally well tolerated. However, the combination of statins with mainly triglyceride-lowering fibrates, especially nicotinic acid or gemfibrozil, or potent cytochrome P450/p-glycoprotein

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inhibitors significantly increases the risk to develop myopathy such as potentially fatal rhabdomyolysis. A recent example stressing the clinical importance of statin/fibrate drug interactions is the removal of cerivastatin from the market on August 8, 2001 after at least 40 fatal cases of rhabdomyolysis were reported when cerivastatin was coadministered with the fibrate gemfibrozil. Although for each statin an equilibrium between both acid and lactone form exists in vivo, very little attention has been paid to the potential role of the lactones of statins administered as open acids (atorvastatin, cerivastatin, fluvastatin, pravastatin) in pharmacokinetic and pharmacodynamic drug interactions and toxicity.This is surprising since the lactone forms are considerably more lipophilic than the acid forms, and it seems reasonable to assume that their access and affinities to cytochrome P450 enzymes, transporters and their tissue distribution, e.g. into muscle cells, differs significantly from the acids. It is our hypothesis that the statin lactones play a key role in statin pharmacokinetics and toxicity. To identify the role of statin lactones in statin toxicity, we will assess both lactone pharmacokinetics and their pharmacodynamic effects on liver and muscle cell metabolism using magnetic resonance spectroscopy (MRS). It will be our primary goal to assess the mechanistic role of statin lactones in the pharmacokinetics, toxicity and drug-drug interactions of statins in comparison to their corresponding acids. Our secondary goal will be to compare the lactones/acids of the different statins with each other. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STATINS AND NON-CARDIAC ENDPOINTS Principal Investigator & Institution: Golomb, Beatrice A.; Assistant Professor; Medicine; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 920930934 Timing: Fiscal Year 2002; Project Start 20-AUG-1999; Project End 31-JUL-2004 Summary: (adapted from investigator's abstract): A relation of lowered cholesterol to increased aggressive behaviors (including suicide) and impaired cognition has been variably demonstrated and remains to be established or excluded with confidence. HMG-CoA reductase inhibitors ("statins") are the most widely used agents and their effects are of special interest. Purpose: To examine the effect of statins on aggressive responding, cognition, and serotonin in individuals with moderate LDL and no identified cardiovascular disease (CVD). Hypothesis: Statin therapy will increase aggressive responding on the PSAP (Point Subtraction Aggression paradigm, a standardized aggression measure that correlates with both violent behavior and serotonin); will reduce measures of cognition (including psychomotor speed and attention); and will change serotonin (gauged by whole blood serotonin), which may be a mediator of effects on behavior and perhaps cognition. Secondarily, it is hypothesized that simvastatin (lipophilic) will exert more potent effects on cognition (and perhaps aggression) than pravastatin (hydrophilic); that serotonin (5HT) changes will related to changes in aggressive responding and perhaps cognition; and that a "susceptible subset" may be defined by baseline characteristics including biochemistry, mood, personality, and extremes of cardiovascular reactivity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SYMPATHETIC CONTROL IN HEART FAILURE: A ROLE FOR STATINS Principal Investigator & Institution: Zucker, Irving H.; Theodore F. Hubbard Professor of Cardiov; Physiology and Biophysics; University of Nebraska Medical Center Omaha, Ne 681987835

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Timing: Fiscal Year 2002; Project Start 01-JUL-1987; Project End 30-JUN-2007 Summary: (provided by applicant): Sympatho-excitation along with general neurohumoral activation is a universal finding in the setting of chronic heart failure (CHF). Interruption of sympathetic nerve activity using beta blockers has been a standard therapeutic regimen for CHF patients for many years. However, the mechanisms responsible for sympatho-excitation in the CHF state are still unclear. Recently, it has been shown that several substances which are either increased or decreased in the CHF state act as modulators of sympathetic outflow. These substances include nitric oxide (NO), angiotensin II (Ang II) and endothelin-1 (ET-1). Recent animal and human studies have shown that the class of compounds known as HMG CoA reductase inhibitors or statins possess a variety of biological effects other than their ability to lower plasma cholesterol. These so called pleiotropic effects include lowering of arterial pressure, increasing production of endothelial NO, reducing Ang II receptors, reducing the production of ET-1 and scavenging of oxygen derived free radicals. Because of these actions we hypothesize that statins participate in sympatho-inhibition in the CHF state by virtue of several of the above effects. Preliminary data suggest that administration of simvastatin to rabbits with experimental CHF reduces resting renal sympathetic nerve activity (RSNA) and enhances baroreflex function. We propose a series of experiments to extend these preliminary studies and investigate the role of statins in sympathetic regulation in conscious rabbits with and without pacing-induced CHF. Rabbits will be treated with either simvastatin or pravastatin. Hemodynamics and RSNA will be measured as well as arterial baroreflex function. The role of NO will be determined by repeating experiments following peripheral and central blockade of nNOS. Central alterations in Ang II receptors and in ET-1 will be determined. Finally, the involvement of the GTP binding proteins of the Rho family will be determined in order to assess the role of these substances in mediating the enhancement of NO production by statins. These experiments will shed new light on central mechanisms of sympatho-excitation in the CHF state. The data accrued will have applicability to our understanding of autonomic regulation and therapeutics in this disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TDM & DRUG INTERACTIONS IN HIVINFECTED SUBSTANCE ABUSERS Principal Investigator & Institution: Morse, Gene D.; Chairman; Pharmacy Practice; State University of New York at Buffalo Suite 211 Ub Commons Buffalo, Ny 14228 Timing: Fiscal Year 2003; Project Start 15-JUN-2003; Project End 31-MAY-2007 Summary: (provided by applicant): This application describes an innovative approach to the rapid assessment of complex drug interactions between protease inhibitors and nonnucleoside reverse transcriptase inhibitors (NNRTIs), and commonly prescribed medications including methadone, ethinyl estradiol, fluconazole, pravastatin, and fluoxetine in HIV-infected, substance abusers The proposed methodology employs a Therapeutic Drug Monitoring (TDM) program that will facilitate rapid determination of ART in subjects receiving multiple interacting medications Specific aims 1) Implement a TDM program that will establish a mechanism to investigate protease inhibitor (PI) and NNRTI pharmacokinetics in HIV-infected, substance abusers receiving ART, determine drug exposure parameters (Cmin, AUC) and inhibitory quotients (IQs), 2) Determine the pharmacokinetics of selected interacting medications (methadone, ethinyl estradiol, fluconazole, pravastatin, fluoxetine) in HIV-infected, substance abusers receiving ART, 3) Determine in vitro and ex vivo total and unbound plasma concentrations of protease inhibitors and NNRTIs in HIV-infected, substance abusers utilizing novel analytical

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approaches including HPLC, LC-MS-MS and capillary electrophoresis, 4) Develop and validate a capillary electrophoresis assay capable of enantiomeric separation to enhance the pharmacokinetic analysis of interacting medications, 5) Examine pharmacogenetic factors that may identify individuals at greater risk for insufficient or excessive systemic drug exposure while receiving complex regimens with multiple drug-drug interactions The proposed TDM-drug-drug interaction program integrates a comprehensive antiretroviral clinical pharmacology research group, an HPLC/LC-MS analytical facility, a pharmacometrics laboratory, a web-based TDM enrollment infrastructure, and four HIV clinical centers caring for substance abusers Innovative pharmacokinetic and pharmacodynamic modeling approaches to assess complex drug-drug interaction analyses of PI and NNRTIs from HIV-infected substance abusers and non-substance abusers will be conducted. Clinical sites will enroll subjects while drug measurement and data analysis will be conducted at the central pharmacology laboratory. These studies will provide insight into clinical interactions that face clinicians and patients today, and identify priority drug interactions that require more traditional pharmacokinetic trials to identify specific mechanisms of interaction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “pravastatin” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for pravastatin in the PubMed Central database: •

A Prospective Study of Pravastatin in the Elderly at Risk (PROSPER): Screening Experience and Baseline Characteristics. by Ford I, Blauw GJ, Murphy MB, Shepherd J, Cobbe SM, Bollen EL, Buckley BM, Jukema JW, Hyland M, Gaw A, Lagaay AM, Perry IJ, Macfarlane P, Norrie J, Meinders AE, Sweeney BJ, Packard CJ, Westendorp RG, Twomey C, Stott DJ.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=134480

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Elderly patients with coronary artery disease: Is pravastatin an answer? by Chen BH.; 2001 Sep 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=81480

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.

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The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with pravastatin, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “pravastatin” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for pravastatin (hyperlinks lead to article summaries): •

A comparative study of the therapeutic effect of probucol and pravastatin on xanthelasma. Author(s): Fujita M, Shirai K. Source: The Journal of Dermatology. 1996 September; 23(9): 598-602. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8916658

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A comparison of estrogen replacement, pravastatin, and combined treatment for the management of hypercholesterolemia in postmenopausal women. Author(s): Davidson MH, Testolin LM, Maki KC, von Duvillard S, Drennan KB. Source: Archives of Internal Medicine. 1997 June 9; 157(11): 1186-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9183229

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A comparison of low versus standard dose pravastatin therapy for the prevention of cardiovascular events in the elderly: the pravastatin anti-atherosclerosis trial in the elderly (PATE). Author(s): Ito H, Ouchi Y, Ohashi Y, Saito Y, Ishikawa T, Nakamura H, Orimo H. Source: J Atheroscler Thromb. 2001; 8(2): 33-44. Erratum In: J Atheroscler Thromb 2001; 8(3): Following 100. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11770708

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A comparison of pravastatin and gemfibrozil in the treatment of dyslipoproteinemia in patients with non-insulin-dependent diabetes mellitus. Author(s): Schweitzer M, Tessier D, Vlahos WD, Leiter L, Collet JP, McQueen MJ, Harvey L, Alaupovic P. Source: Atherosclerosis. 2002 May; 162(1): 201-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11947915

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.

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A comparison of the effect of the 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase inhibitors simvastatin, lovastatin and pravastatin on leukaemic and normal bone marrow progenitors. Author(s): Newman A, Clutterbuck RD, Powles RL, Catovsky D, Millar JL. Source: Leukemia & Lymphoma. 1997 February; 24(5-6): 533-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9086443

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A comparison of the effects of simvastatin and pravastatin monotherapy on muscle histology and permeability in hypercholesterolaemic patients. Author(s): Contermans J, Smit JW, Bar PR, Erkelens DW. Source: British Journal of Clinical Pharmacology. 1995 February; 39(2): 135-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7742151

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A controlled trial of pravastatin vs probucol in the treatment of primary hypercholesterolemia. Author(s): Gomez-Perez FJ, Bustamante F, Vergara A, Villasenor J, Wong B, Rull JA. Source: Revista De Investigacion Clinica; Organo Del Hospital De Enfermedades De La Nutricion. 1992 January-March; 44(1): 53-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1523350

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A familial combined hyperlipidemic kindred with impaired apolipoprotein B catabolism. Kinetics of apolipoprotein B during placebo and pravastatin therapy. Author(s): Aguilar-Salinas CA, Hugh P, Barrett R, Pulai J, Zhu XL, Schonfeld G. Source: Arteriosclerosis, Thrombosis, and Vascular Biology. 1997 January; 17(1): 72-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9012640

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A multi-centre study of the efficacy and safety of pravastatin in hypercholesterolaemic patients with non-insulin-dependent diabetes mellitus. Author(s): Inoue Y, Kaku K, Okubo M, Hatao K, Hatao M, Kaneko T, Matsumura S, Ando S, Fujii S. Source: Current Medical Research and Opinion. 1994; 13(4): 187-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7882697

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A multinational study of the effects of low-dose pravastatin in patients with noninsulin-dependent diabetes mellitus and hypercholesterolemia. Pravastatin Multinational Study Group for Diabetes. Author(s): Behounek BD, McGovern ME, Kassler-Taub KB, Markowitz JS, Bergman M. Source: Clin Cardiol. 1994 October; 17(10): 558-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8001304

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A pharmacokinetic evaluation of pravastatin in middle-aged and elderly volunteers. Author(s): Sigurbjornsson S, Kjartansdottir T, Johannsson M, Kristinsson J, Sigurdsson G. Source: Eur J Drug Metab Pharmacokinet. 1998 January-March; 23(1): 13-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9625267

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A randomized, double-blind trial comparing the efficacy and safety of pitavastatin versus pravastatin in patients with primary hypercholesterolemia. Author(s): Saito Y, Yamada N, Teramoto T, Itakura H, Hata Y, Nakaya N, Mabuchi H, Tushima M, Sasaki J, Ogawa N, Goto Y. Source: Atherosclerosis. 2002 June; 162(2): 373-9. Erratum In: Atherosclerosis. 2003 Jun; 168(2): 401. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11996957

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Abnormal lipoprotein (a) and lipid profiles in renal allograft recipients: effects of treatment with pravastatin. Author(s): Lye WC, Hughes K, Leong SO, Tan CC, Lee EJ. Source: Transplantation Proceedings. 1995 February; 27(1): 977-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7879252

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Accumulation of lovastatin, but not pravastatin, in the blood of cyclosporine-treated kidney graft patients after multiple doses. Author(s): Olbricht C, Wanner C, Eisenhauer T, Kliem V, Doll R, Boddaert M, O'Grady P, Krekler M, Mangold B, Christians U. Source: Clinical Pharmacology and Therapeutics. 1997 September; 62(3): 311-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9333107

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Action of lovastatin, simvastatin, and pravastatin on sterol synthesis and their antiproliferative effect in cultured myoblasts from human striated muscle. Author(s): van Vliet AK, Negre-Aminou P, van Thiel GC, Bolhuis PA, Cohen LH. Source: Biochemical Pharmacology. 1996 November 8; 52(9): 1387-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8937448

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Acute cholestatic hepatitis associated with pravastatin. Author(s): Hartleb M, Rymarczyk G, Januszewski K. Source: The American Journal of Gastroenterology. 1999 May; 94(5): 1388-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10235223

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Acute pancreatitis due to pravastatin therapy. Author(s): Anagnostopoulos GK, Tsiakos S, Margantinis G, Kostopoulos P, Arvanitidis D. Source: Jop [electronic Resource] : Journal of the Pancreas. 2003 May; 4(3): 129-32. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12743419

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Additional reduction in blood pressure after cholesterol-lowering treatment by statins (lovastatin or pravastatin) in hypercholesterolemic patients using angiotensinconverting enzyme inhibitors (enalapril or lisinopril). Author(s): Sposito AC, Mansur AP, Coelho OR, Nicolau JC, Ramires JA. Source: The American Journal of Cardiology. 1999 May 15; 83(10): 1497-9, A8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10335771

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Additive benefits of pravastatin and aspirin to decrease risks of cardiovascular disease: randomized and observational comparisons of secondary prevention trials and their meta-analyses. Author(s): Hennekens CH, Sacks FM, Tonkin A, Jukema JW, Byington RP, Pitt B, Berry DA, Berry SM, Ford NF, Walker AJ, Natarajan K, Sheng-Lin C, Fiedorek FT, Belder R. Source: Archives of Internal Medicine. 2004 January 12; 164(1): 40-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14718320

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Allergy to pravastatin. Author(s): de Boer EM, Bruynzeel DP. Source: Contact Dermatitis. 1994 April; 30(4): 238. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8033551

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Altered disposition of pravastatin following concomitant drug therapy with cyclosporin A in transplant recipients. Author(s): Regazzi MB, Iacona I, Campana C, Raddato V, Lesi C, Perani G, Gavazzi A, Vigano M. Source: Transplantation Proceedings. 1993 August; 25(4): 2732-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8356729

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Altitude-induced migraine headache secondary to pravastatin: case report. Author(s): Ramsey CS, Snyder QC. Source: Aviation, Space, and Environmental Medicine. 1998 June; 69(6): 603-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9641408

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Amelioration of hypercholesterolaemia by HMG-CoA reductase inhibitor (Pravastatin) improved platelet hyperaggregability in nephrotic patients. Author(s): Yashiro M, Muso E, Shio H, Sasayama S. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 1994; 9(12): 1842-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7708285

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An automated method for the simultaneous determination of pravastatin and its main metabolite in human plasma by high-performance liquid chromatography/atmospheric pressure chemical ionization mass spectrometry. Author(s): Kawabata K, Matsushima N, Sasahara K. Source: Biomedical Chromatography : Bmc. 1998 September-October; 12(5): 271-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9787898

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Apo A-I promoter polymorphism influences basal HDL-cholesterol and its response to pravastatin therapy. Author(s): Lahoz C, Pena R, Mostaza JM, Jimenez J, Subirats E, Pinto X, Taboada M, Lopez-Pastor A; RAP Study Group. Source: Atherosclerosis. 2003 June; 168(2): 289-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12801612

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Apolipoprotein(a) polymorphism predicts the increase of Lp(a) by pravastatin in patients with familial hypercholesterolaemia treated with bile acid sequestration. Author(s): Klausen IC, Gerdes LU, Meinertz H, Hansen FA, Faergeman O. Source: European Journal of Clinical Investigation. 1993 April; 23(4): 240-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8500516

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ARBITER: Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol: a randomized trial comparing the effects of atorvastatin and pravastatin on carotid intima medial thickness. Author(s): Taylor AJ, Kent SM, Flaherty PJ, Coyle LC, Markwood TT, Vernalis MN. Source: Circulation. 2002 October 15; 106(16): 2055-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12379573

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Are statins anti-inflammatory? Issues in the design and conduct of the pravastatin inflammation C-reactive protein evaluation. Author(s): Ridker PM. Source: Current Cardiology Reports. 2000 July; 2(4): 269-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10953258

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Association of pravastatin and left ventricular mass in hypercholesterolemic patients: role of 8-iso-prostaglandin f2alpha formation. Author(s): Lee TM, Chou TF, Tsai CH. Source: Journal of Cardiovascular Pharmacology. 2002 December; 40(6): 868-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12451319

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Atorvastatin plus pravastatin for the treatment of heterozygous familial hypercholesterolaemia--a pilot study. Author(s): Athyros VG, Papageorgiou AA, Demitriadis DS, Kontopoulos AG. Source: Current Medical Research and Opinion. 2001; 17(4): 267-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11922400

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Beneficial effects of pravastatin in peri- and postmenopausal hyperlipidemic women: a 5-year study on serum lipid and sex hormone levels. Author(s): Ushiroyama T, Ikeda A, Ueki M. Source: Maturitas. 2001 January 31; 37(3): 201-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11173182

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Beneficial effects of pravastatin on fasting hyperinsulinemia in elderly hypertensive hypercholesterolemic subjects. Author(s): Chan P, Tomlinson B, Lee CB, Pan WH, Lee YS. Source: Hypertension. 1996 October; 28(4): 647-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8843892

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Beneficial effects of simvastatin and pravastatin on cardiac allograft rejection and survival. Author(s): Conraads V. Source: Journal of the American College of Cardiology. 2003 June 4; 41(11): 2104; Author Reply 2104. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12798591

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Benefits of pravastatin on cardiovascular events and mortality in older patients with coronary heart disease are equal to or exceed those seen in younger patients: Results from the LIPID trial. Author(s): Hunt D, Young P, Simes J, Hague W, Mann S, Owensby D, Lane G, Tonkin A. Source: Annals of Internal Medicine. 2001 May 15; 134(10): 931-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11352694

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Biotransformation of pravastatin sodium in humans. Author(s): Everett DW, Chando TJ, Didonato GC, Singhvi SM, Pan HY, Weinstein SH. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 1991 JulyAugust; 19(4): 740-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1680649

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B-mode ultrasound assessment of pravastatin treatment effect on carotid and femoral artery walls and its correlations with coronary arteriographic findings: a report of the Regression Growth Evaluation Statin Study (REGRESS). Author(s): de Groot E, Jukema JW, Montauban van Swijndregt AD, Zwinderman AH, Ackerstaff RG, van der Steen AF, Bom N, Lie KI, Bruschke AV. Source: Journal of the American College of Cardiology. 1998 June; 31(7): 1561-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9626835

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By the way, doctor. I have high cholesterol, and have been taking Mevacor (lovastatin) for two years. Recently, I was switched to Pravachol (pravastatin) because my insurance company would no longer pay for Mevacor. Is it as good? Author(s): Nicholson CR. Source: Harvard Women's Health Watch. 1999 June; 6(10): 8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10233830

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Cerivastatin versus branded pravastatin in the treatment of primary hypercholesterolemia in primary care practice in Canada: a one-year, open-label, randomized, comparative study of efficacy, safety, and cost-effectiveness. Author(s): McPherson R, Hanna K, Agro A, Braeken A; Canadian Cerivastatin Study Group. Source: Clinical Therapeutics. 2001 September; 23(9): 1492-507. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11589262

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Cholestasis associated with the use of pravastatin sodium. Author(s): Batey RG, Harvey M. Source: The Medical Journal of Australia. 2002 June 3; 176(11): 561. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12064992

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Cholesterol lowering with pravastatin improves resistance artery endothelial function: report of six subjects with normal coronary arteriograms. Author(s): Houghton JL, Pearson TA, Reed RG, Torosoff MT, Henches NL, Kuhner PA, Philbin EF. Source: Chest. 2000 September; 118(3): 756-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10988199

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Cholesterol-lowering therapy with pravastatin in patients with average cholesterol levels and established ischaemic heart disease: is it cost-effective? Author(s): Glasziou PP, Eckermann SD, Mulray SE, Simes RJ, Martin AJ, Kirby AC, Hall JP, Caleo S, White HD, Tonkin AM. Source: The Medical Journal of Australia. 2002 October 21; 177(8): 428-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12381252

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Cholesteryl ester transfer in hypercholesterolaemia: fasting and postprandial studies with and without pravastatin. Author(s): Contacos C, Barter PJ, Vrga L, Sullivan DR. Source: Atherosclerosis. 1998 November; 141(1): 87-98. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9863541

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Clinical pharmacokinetics of pravastatin: mechanisms of pharmacokinetic events. Author(s): Hatanaka T. Source: Clinical Pharmacokinetics. 2000 December; 39(6): 397-412. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11192473

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Clinical pharmacology of pravastatin, a selective inhibitor of HMG-CoA reductase. Author(s): Pan HY. Source: European Journal of Clinical Pharmacology. 1991; 40 Suppl 1: S15-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1904355

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Combined treatment with chenodeoxycholic acid and pravastatin improves plasma cholestanol levels associated with marked regression of tendon xanthomas in cerebrotendinous xanthomatosis. Author(s): Nakamura T, Matsuzawa Y, Takemura K, Kubo M, Miki H, Tarui S. Source: Metabolism: Clinical and Experimental. 1991 July; 40(7): 741-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1908036

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Combined treatment with low-dose pravastatin and fish oil in post-renal transplantation dislipidemia. Author(s): Grekas D, Kassimatis E, Makedou A, Bacharaki D, Bamichas G, Tourkantonis A. Source: Nephron. 2001 August; 88(4): 329-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11474227

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Comment: possible interaction between nefazodone and pravastatin. Author(s): Bottorf MB. Source: The Annals of Pharmacotherapy. 2000 April; 34(4): 538, 541. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10772447

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Compactin and simvastatin, but not pravastatin, induce bone morphogenetic protein2 in human osteosarcoma cells. Author(s): Sugiyama M, Kodama T, Konishi K, Abe K, Asami S, Oikawa S. Source: Biochemical and Biophysical Research Communications. 2000 May 19; 271(3): 688-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10814523

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Comparative beneficial effects of simvastatin and pravastatin on cardiac allograft rejection and survival. Author(s): Mehra MR, Uber PA, Vivekananthan K, Solis S, Scott RL, Park MH, Milani RV, Lavie CJ. Source: Journal of the American College of Cardiology. 2002 November 6; 40(9): 1609-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12427413

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Comparative dose efficacy study of atorvastatin versus simvastatin, pravastatin, lovastatin, and fluvastatin in patients with hypercholesterolemia (the CURVES study) Author(s): Jones P, Kafonek S, Laurora I, Hunninghake D. Source: The American Journal of Cardiology. 1998 March 1; 81(5): 582-7. Erratum In: Am J Cardiol 1998 July 1; 82(1): 128. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9514454

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Comparative effects of two HMG-CoA reductase inhibitors (lovastatin and pravastatin) on serum lipids and lipoproteins. Author(s): Richter WO, Jacob BG, Schwandt P. Source: Int J Tissue React. 1991; 13(2): 107-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1955291

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Comparative efficacy and tolerability of low-dose pravastatin versus lovastatin in patients with hypercholesterolemia. Author(s): Strauss WE, Lapsley D, Gaziano JM. Source: American Heart Journal. 1999 March; 137(3): 458-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10047626

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Comparative efficacy of once-daily versus twice-daily pravastatin in primary hypercholesterolemia. Author(s): Pan HY, DeVault AR, Brescia D, Willard DA. Source: Clinical Therapeutics. 1991 May-June; 13(3): 368-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1954638

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Comparative efficacy study of atorvastatin vs simvastatin, pravastatin, lovastatin and placebo in type 2 diabetic patients with hypercholesterolaemia. Author(s): Gentile S, Turco S, Guarino G, Sasso CF, Amodio M, Magliano P, Salvatore T, Corigliano G, Agrusta M, De Simone G, Gaeta I, Oliviero B, Torella R. Source: Diabetes, Obesity & Metabolism. 2000 December; 2(6): 355-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11225965

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Comparative pharmacokinetics of lovastatin, simvastatin and pravastatin in humans. Author(s): Pentikainen PJ, Saraheimo M, Schwartz JI, Amin RD, Schwartz MS, BrunnerFerber F, Rogers JD. Source: Journal of Clinical Pharmacology. 1992 February; 32(2): 136-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1613123

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Comparison of cytochrome P-450-dependent metabolism and drug interactions of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors lovastatin and pravastatin in the liver. Author(s): Jacobsen W, Kirchner G, Hallensleben K, Mancinelli L, Deters M, Hackbarth I, Benet LZ, Sewing KF, Christians U. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 1999 February; 27(2): 173-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9929499

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Comparison of low-density lipoprotein cholesterol lowering by pravastatin to <100 mg/dl versus >100 mg/dl on brachial artery vasoreactivity in patients with severe hypercholesterolemia and previous atherosclerotic events or diabetes mellitus. Author(s): Lekakis JP, Papamichael CM, Barbaki P, Papaioannou TG, Stamatelopoulos KS, Dagre AG, Stamatelopoulos SF. Source: The American Journal of Cardiology. 2002 April 1; 89(7): 857-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11909575

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Comparison of micronized fenofibrate and pravastatin in patients with primary hyperlipidemia. Author(s): Ducobu J, VanHaelst L, Salomon H. Source: Journal of Cardiovascular Pharmacology. 2003 January; 41(1): 60-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12500022

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Comparison of the effects of pravastatin and lovastatin on sleep disturbance in hypercholesterolemic subjects. Author(s): Ehrenberg BL, Lamon-Fava S, Corbett KE, McNamara JR, Dallal GE, Schaefer EJ. Source: Sleep. 1999 February 1; 22(1): 117-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9989373

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Comparison of the effects of simvastatin and pravastatin on acute rejection episodes in renal transplant patients. Author(s): Tuncer M, Suleymanlar G, Ersoy FF, Yakupoglu G. Source: Transplantation Proceedings. 2000 May; 32(3): 622-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10812143

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Pravastatin

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Comparison of the efficacy and safety of pravastatin and simvastatin in heart transplantation. Author(s): Vivekananthan K, Mehra MR, Uber PA, DeGruiter H, Lavie CJ, Milani RV. Source: J Assoc Physicians India. 2002 May; 50(5): 682-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12186124

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Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR* Trial). Author(s): Jones PH, Davidson MH, Stein EA, Bays HE, McKenney JM, Miller E, Cain VA, Blasetto JW; STELLAR Study Group. Source: The American Journal of Cardiology. 2003 July 15; 92(2): 152-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12860216

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Comparison of the short-term efficacy and tolerability of lovastatin and pravastatin in the management of primary hypercholesterolemia. Author(s): McPherson R, Bedard J, Connelly P, Curnew G, Davignon J, Echenberg D, Lavin P, Leiter L, Lenis J, McQueen M, et al. Source: Clinical Therapeutics. 1992 March-April; 14(2): 276-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1611649

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Comparisons of effects of statins (atorvastatin, fluvastatin, lovastatin, pravastatin, and simvastatin) on fasting and postprandial lipoproteins in patients with coronary heart disease versus control subjects. Author(s): Schaefer EJ, McNamara JR, Tayler T, Daly JA, Gleason JL, Seman LJ, Ferrari A, Rubenstein JJ. Source: The American Journal of Cardiology. 2004 January 1; 93(1): 31-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14697462

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Concentrations of pravastatin and lovastatin in cerebrospinal fluid in healthy subjects. Author(s): Botti RE, Triscari J, Pan HY, Zayat J. Source: Clinical Neuropharmacology. 1991 June; 14(3): 256-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1906375

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Coronary heart disease in patients with low LDL-cholesterol: benefit of pravastatin in diabetics and enhanced role for HDL-cholesterol and triglycerides as risk factors. Author(s): Sacks FM, Tonkin AM, Craven T, Pfeffer MA, Shepherd J, Keech A, Furberg CD, Braunwald E. Source: Circulation. 2002 March 26; 105(12): 1424-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11914249

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Cost-effectiveness of pravastatin therapy for survivors of myocardial infarction with average cholesterol levels. Author(s): Tsevat J, Kuntz KM, Orav EJ, Weinstein MC, Sacks FM, Goldman L. Source: American Heart Journal. 2001 May; 141(5): 727-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11320359

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Decrease in all-cause and CHD mortality with pravastatin over a broad range of initial cholesterol levels. Author(s): Goodwin L. Source: J Insur Med. 1998; 30(4): 276-7. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10537938

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Decreased albuminuria by pravastatin in hyperlipidemic diabetics. Author(s): Shoji T, Nishizawa Y, Toyokawa A, Kawagishi T, Okuno Y, Morii H. Source: Nephron. 1991; 59(4): 664-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1766510

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Defined daily doses in relation to hypolipidaemic efficacy of lovastatin, pravastatin, and simvastatin. Author(s): Illingworth DR, Erkelens DW, Keller U, Thompson GR, Tikkanen MJ. Source: Lancet. 1994 June 18; 343(8912): 1554-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7911877

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Depressive symptoms and pravastatin. Author(s): Kassler-Taub K, Woodward T, Markowitz JS. Source: Lancet. 1993 February 6; 341(8841): 371-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8094134

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Depressive symptoms in hypercholesterolaemic patients treated with pravastatin. Author(s): Lechleitner M, Hoppichler F, Konwalinka G, Patsch JR, Braunsteiner H. Source: Lancet. 1992 October 10; 340(8824): 910. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1357315

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Design and rationale of the ARBITER trial (Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol)--a randomized trial comparing the effects of atorvastatin and pravastatin on carotid artery intima-media thickness. Author(s): Markwood TT, Kent SM, Coyle LC, Flaherty PJ, O'Malley PG, Taylor AJ. Source: American Heart Journal. 2001 March; 141(3): 342-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11231429

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Design and recruitment in the United States of a multicenter quantitative angiographic trial of pravastatin to limit atherosclerosis in the coronary arteries (PLAC I). Author(s): Pitt B, Ellis SG, Mancini GB, Rosman HS, McGovern ME. Source: The American Journal of Cardiology. 1993 July 1; 72(1): 31-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8517425

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Design of a cost-effectiveness study within a randomized trial: the LIPID Trial for Secondary Prevention of IHD. Long-term Intervention with Pravastatin in Ischemic Heart disease. Author(s): Glasziou PP, Simes RJ, Hall J, Donaldson C. Source: Controlled Clinical Trials. 1997 October; 18(5): 464-76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9315428

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Design of the Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE IT)-TIMI 22 trial. Author(s): Cannon CP, McCabe CH, Belder R, Breen J, Braunwald E. Source: The American Journal of Cardiology. 2002 April 1; 89(7): 860-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11909576

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Determination of pravastatin by high performance liquid chromatography. Author(s): Siekmeier R, Gross W, Marz W. Source: Int J Clin Pharmacol Ther. 2000 September; 38(9): 419-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11020028

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Determination of pravastatin in human plasma by high-performance liquid chromatography with ultraviolet detection. Author(s): Otter K, Mignat C. Source: J Chromatogr B Biomed Sci Appl. 1998 April 24; 708(1-2): 235-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9653968

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Determination of pravastatin sodium and its isomeric metabolite in human urine by HPLC with UV detection. Author(s): Whigan DB, Ivashkiv E, Cohen AI. Source: Journal of Pharmaceutical and Biomedical Analysis. 1989; 7(7): 907-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2518755

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Determination of pravastatin sodium and its major metabolites in human serum/plasma by capillary gas chromatography/negative ion chemical ionization mass spectrometry. Author(s): Funke PT, Ivashkiv E, Arnold ME, Cohen AI. Source: Biomed Environ Mass Spectrom. 1989 October; 18(10): 904-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2508807

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Determination of the HMG-CoA reductase inhibitors simvastatin, lovastatin, and pravastatin in plasma by gas chromatography/chemical ionization mass spectrometry. Author(s): Morris MJ, Gilbert JD, Hsieh JY, Matuszewski BK, Ramjit HG, Bayne WF. Source: Biol Mass Spectrom. 1993 January; 22(1): 1-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8431499

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Diet and pravastatin in moderate hypercholesterolaemia: a randomized trial in 215 middle-aged men free from cardiovascular disease. Author(s): Bak AA, Huizer J, Leijten PA, Rila H, Grobbee DE. Source: Journal of Internal Medicine. 1998 November; 244(5): 371-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9845852

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Dietary advice with or without pravastatin for the management of hypercholesterolaemia associated with protease inhibitor therapy. Author(s): Moyle GJ, Lloyd M, Reynolds B, Baldwin C, Mandalia S, Gazzard BG. Source: Aids (London, England). 2001 August 17; 15(12): 1503-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11504982

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Different effects of simvastatin and pravastatin on adrenal sensitivity to angiotensin II. Author(s): Sugimoto K, Fujimura A. Source: British Journal of Clinical Pharmacology. 2003 December; 56(6): 696-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14616433

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Different effects of St John's wort on the pharmacokinetics of simvastatin and pravastatin. Author(s): Sugimoto K, Ohmori M, Tsuruoka S, Nishiki K, Kawaguchi A, Harada K, Arakawa M, Sakamoto K, Masada M, Miyamori I, Fujimura A. Source: Clinical Pharmacology and Therapeutics. 2001 December; 70(6): 518-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11753267

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Different effects of the hypolipidemic drugs pravastatin and lovastatin on the cholesterol biosynthesis of the human ocular lens in organ culture and on the cholesterol content of the rat lens in vivo. Author(s): de Vries AC, Cohen LH. Source: Biochimica Et Biophysica Acta. 1993 March 17; 1167(1): 63-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8461334

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Differing effects of low-dose estrogen-progestin therapy and pravastatin in postmenopausal hypercholesterolemic women. Author(s): Davis SR, Goldstat R, Newman A, Berry K, Burger HG, Meredith I, Koch K. Source: Climacteric : the Journal of the International Menopause Society. 2002 December; 5(4): 341-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12626213

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Disposition of pravastatin sodium, a tissue-selective HMG-CoA reductase inhibitor, in healthy subjects. Author(s): Singhvi SM, Pan HY, Morrison RA, Willard DA. Source: British Journal of Clinical Pharmacology. 1990 February; 29(2): 239-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2106337

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Do cholesterol-lowering agents affect brain activity? A comparison of simvastatin, pravastatin, and placebo in healthy volunteers. Author(s): Harrison RW, Ashton CH. Source: British Journal of Clinical Pharmacology. 1994 March; 37(3): 231-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8198930

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Does pravastatin affect circulating levels of soluble TNF receptor 2 in hypercholesterolemic patients? Author(s): Ando H, Takamura T, Kobayashi K, Misu H, Osawa K. Source: Atherosclerosis. 2003 February; 166(2): 413-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12535759

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Does the HMG-CoA reductase inhibitor pravastatin influence nucleation of cholesterol crystals in supersaturated model bile? Author(s): Smit JW, Van Erpecum KJ, Gadella MM, Van de Heyning BJ, Van BergeHenegouwen GP. Source: European Journal of Gastroenterology & Hepatology. 1996 March; 8(3): 197-200. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8724016

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Dose-dependent hypolipidemic effect of an inhibitor of HMG-CoA reductase, pravastatin (CS-514), in hypercholesterolemic subjects. A double blind test. Author(s): Saito Y, Goto Y, Nakaya N, Hata Y, Homma Y, Naito C, Hayashi H, Ito H, Yamamoto M, Takeuchi I, et al. Source: Atherosclerosis. 1988 August; 72(2-3): 205-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3145746

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Double-masked comparison of the quality of life of hypercholesterolemic men treated with simvastatin or pravastatin. International Quality of Life Multicenter Group. Author(s): Seed M, Weir MR. Source: Clinical Therapeutics. 1999 October; 21(10): 1758-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10566571

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Drugs recently released in Belgium. Ibopamine--pravastatin. Author(s): Harvengt C. Source: Acta Clin Belg. 1993; 48(1): 54-7. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8098890

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Early use of pravastatin in patients with acute myocardial infarction undergoing coronary angioplasty. Author(s): Kayikcioglu M, Can L, Kultursay H, Payzin S, Turkoglu C. Source: Acta Cardiol. 2002 August; 57(4): 295-302. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12222700

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Effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor pravastatin on urinary 6 beta-hydroxycortisol excretion: a preliminary study. Author(s): Karayalcin U, Takeda Y, Miyamori I, Morise T, Takeda R. Source: Steroids. 1991 December; 56(12): 598-600. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1819871

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Effect of apoE genotype on the hypolipidaemic response to pravastatin in an outpatient setting. Author(s): Pena R, Lahoz C, Mostaza JM, Jimenez J, Subirats E, Pinto X, Taboada M, Lopez-Pastor A; Rap Study Group. Source: Journal of Internal Medicine. 2002 June; 251(6): 518-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12028507

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Effect of atorvastatin and pravastatin on serum C-reactive protein. Author(s): Kent SM, Flaherty PJ, Coyle LC, Markwood TT, Taylor AJ. Source: American Heart Journal. 2003 February; 145(2): E8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12595863

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Effect of pravastatin on apolipoproteins B and C-III in very-low-density lipoproteins and low-density lipoproteins. Author(s): Sacks FM, Alaupovic P, Moye LA. Source: The American Journal of Cardiology. 2002 July 15; 90(2): 165-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12106851

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Effect of pravastatin on cardiovascular events and mortality in 1516 women with coronary heart disease: results from the Long-Term Intervention with Pravastatin in Ischemic Disease (LIPID) study. Author(s): Hague W, Forder P, Simes J, Hunt D, Tonkin A; LIPID Investigators. Source: American Heart Journal. 2003 April; 145(4): 643-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12679760

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Effect of pravastatin on coronary plaque volume. Author(s): Ishikawa K, Tani S, Watanabe I, Matsumoto M, Furukawa K, Nomoto K, Nomoto K, Kushiro T, Nagao K, Kanmatsuse K. Source: The American Journal of Cardiology. 2003 October 15; 92(8): 975-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14556877

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Effect of pravastatin on intermediate-density and low-density lipoproteins containing apolipoprotein CIII in patients with diabetes mellitus. Author(s): Lee SJ, Sacks FM. Source: The American Journal of Cardiology. 2003 July 15; 92(2): 121-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12860210

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Effect of pravastatin on LDL particle concentration as determined by NMR spectroscopy: a substudy of a randomized placebo controlled trial. Author(s): Blake GJ, Albert MA, Rifai N, Ridker PM. Source: European Heart Journal. 2003 October; 24(20): 1843-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14563343

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Effect of pravastatin on loss of renal function in people with moderate chronic renal insufficiency and cardiovascular disease. Author(s): Tonelli M, Moye L, Sacks FM, Cole T, Curhan GC; Cholesterol and Recurrent Events Trial Investigators. Source: Journal of the American Society of Nephrology : Jasn. 2003 June; 14(6): 1605-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12761262

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Effect of pravastatin on proteinuria in patients with well-controlled hypertension. Author(s): Lee TM, Su SF, Tsai CH. Source: Hypertension. 2002 July; 40(1): 67-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12105140

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Effect of pravastatin on serum lipids, apolipoproteins and lipoprotein (a) in patients with non-insulin dependent diabetes mellitus. Author(s): Umeda F, Watanabe J, Inoue K, Hisatomi A, Mimura K, Yamauchi T, Sako Y, Kunisaki M, Tajiri Y, Nawata H. Source: Endocrinol Jpn. 1992 February; 39(1): 45-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1535040

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Effect of pravastatin treatment on the evolution of extracoronary atherosclerosis in renal transplant patients. Author(s): Cofan F, Gilabert R, Zambon D, Nunez I, Ros E, Cofan M, Campistol JM, Bru C, Oppenheimer F. Source: Transplantation Proceedings. 2002 February; 34(1): 384-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11959338

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Effect of pravastatin-induced LDL-cholesterol reduction on coronary heart disease and cerebrovascular disease in Japanese: Hokuriku lipid coronary heart disease study-pravastatin atherosclerosis trial (Holicos-PAT). Author(s): Koizumi J, Shimizu M, Miyamoto S, Origasa H, Mabuchi H. Source: J Atheroscler Thromb. 2002; 9(5): 251-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12409635

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Effects of bezafibrate and pravastatin on remnant-like lipoprotein particles and lipoprotein subclasses in type 2 diabetes. Author(s): Kazama H, Usui S, Okazaki M, Hosoi T, Ito H, Orimo H. Source: Diabetes Research and Clinical Practice. 2003 March; 59(3): 181-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12590014

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Effects of combined treatment with pravastatin and ursodeoxycholic acid on hepatic cholesterol metabolism. Author(s): Hillebrant CG, Nyberg B, Gustafsson U, Sahlin S, Bjorkhem I, Rudling M, Einarsson C. Source: European Journal of Clinical Investigation. 2002 July; 32(7): 528-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12153554

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Effects of lovastatin and pravastatin on sleep efficiency and sleep stages. Author(s): Vgontzas AN, Kales A, Bixler EO, Manfredi RL, Tyson KL. Source: Clinical Pharmacology and Therapeutics. 1991 December; 50(6): 730-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1752118

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Effects of pravastatin (CS-514) on biliary lipid metabolism in patients with hyperlipidemia. Author(s): Horiuchi I, Ohya T, Tazuma S, Mizuno T, Takizawa I, Kajiyama G. Source: Metabolism: Clinical and Experimental. 1991 March; 40(3): 226-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1900342

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Effects of pravastatin and cholestyramine on gonadal and adrenal steroid production in familial hypercholesterolaemia. Author(s): Jay RH, Sturley RH, Stirling C, McGarrigle HH, Katz M, Reckless JP, Betteridge DJ. Source: British Journal of Clinical Pharmacology. 1991 October; 32(4): 417-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1958433

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Effects of pravastatin and cholestyramine on products of the mevalonate pathway in familial hypercholesterolemia. Author(s): Elmberger PG, Kalen A, Lund E, Reihner E, Eriksson M, Berglund L, Angelin B, Dallner G. Source: Journal of Lipid Research. 1991 June; 32(6): 935-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1940625

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Effects of pravastatin in the elderly. Author(s): Iwata H, Aoyama T, Kami M. Source: Annals of Internal Medicine. 2002 June 4; 136(11): W2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12044146

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Effects of pravastatin on exercise electrocardiography test performance and cardiovascular mortality and morbidity in patients with hypercholesterolemia: Lipid Intervention Study in Kyoto. Author(s): Sasaki S, Nakagawa M, Nakata T, Azuma A, Sawada S, Takeda K, Asayama J; Lipid Intrvention Study in Kyoto. Source: Circulation Journal : Official Journal of the Japanese Circulation Society. 2002 January; 66(1): 47-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11999665

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Effects of pravastatin on serum lipids and apolipoproteins in hyperlipidemia of the nephrotic syndrome. Author(s): Tokoo M, Oguchi H, Terashima M, Tokunaga S, Miyasaka M, Hora K, Higuchi M, Yoshie T, Furuta S. Source: Nippon Jinzo Gakkai Shi. 1992 April; 34(4): 397-403. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1635284

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Effects of pravastatin, a new HMG-CoA reductase inhibitor, on vitamin D synthesis in man. Author(s): Dobs AS, Levine MA, Margolis S. Source: Metabolism: Clinical and Experimental. 1991 May; 40(5): 524-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1902546

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Effects of probucol and pravastatin on common carotid atherosclerosis in patients with asymptomatic hypercholesterolemia. Fukuoka Atherosclerosis Trial (FAST). Author(s): Sawayama Y, Shimizu C, Maeda N, Tatsukawa M, Kinukawa N, Koyanagi S, Kashiwagi S, Hayashi J. Source: Journal of the American College of Cardiology. 2002 February 20; 39(4): 610-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11849859

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Effects of simvastatin and pravastatin on peroxidation of erythrocyte plasma membrane lipids in patients with type 2 hypercholesterolemia. Author(s): Koter M, Franiak I, Broncel M, Chojnowska-Jezierska J. Source: Canadian Journal of Physiology and Pharmacology. 2003 May; 81(5): 485-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12774855

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Efficacy and safety of ezetimibe coadministered with pravastatin in patients with primary hypercholesterolemia: a prospective, randomized, double-blind trial. Author(s): Melani L, Mills R, Hassman D, Lipetz R, Lipka L, LeBeaut A, Suresh R, Mukhopadhyay P, Veltri E; Ezetimibe Study Group. Source: European Heart Journal. 2003 April; 24(8): 717-28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12713766

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Efficacy and safety of rosuvastatin compared with pravastatin and simvastatin in patients with hypercholesterolemia: a randomized, double-blind, 52-week trial. Author(s): Brown WV, Bays HE, Hassman DR, McKenney J, Chitra R, Hutchinson H, Miller E; Rosuvastatin Study Group. Source: American Heart Journal. 2002 December; 144(6): 1036-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12486428

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Efficacy of pravastatin as a hypolipidemic agent in patients with polygenic hypercholesterolemia. Author(s): Aldrete-Velasco J, Casanova JM, Mejia P, Martinez P. Source: Archives of Medical Research. 1992 Autumn; 23(3): 117-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1308800

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Endothelial nitric oxide synthase genotype modulates the improvement of coronary blood flow by pravastatin: a placebo-controlled PET study. Author(s): Kunnas TA, Lehtimaki T, Laaksonen R, Ilveskoski E, Janatuinen T, Vesalainen R, Nuutila P, Karhunen PJ, Knuuti J, Nikkari ST. Source: Journal of Molecular Medicine (Berlin, Germany). 2002 December; 80(12): 802-7. Epub 2002 November 22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12483466

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Factors affecting low-density lipoprotein and high-density lipoprotein cholesterol response to pravastatin in the West Of Scotland Coronary Prevention Study (WOSCOPS). Author(s): Streja L, Packard CJ, Shepherd J, Cobbe S, Ford I; WOSCOPS Group. Source: The American Journal of Cardiology. 2002 October 1; 90(7): 731-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12356386

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FDA advisers vote against OTC Pravachol. Author(s): Walczak IM. Source: Diabetes Technology & Therapeutics. 2000 Autumn; 2(3): 483-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11467352

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Fluvastatin versus pravastatin. Author(s): Chilton R. Source: The American Journal of Cardiology. 1996 July 1; 78(1): 127. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8712106

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Functional evaluation of lipid-lowering therapy by pravastatin in the Regression Growth Evaluation Statin Study (REGRESS) Author(s): Aengevaeren WR, Uijen GJ, Jukema JW, Bruschke AV, van der Werf T. Source: Circulation. 1997 July 15; 96(2): 429-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9244208

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Functional evaluation of lipid-lowering therapy by pravastatin. Author(s): Schoebel FC, Jax TW, Strauer BE, Leschke M. Source: Circulation. 1998 May 12; 97(18): 1874-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9603548

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Gastrointestinal absorption of pravastatin in healthy subjects. Author(s): Triscari J, O'Donnell D, Zinny M, Pan HY. Source: Journal of Clinical Pharmacology. 1995 February; 35(2): 142-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7751423

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Gastrointestinal cancer and the long-term use of pravastatin in the elderly. Author(s): Devroey D, Buntinx F, Betz W, Vandevoorde J, Kartounian J. Source: Acta Oncologica (Stockholm, Sweden). 2003; 42(4): 347-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12899509

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Gemfibrozil increases plasma pravastatin concentrations and reduces pravastatin renal clearance. Author(s): Kyrklund C, Backman JT, Neuvonen M, Neuvonen PJ. Source: Clinical Pharmacology and Therapeutics. 2003 June; 73(6): 538-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12811363

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Gender differences in blood thrombogenicity in hyperlipidemic patients and response to pravastatin. Author(s): Dangas G, Smith DA, Badimon JJ, Unger AH, Shao JH, Meraj P, Cohen AM, Levine D, Fallon JT, Ambrose JA. Source: The American Journal of Cardiology. 1999 September 15; 84(6): 639-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10498131

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Grapefruit juice increases serum concentrations of atorvastatin and has no effect on pravastatin. Author(s): Lilja JJ, Kivisto KT, Neuvonen PJ. Source: Clinical Pharmacology and Therapeutics. 1999 August; 66(2): 118-27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10460065

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Guidelines for lowering lipids to reduce coronary artery disease risk: a comparison of rosuvastatin with atorvastatin, pravastatin, and simvastatin for achieving lipidlowering goals. Author(s): Shepherd J, Hunninghake DB, Barter P, McKenney JM, Hutchinson HG. Source: The American Journal of Cardiology. 2003 March 6; 91(5A): 11C-17C; Discussion 17C-19C. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12646338

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Health-related quality of life and long-term therapy with pravastatin and tocopherol (vitamin E) in older adults. Author(s): Carlsson CM, Papcke-Benson K, Carnes M, McBride PE, Stein JH. Source: Drugs & Aging. 2002; 19(10): 793-805. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12390056

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Hemodynamic changes associated with reduction in total cholesterol by treatment with the HMG-CoA reductase inhibitor pravastatin. Author(s): Muramatsu J, Kobayashi A, Hasegawa N, Yokouchi S. Source: Atherosclerosis. 1997 April; 130(1-2): 179-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9126662

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Hemorheology and tissue oxygenation in hypertensives with lipoidoproteinosis and peripheral occlusive arterial disease (POAD) treated with sulodexide and pravastatine and evaluated with laser assisted optical rotational red cell analyzer (LORCA) and transcutaneous oxymetry. Author(s): Cicco G, Stingi GD, Vicenti P, Tarallo MS, Pirrelli A. Source: Minerva Cardioangiol. 1999 October; 47(10): 351-9. Review. English, Italian. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10670256

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High-performance liquid chromatography coupled with negative ion tandem mass spectrometry for determination of pravastatin in human plasma. Author(s): Zhu Z, Neirinck L. Source: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences. 2003 January 5; 783(1): 133-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12450532

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High-performance liquid chromatography determination of pravastatin in plasma. Author(s): Iacona I, Regazzi MB, Buggia I, Villani P, Fiorito V, Molinaro M, Guarnone E. Source: Therapeutic Drug Monitoring. 1994 April; 16(2): 191-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8009569

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HMG CoA reductase inhibitors as lipid-lowering agents: five years experience with lovastatin and an appraisal of simvastatin and pravastatin. Author(s): Maher VM, Thompson GR. Source: The Quarterly Journal of Medicine. 1990 February; 74(274): 165-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2111917

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HMG-CoA reductase inhibitors pravastatin and simvastatin inhibit human Blymphocyte activation. Author(s): Rudich SM, Mongini PK, Perez RV, Katznelson S. Source: Transplantation Proceedings. 1998 June; 30(4): 992-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9636401

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Human liver-specific organic anion transporter, LST-1, mediates uptake of pravastatin by human hepatocytes. Author(s): Nakai D, Nakagomi R, Furuta Y, Tokui T, Abe T, Ikeda T, Nishimura K. Source: The Journal of Pharmacology and Experimental Therapeutics. 2001 June; 297(3): 861-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11356905

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Hypercholesterolaemia: simvastatin and pravastatin alter cholesterol metabolism by different mechanisms. Author(s): Owens D, Collins P, Johnson A, Tighe O, Robinson K, Tomkin GH. Source: Biochimica Et Biophysica Acta. 1991 April 3; 1082(3): 303-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1903069

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Hypercoagulable state in patients with hypercholesterolemia: effects of pravastatin. Author(s): Wada H, Mori Y, Kaneko T, Wakita Y, Minamikawa K, Ohiwa M, Tamaki S, Yokoyama N, Kobayashi T, Deguchi K, et al. Source: Clinical Therapeutics. 1992 November-December; 14(6): 829-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1286491

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Hyperlipidemia after liver transplantation: natural history and treatment with the hydroxy-methylglutaryl-coenzyme A reductase inhibitor pravastatin. Author(s): Imagawa DK, Dawson S 3rd, Holt CD, Kirk PS, Kaldas FM, Shackleton CR, Seu P, Rudich SM, Kinkhabwala MM, Martin P, Goldstein LI, Murray NG, Terasaki PI, Busuttil RW. Source: Transplantation. 1996 October 15; 62(7): 934-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8878387

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Hypocholesterolemic effect of pravastatin is associated with increased content of antioxidant vitamin-E in cholesterol fractions. Author(s): Blaha V, Zadak Z, Solichova D, Bratova M, Havel E. Source: Acta Medica (Hradec Kralove). 1998; 41(2): 87-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9729642

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Impact of therapeutic interchange from pravastatin to lovastatin in a Veterans Affairs Medical Center. Author(s): Patel RJ, Gray DR, Pierce R, Jafari M. Source: Am J Manag Care. 1999 April; 5(4): 465-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10387386

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Improvement of erythrocyte deformability by cholesterol-lowering therapy with pravastatin in hypercholesterolemic patients. Author(s): Kohno M, Murakawa K, Yasunari K, Yokokawa K, Horio T, Kano H, Minami M, Yoshikawa J. Source: Metabolism: Clinical and Experimental. 1997 March; 46(3): 287-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9054471

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Improvement of serum oxidation by pravastatin might be one of the mechanisms by which endothelial function in dilated coronary artery segments is ameliorated. Author(s): Mulder HJ, Schalij MJ, van der Laarse A, Hollaar L, Zwinderman AH, Bruschke AV. Source: Atherosclerosis. 2003 August; 169(2): 309-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12921983

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Increase or decrease of HDL-cholesterol concentrations during pravastatin treatment depending on the pre-treatment HDL cholesterol levels. Author(s): Narita Y, Kitazoe Y, Kurihara Y, Okuhara Y, Takamatsu K, Saito N, Doi Y. Source: European Journal of Clinical Pharmacology. 1997; 52(6): 461-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9342581

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Increased levels of asymmetric dimethylarginine in populations at risk for atherosclerotic disease. Effects of pravastatin. Author(s): Eid HM, Eritsland J, Larsen J, Arnesen H, Seljeflot I. Source: Atherosclerosis. 2003 February; 166(2): 279-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12535740

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Increased transforming growth factor-beta(1) circulating levels and production in human monocytes after 3-hydroxy-3-methyl-glutaryl-coenzyme a reductase inhibition with pravastatin. Author(s): Porreca E, Di Febbo C, Baccante G, Di Nisio M, Cuccurullo F. Source: Journal of the American College of Cardiology. 2002 June 5; 39(11): 1752-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12039487

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Individual difference in the pharmacokinetics of a drug, pravastatin, in healthy subjects. Author(s): Ogawa K, Hasegawa S, Udaka Y, Nara K, Iwai S, Oguchi K. Source: Journal of Clinical Pharmacology. 2003 November; 43(11): 1268-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14551181

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Inflammation, pravastatin, and the risk of coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events (CARE) Investigators. Author(s): Ridker PM, Rifai N, Pfeffer MA, Sacks FM, Moye LA, Goldman S, Flaker GC, Braunwald E. Source: Circulation. 1998 September 1; 98(9): 839-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9738637

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Influence of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, pravastatin, on corticosteroid metabolism in patients with heterozygous familial hypercholesterolemia. Author(s): Takeda Y, Miyamori I, Karayalcin U, Takeda R. Source: Hormone Research. 1991; 36(1-2): 75-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1814804

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Influence of baseline lipids on effectiveness of pravastatin in the CARE Trial. Cholesterol And Recurrent Events. Author(s): Pfeffer MA, Sacks FM, Moye LA, East C, Goldman S, Nash DT, Rouleau JR, Rouleau JL, Sussex BA, Theroux P, Vanden Belt RJ, Braunwald E. Source: Journal of the American College of Cardiology. 1999 January; 33(1): 125-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9935018

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Influence of pravastatin on hepatic metabolism of cholesterol. Author(s): Hellerstein M. Source: The New England Journal of Medicine. 1991 January 10; 324(2): 128. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1898532

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Influence of pravastatin on lipoproteins, and on endothelial, platelet, and inflammatory markers in subjects with peripheral artery disease. Author(s): Blann AD, Gurney D, Hughes E, Buggins P, Silverman SH, Lip GY. Source: The American Journal of Cardiology. 2001 July 1; 88(1): A7-8, 89-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11423069

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Influence of pravastatin, a specific inhibitor of HMG-CoA reductase, on hepatic metabolism of cholesterol. Author(s): Reihner E, Rudling M, Stahlberg D, Berglund L, Ewerth S, Bjorkhem I, Einarsson K, Angelin B. Source: The New England Journal of Medicine. 1990 July 26; 323(4): 224-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2114543

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Inhibition of platelet aggregation and expression of alpha granule membrane protein 140 and thromboxane B2 with pravastatin therapy for hypercholesterolemia. Author(s): Ma LP, Nie DN, Hsu SX, Yin SM, Xu LZ, Nunes JV. Source: J Assoc Acad Minor Phys. 2002 January; 13(1): 23-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11852667

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Inhibition of proinflammatory cytokine production by pravastatin. Author(s): Rosenson RS, Tangney CC, Casey LC. Source: Lancet. 1999 March 20; 353(9157): 983-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10459915

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International economic analysis of primary prevention of cardiovascular disease with pravastatin in WOSCOPS. West of Scotland Coronary Prevention Study. Author(s): Caro J, Klittich W, McGuire A, Ford I, Pettitt D, Norrie J, Shepherd J. Source: European Heart Journal. 1999 February; 20(4): 263-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10099920

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Intima-media thickness after pravastatin stabilizes also in patients with moderate to no reduction in LDL-cholesterol levels: the carotid atherosclerosis Italian ultrasound study. Author(s): Baldassarre D, Veglia F, Gobbi C, Gallus G, Ventura A, Crepaldi G, Fisicaro M, Rimondi S, Ricci G, Mancini M, Bong MG, Collatina S, Sirtori CR. Source: Atherosclerosis. 2000 August; 151(2): 575-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10924737

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Intraoperative rhabdomyolysis in a patient receiving pravastatin, a 3-hydroxy-3methylglutaryl coenzyme A (HMG CoA) reductase inhibitor. Author(s): Rosenberg AD, Neuwirth MG, Kagen LJ, Singh K, Fischer HD, Bernstein RL. Source: Anesthesia and Analgesia. 1995 November; 81(5): 1089-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7486053

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Intravascular ultrasound analysis of reduction in progression of coronary narrowing by treatment with pravastatin. Author(s): Takagi T, Yoshida K, Akasaka T, Hozumi T, Morioka S, Yoshikawa J. Source: The American Journal of Cardiology. 1997 June 15; 79(12): 1673-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9202362

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In-vitro effect of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors on non-hepatic LDL receptor activity: evidence of lack of stimulatory effect of pravastatin. Author(s): Pedreno J, Sanchez JL, Zambon D, Ros E. Source: Coronary Artery Disease. 1994 December; 5(12): 971-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7728297

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Itraconazole alters the pharmacokinetics of atorvastatin to a greater extent than either cerivastatin or pravastatin. Author(s): Mazzu AL, Lasseter KC, Shamblen EC, Agarwal V, Lettieri J, Sundaresen P. Source: Clinical Pharmacology and Therapeutics. 2000 October; 68(4): 391-400. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11061579

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Lack of a clinically significant pharmacokinetic interaction between fenofibrate and pravastatin in healthy volunteers. Author(s): Pan WJ, Gustavson LE, Achari R, Rieser MJ, Ye X, Gutterman C, Wallin BA. Source: Journal of Clinical Pharmacology. 2000 March; 40(3): 316-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10709162

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Lack of hypotension with lovastatin and pravastatin. Author(s): Kostis JB, Wilson AC. Source: Lancet. 1991 November 23; 338(8778): 1339. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1682723

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Lipid and apolipoprotein ratios: association with coronary artery disease and effects of rosuvastatin compared with atorvastatin, pravastatin, and simvastatin. Author(s): Rader DJ, Davidson MH, Caplan RJ, Pears JS. Source: The American Journal of Cardiology. 2003 March 6; 91(5A): 20C-23C; Discussion 23C-24C. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12646340

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Lipid lowering by pravastatin increases parasympathetic modulation of heart rate: Galpha(i2), a possible molecular marker for parasympathetic responsiveness. Author(s): Welzig CM, Shin DG, Park HJ, Kim YJ, Saul JP, Galper JB. Source: Circulation. 2003 December 2; 108(22): 2743-6. Epub 2003 November 17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14623802

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Lipid-lowering diets in patients taking pravastatin, a new HMG-CoA reductase inhibitor: compliance and adequacy. Author(s): Dobs AS, Sarma PS, Wilder L. Source: The American Journal of Clinical Nutrition. 1991 October; 54(4): 696-700. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1910254

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Long-term administration of pravastatin reduces serum lipoprotein(a) levels. Author(s): Horimoto M, Hasegawa A, Takenaka T, Fujiwara M, Inoue H, Igarashi K. Source: Int J Clin Pharmacol Ther. 2003 November; 41(11): 524-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14620949

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Long-term assessment of psychological well-being in a randomized placebocontrolled trial of cholesterol reduction with pravastatin. The LIPID Study Investigators. Author(s): Stewart RA, Sharples KJ, North FM, Menkes DB, Baker J, Simes J. Source: Archives of Internal Medicine. 2000 November 13; 160(20): 3144-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11074745

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Long-term effectiveness and safety of pravastatin in 9014 patients with coronary heart disease and average cholesterol concentrations: the LIPID trial follow-up. Author(s): LIPID Study Group (Long-term Intervention with Pravastatin in Ischaemic Disease). Source: Lancet. 2002 April 20; 359(9315): 1379-87. Erratum In: Lancet 2002 November 2; 360(9343): 1430. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11978335

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Long-term effects of pravastatin on plasma concentration of C-reactive protein. The Cholesterol and Recurrent Events (CARE) Investigators. Author(s): Ridker PM, Rifai N, Pfeffer MA, Sacks F, Braunwald E. Source: Circulation. 1999 July 20; 100(3): 230-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10411845

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Long-term effects of pravastatin on serum lipid levels in elderly patients with hypercholesterolemia. Author(s): Morimoto S, Koh E, Fukuo K, Higaki J, Ikegami H, Miki T, Hata T, Ogihara T. Source: Clinical Therapeutics. 1994 September-October; 16(5): 793-803. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7859238

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Long-term efficacy and tolerability of pravastatin in hypercholesterolemia in patients with non-insulin-dependent diabetes mellitus. Hyogo Pravastatin Study Group. Author(s): Kazumi T, Yoshino G, Ishida Y, Iwatani I, Morita S, Tateiwa M, Kasuga M. Source: Diabetes Research and Clinical Practice. 1995 January; 27(1): 61-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7781495

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Long-term endocrine function in hypercholesterolemic patients treated with pravastatin, a new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor. Author(s): Dobs AS, Sarma PS, Schteingart D. Source: Metabolism: Clinical and Experimental. 1993 September; 42(9): 1146-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8412767

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Long-term experience with pravastatin in clinical research trials. Author(s): McGovern ME, Mellies MJ. Source: Clinical Therapeutics. 1993 January-February; 15(1): 57-64. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8458055

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Long-term risk stratification for survivors of acute coronary syndromes. Results from the Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) Study. LIPID Study Investigators. Author(s): Marschner IC, Colquhoun D, Simes RJ, Glasziou P, Harris P, Singh BB, Friedlander D, White H, Thompson P, Tonkin A; Long-Term Intervention with Pravastatin in Ischemic Disease (LIPID) Study. Source: Journal of the American College of Cardiology. 2001 July; 38(1): 56-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11451296

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Long-term safety of pravastatin-gemfibrozil therapy in mixed hyperlipidemia. Author(s): Iliadis EA, Rosenson RS. Source: Clin Cardiol. 1999 January; 22(1): 25-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9929751

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Long-term treatment (2 years) with the HMG CoA reductase inhibitors lovastatin or pravastatin in combination with cholestyramine in patients with severe primary hypercholesterolemia. Author(s): Jacob BG, Richter WO, Schwandt P. Source: Journal of Cardiovascular Pharmacology. 1993 September; 22(3): 396-400. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7504129

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Long-term treatment of hypercholesterolemic non-insulin dependent diabetics (NIDDM) with pravastatin (CS-514). Author(s): Yoshino G, Kazumi T, Iwai M, Matsushita M, Matsuba K, Uenoyama R, Iwatani I, Baba S. Source: Atherosclerosis. 1989 January; 75(1): 67-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2495012

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Lovastatin in pravastatin comparative trial: cost-effectiveness. Author(s): Farbstein S. Source: The American Journal of Cardiology. 1994 February 15; 73(5): 417-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8179675

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Lovastatin versus pravastatin for hypercholesterolemia. Author(s): Goldstein MR. Source: The American Journal of Cardiology. 1994 February 15; 73(5): 416; Author Reply 417-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8109563

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Lovastatin, pravastatin, and serum lipoprotein(a) Author(s): Jacob BG, Richter WO, Schwandt P. Source: Annals of Internal Medicine. 1990 May 1; 112(9): 713-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2139768

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Pravastatin

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Low-density lipoprotein receptor genotype-dependent response to cholesterol lowering by combined pravastatin and cholestyramine in familial hypercholesterolemia. Author(s): Kajinami K, Yagi K, Higashikata T, Inazu A, Koizumi J, Mabuchi H. Source: The American Journal of Cardiology. 1998 July 1; 82(1): 113-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9671018

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Low-density lipoprotein size, pravastatin treatment, and coronary events. Author(s): Campos H, Moye LA, Glasser SP, Stampfer MJ, Sacks FM. Source: Jama : the Journal of the American Medical Association. 2001 September 26; 286(12): 1468-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11572739

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Maintenance of low-density lipoprotein goal with step-down pravastatin therapy. Author(s): Graham MR, Lindsey CC, Kennedy JA. Source: Pharmacotherapy. 2002 January; 22(1): 21-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11794427

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Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs usual care: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT). Author(s): ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. Source: Jama : the Journal of the American Medical Association. 2002 December 18; 288(23): 2998-3007. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12479764

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Management of the Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) study after the Scandinavian Simvastatin Survival Study (4S). Author(s): Tonkin AM. Source: The American Journal of Cardiology. 1995 September 28; 76(9): 107C-112C. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7572678

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Marked decrease in serum HDL cholesterol levels by combined probucol-pravastatin treatment in hypercholesterolemic NIDDM patients. Author(s): Ikeda T. Source: Diabetes Care. 1993 May; 16(5): 849-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8495635

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Menopause and hyperlipidemia: pravastatin lowers lipid levels without decreasing endogenous estrogens. Author(s): Honjo H, Tanaka K, Urabe M, Naitoh K, Ogino Y, Yamamoto T, Okada H. Source: Clinical Therapeutics. 1992 September-October; 14(5): 699-707. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1345259

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Mevalonate-dependent inhibition of transendothelial migration and chemotaxis of human peripheral blood neutrophils by pravastatin. Author(s): Dunzendorfer S, Rothbucher D, Schratzberger P, Reinisch N, Kahler CM, Wiedermann CJ. Source: Circulation Research. 1997 December; 81(6): 963-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9400376

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Mibefradil, a potent CYP3A inhibitor, does not alter pravastatin pharmacokinetics. Author(s): Becquemont L, Funck-Brentano C, Jaillon P. Source: Fundamental & Clinical Pharmacology. 1999; 13(2): 232-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10226769

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Mitochondrial myopathy developing on treatment with the HMG CoA reductase inhibitors--simvastatin and pravastatin. Author(s): England JD, Walsh JC, Stewart P, Boyd I, Rohan A, Halmagyi GM. Source: Aust N Z J Med. 1995 August; 25(4): 374-5. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8540887

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Modulation of inflammatory mediators and PPARgamma and NFkappaB expression by pravastatin in response to lipoproteins in human monocytes in vitro. Author(s): Zelvyte I, Dominaitiene R, Crisby M, Janciauskiene S. Source: Pharmacological Research : the Official Journal of the Italian Pharmacological Society. 2002 February; 45(2): 147-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11846628

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Modulation of the mevalonate pathway and cell growth by pravastatin and dlimonene in a human hepatoma cell line (Hep G2). Author(s): Kawata S, Nagase T, Yamasaki E, Ishiguro H, Matsuzawa Y. Source: British Journal of Cancer. 1994 June; 69(6): 1015-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8198962

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Myotonia associated with sarcoidosis: marked exacerbation with pravastatin. Author(s): Riggs JE, Schochet SS Jr. Source: Clinical Neuropharmacology. 1999 May-June; 22(3): 180-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10367184

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Pravastatin

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No primary prevention by pravastatin. Author(s): Meyer FP. Source: The American Journal of Medicine. 1998 February; 104(2): 212-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9528746

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Non lipid, dose-dependent effects of pravastatin treatment on hemostatic system and inflammatory response. Author(s): Di Garbo V, Bono M, Di Raimondo D, De Simone R, Raneli G, Avellone G. Source: European Journal of Clinical Pharmacology. 2000 July; 56(4): 277-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10954339

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Ocular drug-safety study with the HMG-CoA reductase inhibitor pravastatin. Author(s): Schmitt C, Schmidt J, Hockwin O. Source: Lens Eye Toxic Res. 1990; 7(3-4): 631-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2129220

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Once-daily pravastatin in patients with primary hypercholesterolemia: a doseresponse study. Author(s): Jones PH, Farmer JA, Cressman MD, McKenney JM, Wright JT, Proctor JD, Berkson DM, Farnham DJ, Wolfson PM, Colfer HT, et al. Source: Clin Cardiol. 1991 February; 14(2): 146-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1904333

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Opposite effects on serum cholesteryl ester transfer protein levels between long-term treatments with pravastatin and probucol in patients with primary hypercholesterolemia and xanthoma. Author(s): Inazu A, Koizumi J, Kajinami K, Kiyohar T, Chichibu K, Mabuchi H. Source: Atherosclerosis. 1999 August; 145(2): 405-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10488970

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Oxysterol-induced apoptosis of vascular smooth muscle cells is reduced by HMGCoA reductase inhibitor, pravastatin. Author(s): Miyashita Y, Ozaki H, Koide N, Otsuka M, Oyama T, Itoh Y, Mastuzaka T, Shirai K. Source: J Atheroscler Thromb. 2002; 9(1): 65-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12238640

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Pharmacokinetic interaction between propranolol and the HMG-CoA reductase inhibitors pravastatin and lovastatin. Author(s): Pan HY, Triscari J, DeVault AR, Smith SA, Wang-Iverson D, Swanson BN, Willard DA. Source: British Journal of Clinical Pharmacology. 1991 June; 31(6): 665-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1907839

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Pharmacokinetics and pharmacodynamics of pravastatin in children with familial hypercholesterolemia. Author(s): Hedman M, Neuvonen PJ, Neuvonen M, Antikainen M. Source: Clinical Pharmacology and Therapeutics. 2003 August; 74(2): 178-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12891228

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Pharmacokinetics and pharmacodynamics of pravastatin in pediatric and adolescent cardiac transplant recipients on a regimen of triple immunosuppression. Author(s): Hedman M, Neuvonen PJ, Neuvonen M, Holmberg C, Antikainen M. Source: Clinical Pharmacology and Therapeutics. 2004 January; 75(1): 101-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14749696

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Pharmacokinetics of pravastatin in heart-transplant patients taking cyclosporin A. Author(s): Park JW, Siekmeier R, Merz M, Krell B, Harder S, Marz W, Seidel D, Schuler S, Gross W. Source: Int J Clin Pharmacol Ther. 2002 October; 40(10): 439-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12395976

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Pilot study describing the use of pravastatin in pediatric renal transplant recipients. Author(s): Butani L, Pai MV, Makker SP. Source: Pediatric Transplantation. 2003 June; 7(3): 179-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12756041

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Polymorphisms of OATP-C (SLC21A6) and OAT3 (SLC22A8) genes: consequences for pravastatin pharmacokinetics. Author(s): Nishizato Y, Ieiri I, Suzuki H, Kimura M, Kawabata K, Hirota T, Takane H, Irie S, Kusuhara H, Urasaki Y, Urae A, Higuchi S, Otsubo K, Sugiyama Y. Source: Clinical Pharmacology and Therapeutics. 2003 June; 73(6): 554-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12811365

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Pravastatin and Aspirin. Author(s): Armstrong PW, Lorell BH, Nissen S, Borer J. Source: Circulation. 2002 August 6; 106(6): E9011-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12187915

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Pravastatin and lovastatin similarly reduce serum cholesterol and its precursor levels in familial hypercholesterolaemia. Author(s): Vanhanen H, Miettinen TA. Source: European Journal of Clinical Pharmacology. 1992; 42(2): 127-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1618241

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Pravastatin at 10 mg/day does not decrease plasma levels of either amyloid-beta (Abeta) 40 or Abeta 42 in humans. Author(s): Ishii K, Tokuda T, Matsushima T, Miya F, Shoji S, Ikeda S, Tamaoka A. Source: Neuroscience Letters. 2003 October 30; 350(3): 161-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14550919

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Pravastatin does not alter protease inhibitor exposure or virologic efficacy during a 24-week period of therapy. Author(s): Moyle GJ, Buss NE, Gazzard BG. Source: Journal of Acquired Immune Deficiency Syndromes (1999). 2002 August 1; 30(4): 460-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12138355

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Pravastatin for secondary prevention of cardiovascular events in persons with mild chronic renal insufficiency. Author(s): Tonelli M, Moye L, Sacks FM, Kiberd B, Curhan G; Cholesterol and Recurrent Events (CARE) Trial Investigators. Source: Annals of Internal Medicine. 2003 January 21; 138(2): 98-104. Summary for Patients In: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12529091

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Pravastatin improves low-density lipoprotein oxidation in renal transplantation. Author(s): Cofan F, Zambon D, Laguna JC, Casals E, Ros E, Cofan M, Campistol JM, Oppenheimer F. Source: Transplantation Proceedings. 2002 February; 34(1): 389-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11959339

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Pravastatin in diabetes-associated hypercholesterolemia. Author(s): Rustemeijer C, Schouten JA, Janssens EN, Spooren PF, van Doormaal JJ. Source: Acta Diabetologica. 1997 December; 34(4): 294-300. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9451475

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Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Author(s): Shepherd J, Blauw GJ, Murphy MB, Bollen EL, Buckley BM, Cobbe SM, Ford I, Gaw A, Hyland M, Jukema JW, Kamper AM, Macfarlane PW, Meinders AE, Norrie J, Packard CJ, Perry IJ, Stott DJ, Sweeney BJ, Twomey C, Westendorp RG; PROSPER study group. PROspective Study of Pravastatin in the Elderly at Risk. Source: Lancet. 2002 November 23; 360(9346): 1623-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12457784

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Pravastatin in heterozygous familial hypercholesterolemia: low-density lipoprotein (LDL) cholesterol-lowering effect and LDL receptor activity on skin fibroblastS. Author(s): Gaddi A, Arca M, Ciarrocchi A, Fazio S, D'Alo G, Tiozzo R, Descovich GC, Calandra S. Source: Metabolism: Clinical and Experimental. 1991 October; 40(10): 1074-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1658544

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Pravastatin in hyperlipidemia secondary to HIV protease inhibitors without response to fenofibrate: a brief preliminary report. Author(s): de Luis DA, Bachiller P, Aller R, Eiros Bouza J, Izaola O. Source: Nutrition (Burbank, Los Angeles County, Calif.). 2003 October; 19(10): 903-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14559329

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Pravastatin inhibits pro-inflammatory effects of Alzheimer's peptide Abeta(1-42) in glioma cell culture in vitro. Author(s): Sun YX, Crisby M, Lindgren S, Janciauskiene S. Source: Pharmacological Research : the Official Journal of the Italian Pharmacological Society. 2003 February; 47(2): 119-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12543059

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Pravastatin promotes coronary collateral circulation in patients with coronary artery disease. Author(s): Nishikawa H, Miura S, Zhang B, Shimomura H, Arai H, Tsuchiya Y, Saku K. Source: Coronary Artery Disease. 2002 November; 13(7): 377-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12488647

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Pravastatin reduces restenosis two years after percutaneous transluminal coronary angioplasty (REGRESS trial). Author(s): Mulder HJ, Bal ET, Jukema JW, Zwinderman AH, Schalij MJ, van Boven AJ, Bruschke AV. Source: The American Journal of Cardiology. 2000 October 1; 86(7): 742-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11018193

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Pravastatin reduces the incidence of cardiac events among patients with myocardial infarction. Author(s): Furuta H, Kimura A, Miyataka M, Taniguchi M, Katayama K, Yamamoto T, Takenaka T, Hayashi T, Kanamasa K, Ishikawa K. Source: Japanese Heart Journal. 2003 November; 44(6): 873-87. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14711183

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Pravastatin sodium, a new HMG-CoA reductase inhibitor. Author(s): Raasch RH. Source: Dicp. 1991 April; 25(4): 388-94. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1926908

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Pravastatin treatment of very low density, intermediate density and low density lipoproteins in hypercholesterolemia and combined hyperlipidemia secondary to the nephrotic syndrome. Author(s): Toto RD, Grundy SM, Vega GL. Source: American Journal of Nephrology. 2000 January-February; 20(1): 12-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10644862

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Pravastatin treatment-associated reduction in plasma homocysteine in hearttransplanted patients. Author(s): Capecchi PL, Lazzerini PE, Maccherini M, Guideri F, Lisi G, Acampa M, Cuomo A, Diciolla F, Toscano M, Laghi Pasini F. Source: Transplantation Proceedings. 2002 June; 34(4): 1273-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12072338

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Pravastatin up-regulates transforming growth factor-beta1 in THP-1 human macrophages: effect on scavenger receptor class A expression. Author(s): Baccante G, Mincione G, Di Marcantonio MC, Piccirelli A, Cuccurullo F, Porreca E. Source: Biochemical and Biophysical Research Communications. 2004 February 13; 314(3): 704-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14741692

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Pravastatin, blood pressure, and stroke. Author(s): Wilkinson IB, Cockcroft JR. Source: Hypertension. 2000 September; 36(3): E1-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10988283

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Pravastatin. A review of its pharmacological properties and therapeutic potential in hypercholesterolaemia. Author(s): McTavish D, Sorkin EM. Source: Drugs. 1991 July; 42(1): 65-89. Review. Erratum In: Drugs 1991 December; 42(6): 944. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1718686

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Pravastatin-induced lichenoid drug eruption. Author(s): Keough GC, Richardson TT, Grabski WJ. Source: Cutis; Cutaneous Medicine for the Practitioner. 1998 February; 61(2): 98-100. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9515217

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Preventing angiographic progression of coronary atherosclerosis with pravastatin. Author(s): Daida H, Ouchi Y, Saito Y, Yamada N, Nishide T, Mokuno H, Kurata T, Sato H, Eto M, Ako JY, Tango T, Yamaguchi H; Coronary Atherosclerosis and Lipid Research Group. Source: J Atheroscler Thromb. 2003; 10(1): 25-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12621161

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Prognosis of hypercholesterolemic patients taking pravastatin for five years: the Chiba Lipid Intervention Program (CLIP) Study. Author(s): Saito Y, Shirai K, Sasaki N, Shinomiya M, Yoshida S; Committee of the Chiba Lipid Intervention Program Study. Source: J Atheroscler Thromb. 2002; 9(2): 99-108. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12236319

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Prospective serial evaluation of myocardial perfusion and lipids during the first six months of pravastatin therapy: coronary artery disease regression single photon emission computed tomography monitoring trial. Author(s): Schwartz RG, Pearson TA, Kalaria VG, Mackin ML, Williford DJ, Awasthi A, Shah A, Rains A, Guido JJ. Source: Journal of the American College of Cardiology. 2003 August 20; 42(4): 600-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12932588

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Quantitative determination of pravastatin and its biotransformation products in human serum by turbo ion spray LC/MS/MS. Author(s): Mulvana D, Jemal M, Pulver SC. Source: Journal of Pharmaceutical and Biomedical Analysis. 2000 October; 23(5): 851-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11022911

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Randomized comparison of the efficacy and safety of cerivastatin and pravastatin in 1,030 hypercholesterolemic patients. The Cerivastatin Study Group. Author(s): Dujovne CA, Knopp R, Kwiterovich P, Hunninghake D, McBride TA, Poland M. Source: Mayo Clinic Proceedings. 2000 November; 75(11): 1124-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11075741

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Rationale, design, and baseline results of the Pravastatin-to-Simvastatin Conversion Lipid Optimization Program (PSCOP). Author(s): Ito MK, Stolley SN, Morreale AP, Lin JC, Marcus DB. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 1999 June 1; 56(11): 1107-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10385458

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Reassuring effect of pravastatin on natural killer cell activity in stable renal transplant patients. Author(s): Vaessen LM, van Miert PP, van Gelder T, Ijzermans JN, Weimar W. Source: Transplantation. 2001 April 27; 71(8): 1175-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11374422

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Reduced cholesterol esterification in CaCo-2 cells by indirect action of pravastatin. Author(s): Reimann FM, Winkelmann F, Fellermann K, Stange EF. Source: Atherosclerosis. 1996 August 23; 125(1): 63-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8831928

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Reduced levels of TNF alpha in hypercholesterolemic individuals after treatment with pravastatin for 8 weeks. Author(s): Solheim S, Seljeflot I, Arnesen H, Eritsland J, Eikvar L. Source: Atherosclerosis. 2001 August; 157(2): 411-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11472741

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Reduction in cardiovascular events during pravastatin therapy. Pooled analysis of clinical events of the Pravastatin Atherosclerosis Intervention Program. Author(s): Byington RP, Jukema JW, Salonen JT, Pitt B, Bruschke AV, Hoen H, Furberg CD, Mancini GB. Source: Circulation. 1995 November 1; 92(9): 2419-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7586340

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Reduction in coronary events during treatment with pravastatin. PLAC I and PLAC II Investigators. Pravastatin Limitation of Atherosclerosis in the Coronary Arteries. Author(s): Furberg CD, Pitt B, Byington RP, Park JS, McGovern ME. Source: The American Journal of Cardiology. 1995 September 28; 76(9): 60C-63C. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7572689

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Reduction in serum cholesterol with pravastatin improves endothelium-dependent coronary vasomotion in patients with hypercholesterolemia. Author(s): Egashira K, Hirooka Y, Kai H, Sugimachi M, Suzuki S, Inou T, Takeshita A. Source: Circulation. 1994 June; 89(6): 2519-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8205659

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Reduction of coronary events by pravastatin--is lowering low-density lipoprotein cholesterol the answer? Author(s): Halle M, Bery A, Keul J. Source: The American Journal of Cardiology. 1997 September 1; 80(5): 683. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9295011

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Reduction of intermediate density lipoprotein by pravastatin in hemo- and peritoneal dialysis patients. Author(s): Nishizawa Y, Shoji T, Emoto M, Kawasaki K, Konishi T, Tabata T, Inoue T, Morii H. Source: Clinical Nephrology. 1995 April; 43(4): 268-77. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7606882

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Reduction of LDL cholesterol by pravastatin does not influence platelet activation in patients with mild hypercholesterolaemia at risk of coronary heart disease. Author(s): Barrow SE, Stratton PD, Benjamin N, Brassfield T, Ritter JM. Source: British Journal of Clinical Pharmacology. 1991 July; 32(1): 127-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1909541

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Reduction of stroke events with pravastatin: the Prospective Pravastatin Pooling (PPP) Project. Author(s): Byington RP, Davis BR, Plehn JF, White HD, Baker J, Cobbe SM, Shepherd J. Source: Circulation. 2001 January 23; 103(3): 387-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11157690

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Reduction of stroke incidence after myocardial infarction with pravastatin: the Cholesterol and Recurrent Events (CARE) study. The Care Investigators. Author(s): Plehn JF, Davis BR, Sacks FM, Rouleau JL, Pfeffer MA, Bernstein V, Cuddy TE, Moye LA, Piller LB, Rutherford J, Simpson LM, Braunwald E. Source: Circulation. 1999 January 19; 99(2): 216-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9892586

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Reduction of transient myocardial ischemia with pravastatin in addition to the conventional treatment in patients with angina pectoris. REGRESS Study Group. Author(s): van Boven AJ, Jukema JW, Zwinderman AH, Crijns HJ, Lie KI, Bruschke AV. Source: Circulation. 1996 October 1; 94(7): 1503-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8840836

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Relations of lipoprotein subclass levels and low-density lipoprotein size to progression of coronary artery disease in the Pravastatin Limitation of Atherosclerosis in the Coronary Arteries (PLAC-I) trial. Author(s): Rosenson RS, Otvos JD, Freedman DS. Source: The American Journal of Cardiology. 2002 July 15; 90(2): 89-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12106834

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Relationship between lipid levels and clinical outcomes in the Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) Trial: to what extent is the reduction in coronary events with pravastatin explained by on-study lipid levels? Author(s): Simes RJ, Marschner IC, Hunt D, Colquhoun D, Sullivan D, Stewart RA, Hague W, Keech A, Thompson P, White H, Shaw J, Tonkin A; LIPID Study Investigators. Source: Circulation. 2002 March 12; 105(10): 1162-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11889008

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Relationship between plasma LDL concentrations during treatment with pravastatin and recurrent coronary events in the Cholesterol and Recurrent Events trial. Author(s): Sacks FM, Moye LA, Davis BR, Cole TG, Rouleau JL, Nash DT, Pfeffer MA, Braunwald E. Source: Circulation. 1998 April 21; 97(15): 1446-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9576424

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Replacing lovastatin with pravastatin: effect on serum lipids and costs. Author(s): Korman L, Borysiuk L. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 1995 May 15; 52(10): 1078-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7656097

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Results of two clinical trials on the safety and efficacy of pravastatin 80 and 160 mg per day. Author(s): Rosenson RS, Bays HE. Source: The American Journal of Cardiology. 2003 April 1; 91(7): 878-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12667578

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Rhabdomyolysis associated with pravastatin treatment for major depression. Author(s): Takei A, Chiba S. Source: Psychiatry and Clinical Neurosciences. 1999 August; 53(4): 539. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10498240

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Risk factors for non-haemorrhagic stroke in patients with coronary heart disease and the effect of lipid-modifying therapy with pravastatin. Author(s): West MJ, White HD, Simes RJ, Kirby A, Watson JD, Anderson NE, Hankey GJ, Wonders S, Hunt D, Tonkin AM. Source: Journal of Hypertension. 2002 December; 20(12): 2513-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12473877

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Role of statins in the management of dyslipidemia after cardiac transplant: randomized controlled trial comparing the efficacy and the safety of atorvastatin with pravastatin. Author(s): Magnani G, Carinci V, Magelli C, Potena L, Reggiani LB, Branzi A. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2000 July; 19(7): 710-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10930822

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Rosuvastatin demonstrates greater reduction of low-density lipoprotein cholesterol compared with pravastatin and simvastatin in hypercholesterolaemic patients: a randomized, double-blind study. Author(s): Paoletti R, Fahmy M, Mahla G, Mizan J, Southworth H. Source: Journal of Cardiovascular Risk. 2001 December; 8(6): 383-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11873095

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Safety and efficacy of pravastatin therapy for the prevention of hyperlipidemia in pediatric and adolescent cardiac transplant recipients. Author(s): Penson MG, Fricker FJ, Thompson JR, Harker K, Williams BJ, Kahler DA, Schowengerdt KO. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2001 June; 20(6): 611-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11404165

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Safety and tolerability of pravastatin in long-term clinical trials: prospective Pravastatin Pooling (PPP) Project. Author(s): Pfeffer MA, Keech A, Sacks FM, Cobbe SM, Tonkin A, Byington RP, Davis BR, Friedman CP, Braunwald E. Source: Circulation. 2002 May 21; 105(20): 2341-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12021218

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Safety of combined pravastatin-gemfibrozil therapy. Author(s): Rosenson RS, Frauenheim WA. Source: The American Journal of Cardiology. 1994 September 1; 74(5): 499-500. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8059735

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Selective inhibition of formyl-methionyl-leucyl-phenylalanine (fMLF)-dependent superoxide generation in neutrophils by pravastatin, an inhibitor of 3-hydroxy-3methylglutaryl coenzyme A (HMG-CoA) reductase. Author(s): Kanno T, Abe K, Yabuki M, Akiyama J, Yasuda T, Horton AA. Source: Biochemical Pharmacology. 1999 December 15; 58(12): 1975-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10591153

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Serum Lp(a) concentrations are unaffected by treatment with the HMG-CoA reductase inhibitor Pravastatin: results of a 2-year investigation. Author(s): Fieseler HG, Armstrong VW, Wieland E, Thiery J, Schutz E, Walli AK, Seidel D. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1991 December 31; 204(1-3): 291-300. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1840246

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Short- and long-term effects of lovastatin and pravastatin alone and in combination with cholestyramine on serum lipids, lipoproteins and apolipoproteins in primary hypercholesterolaemia. Author(s): Jacob BG, Mohrle W, Richter WO, Schwandt P. Source: European Journal of Clinical Pharmacology. 1992; 42(4): 353-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1516599

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Short term effects of pravastatin on blood pressure in hypercholesterolaemic hypertensive patients. Author(s): O'Callaghan CJ, Krum H, Conway EL, Lam W, Skiba MA, Howes LG, Louis WJ. Source: Blood Pressure. 1994 November; 3(6): 404-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7704289

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Short-term efficacy and safety of pravastatin in 72 children with familial hypercholesterolemia. Author(s): Knipscheer HC, Boelen CC, Kastelein JJ, van Diermen DE, Groenemeijer BE, van den Ende A, Buller HR, Bakker HD. Source: Pediatric Research. 1996 May; 39(5): 867-71. Erratum In: Pediatr Res 1996 December; 40(6): 866. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8726243

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Short-term pravastatin mediates growth inhibition and apoptosis, independently of Ras, via the signaling proteins p27Kip1 and P13 kinase. Author(s): Weiss RH, Ramirez A, Joo A. Source: Journal of the American Society of Nephrology : Jasn. 1999 September; 10(9): 1880-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10477139

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Short-term treatment with low-dose pravastatin attenuates oxidative susceptibility of low-density lipoprotein in hypercholesterolemic patients. Author(s): Chen MF, Hsu HC, Lee YT. Source: Cardiovascular Drugs and Therapy / Sponsored by the International Society of Cardiovascular Pharmacotherapy. 1997 December; 11(6): 787-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9512874

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Similar effects of atorvastatin, simvastatin and pravastatin on thrombogenic and inflammatory parameters in patients with hypercholesterolemia. Author(s): Joukhadar C, Klein N, Prinz M, Schrolnberger C, Vukovich T, Wolzt M, Schmetterer L, Dorner GT. Source: Thrombosis and Haemostasis. 2001 January; 85(1): 47-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11204586

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Simvastatin and pravastatin equally improve flow-mediated dilation in males with hypercholesterolemia. Author(s): Sebestjen M, Boh M, Keber I. Source: Wiener Klinische Wochenschrift. 2002 December 30; 114(23-24): 999-1003. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12635468

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Simvastatin but not pravastatin has a direct inhibitory effect on rat and human myocyte proliferation. Author(s): Corsini A, Raiteri M, Soma MR, Gabbiani G, Paoletti R. Source: Clinical Biochemistry. 1992 October; 25(5): 399-400. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1490305

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Simvastatin but not pravastatin is very susceptible to interaction with the CYP3A4 inhibitor itraconazole. Author(s): Neuvonen PJ, Kantola T, Kivisto KT. Source: Clinical Pharmacology and Therapeutics. 1998 March; 63(3): 332-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9542477

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Simvastatin versus pravastatin: efficacy and tolerability in patients with primary hypercholesterolemia. Author(s): Malini PL, Ambrosioni E, De Divitiis O, Di Somma S, Rosiello G, Trimarco B. Source: Clinical Therapeutics. 1991 July-August; 13(4): 500-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1934003

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Simvastatin, pravastatin and lovastatin: three options for lowering cholesterol. Author(s): Holdcroft C. Source: The Nurse Practitioner. 1993 May; 18(5): 56-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8355901

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Single-dose pharmacokinetics of pravastatin and metabolites in patients with renal impairment. Author(s): Halstenson CE, Triscari J, DeVault A, Shapiro B, Keane W, Pan H. Source: Journal of Clinical Pharmacology. 1992 February; 32(2): 124-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1613121

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Small intestinal metabolism of the 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor lovastatin and comparison with pravastatin. Author(s): Jacobsen W, Kirchner G, Hallensleben K, Mancinelli L, Deters M, Hackbarth I, Baner K, Benet LZ, Sewing KF, Christians U. Source: The Journal of Pharmacology and Experimental Therapeutics. 1999 October; 291(1): 131-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10490896

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Steady state serum concentrations of pravastatin and digoxin when given in combination. Author(s): Triscari J, Swanson BN, Willard DA, Cohen AI, Devault A, Pan HY. Source: British Journal of Clinical Pharmacology. 1993 September; 36(3): 263-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9114914

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Successful dissolution of cholesterol gallstone during treatment with pravastatin. Author(s): Smit JW, van Erpecum KJ, Stolk MF, Geerdink RA, Cluysenaer OJ, Erkelens DW, van Berge Henegouwen GP. Source: Gastroenterology. 1992 September; 103(3): 1068-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1499908

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Testing cognitive function in elderly populations: the PROSPER study. PROspective Study of Pravastatin in the Elderly at Risk. Author(s): Houx PJ, Shepherd J, Blauw GJ, Murphy MB, Ford I, Bollen EL, Buckley B, Stott DJ, Jukema W, Hyland M, Gaw A, Norrie J, Kamper AM, Perry IJ, MacFarlane PW, Meinders AE, Sweeney BJ, Packard CJ, Twomey C, Cobbe SM, Westendorp RG. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2002 October; 73(4): 385-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12235304

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The combination of nebivolol plus pravastatin is associated with a more beneficial metabolic profile compared to that of atenolol plus pravastatin in hypertensive patients with dyslipidemia: a pilot study. Author(s): Rizos E, Bairaktari E, Kostoula A, Hasiotis G, Achimastos A, Ganotakis E, Elisaf M, Mikhailidis DP. Source: Journal of Cardiovascular Pharmacology and Therapeutics. 2003 June; 8(2): 12734. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12808486

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The design of a prospective study of Pravastatin in the Elderly at Risk (PROSPER). PROSPER Study Group. PROspective Study of Pravastatin in the Elderly at Risk. Author(s): Shepherd J, Blauw GJ, Murphy MB, Cobbe SM, Bollen EL, Buckley BM, Ford I, Jukema JW, Hyland M, Gaw A, Lagaay AM, Perry IJ, Macfarlane PW, Meinders AE, Sweeney BJ, Packard CJ, Westendorp RG, Twomey C, Stott DJ. Source: The American Journal of Cardiology. 1999 November 15; 84(10): 1192-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10569329

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The effect of converting from pravastatin to simvastatin on the pharmacodynamics of warfarin. Author(s): Lin JC, Ito MK, Stolley SN, Morreale AP, Marcus DB. Source: Journal of Clinical Pharmacology. 1999 January; 39(1): 86-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9987704

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The effect of pravastatin and atorvastatin on coenzyme Q10. Author(s): Bleske BE, Willis RA, Anthony M, Casselberry N, Datwani M, Uhley VE, Secontine SG, Shea MJ. Source: American Heart Journal. 2001 August; 142(2): E2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11479481

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The effect of pravastatin on plasma lipoprotein and apolipoprotein levels in primary hypercholesterolemia. The Southeastern Michigan Collaborative Group. Author(s): Rubenfire M, Maciejko JJ, Blevins RD, Orringer C, Kobylak L, Rosman H. Source: Archives of Internal Medicine. 1991 November; 151(11): 2234-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1953228

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The effect of pravastatin on renal function and lipid metabolism in patients with renal dysfunction with hypertension and hyperlipidemia. Pravastatin and Renal Function Research Group. Author(s): Imai Y, Suzuki H, Saito T, Tsuji I, Abe K, Saruta T. Source: Clinical and Experimental Hypertension (New York, N.Y. : 1993). 1999 November; 21(8): 1345-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10574417

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The effects of combination therapy with niceritrol and pravastatin on hyperlipidaemia. Author(s): Kinoshita M, Mikuni Y, Kudo M, Mori M, Horie E, Teramoto T, Matsushima T. Source: J Int Med Res. 2002 May-June; 30(3): 271-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12166344

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The effects of postal and telephone reminders on compliance with pravastatin therapy in a national registry: results of the first myocardial infarction risk reduction program. Author(s): Guthrie RM. Source: Clinical Therapeutics. 2001 June; 23(6): 970-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11440296

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The effects of pravastatin on hyperlipidemia in renal transplant recipients. Author(s): Yoshimura N, Oka T, Okamoto M, Ohmori Y. Source: Transplantation. 1992 January; 53(1): 94-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1733092

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The extent of late in-stent neointima formation is modified by treatment with pravastatin: a preliminary study with intravascular ultrasound. Author(s): Prati F, Morocutti G, Bernardi G, Sommariva L, Tomai F, Pagano A, Parma A, Boccanelli A, Fioretti P. Source: Ital Heart J. 2002 August; 3(8): 455-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12407821

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The inhibitory effects of pravastatin on natural killer cell activity in vivo and on cytotoxic T lymphocyte activity in vitro. Author(s): Katznelson S, Wang XM, Chia D, Ozawa M, Zhong HP, Hirata M, Terasaki PI, Kobashigawa JA. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 1998 April; 17(4): 335-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9588577

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The interaction of diltiazem with lovastatin and pravastatin. Author(s): Azie NE, Brater DC, Becker PA, Jones DR, Hall SD. Source: Clinical Pharmacology and Therapeutics. 1998 October; 64(4): 369-77. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9797793

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The low-density lipoprotein cholesterol-lowering effect of pravastatin and factors associated with achieving targeted low-density lipoprotein levels in an AfricanAmerican population. Author(s): Chong PH, Tzallas-Pontikes PJ, Seeger JD, Stamos TD. Source: Pharmacotherapy. 2000 December; 20(12): 1454-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11130218

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The pravastatin inflammation CRP evaluation (PRINCE): rationale and design. Author(s): Albert MA, Staggers J, Chew P, Ridker PM; PRINCE Investigators. Source: American Heart Journal. 2001 June; 141(6): 893-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11376301

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The pravastatin-induced decrease of biliary cholesterol secretion is not directly related to an inhibition of cholesterol synthesis in humans. Author(s): Kallien G, Lange K, Stange EF, Scheibner J. Source: Hepatology (Baltimore, Md.). 1999 July; 30(1): 14-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10385633

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The West of Scotland coronary prevention study: economic benefit analysis of primary prevention with pravastatin. Author(s): Caro J, Klittich W, McGuire A, Ford I, Norrie J, Pettitt D, McMurray J, Shepherd J. Source: Bmj (Clinical Research Ed.). 1997 December 13; 315(7122): 1577-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9437275

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Time course of serum lipid and lipoprotein levels after coronary bypass surgery: modification by pravastatin. Author(s): Kesteloot H, Cobbaert C, Meyns B, Szecsi J, Lesaffre E, Sergeant P. Source: Acta Cardiol. 1992; 47(6): 519-28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1290313

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Treatment of familial hypercholesterolaemia. United Kingdom lipid clinics study of pravastatin and cholestyramine. Author(s): Betteridge DJ, Bhatnager D, Bing RF, Durrington PN, Evans GR, Flax H, Jay RH, Lewis-Barned N, Mann J, Matthews DR, et al. Source: Bmj (Clinical Research Ed.). 1992 May 23; 304(6838): 1335-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1611329

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CHAPTER 2. NUTRITION AND PRAVASTATIN Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and pravastatin.

Finding Nutrition Studies on Pravastatin 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 “pravastatin” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

7

Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.

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The following information is typical of that found when using the “Full IBIDS Database” to search for “pravastatin” (or a synonym): •

Cholesterol malabsorption caused by sitostanol ester feeding and neomycin in pravastatin-treated hypercholesterolaemic patients. Author(s): Second Department of Medicine, University of Helsinki, Finland. Source: Vanhanen, H Eur-J-Clin-Pharmacol. 1994; 47(2): 169-76 0031-6970

•

Clearance of chylomicron-like lipid emulsions is increased in normal rabbits but not in heterozygous Watanabe heritable hyperlipidaemic rabbits following treatment with cholestyramine or pravastatin. Author(s): Department of Physiology, University of Western Australia, Nedlands. Source: Mamo, J C Bowler, A Redgrave, T G Elsegood, C L Clin-Exp-Pharmacol-Physiol. 1994 September; 21(9): 687-94 0305-1870

•

Combination of low-dose niacin and pravastatin improves the lipid profile in diabetic patients without compromising glycemic control. Author(s): Department of Pharmacy Practice, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock 72205, USA. [email protected] Source: Gardner, S F Marx, M A White, L M Granberry, M C Skelton, D R Fonseca, V A Ann-Pharmacother. 1997 June; 31(6): 677-82 1060-0280

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Combined effects of pravastatin and probucol on high-density lipoprotein apolipoprotein A-I kinetics in cholesterol-fed rabbits. Author(s): Department of Internal Medicine, Fukuoka University School of Medicine,Japan. Source: Saku, K Liu, R Jimi, S Matsuo, K Yamamoto, K Yanagita, T Arakawa, K Jpn-CircJ. 1995 May; 59(5): 292-8 0047-1828

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Combined treatment with captopril, hydrochlorothiazide and pravastatin in dyslipidemic hypertensive patients. Author(s): Division d'Hypertension, CHUV, Lausanne, Switzerland. Source: Waeber, B Greminger, P Riesen, W Darioli, R Simeon Dubach, D Wunderlin, R Blood-Press. 1995 November; 4(6): 358-62 0803-7051

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Effect of pravastatin on newly-secreted very low density lipoprotein composition in rats. Author(s): Second Department of Internal Medicine, Kobe University School of Medicine, Japan. Source: Yoshino, G Matsushita, M Iwai, M Morita, M Matsuba, K Hirano, T Furukawa, S Kazumi, T Baba, S Horm-Metab-Res. 1991 April; 23(4): 193-5 0018-5043

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Effects of an HMG-CoA reductase inhibitor, pravastatin, and bile sequestering resin, cholestyramine, on plasma plant sterol levels in hypercholesterolemic subjects. Author(s): Third Department of Medicine, Shiga University of Medical Science, Japan. Source: Hidaka, H Kojima, H Kawabata, T Nakamura, T Konaka, K Kashiwagi, A Kikkawa, R Shigeta, Y J-Atheroscler-Thromb. 1995; 2(1): 60-5 1340-3478

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Effects of long-term pravastatin treatment on spermatogenesis and on adrenal and testicular steroidogenesis in male hypercholesterolemic patients. Author(s): Istituto di Clinica Medica I, University of Pisa, Italy. Source: Bernini, G P Brogi, G Argenio, G F Moretti, A Salvetti, A J-Endocrinol-Invest. 1998 May; 21(5): 310-7 0391-4097

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•

Effects of lovastatin and pravastatin on the survival of hamsters with inherited cardiomyopathy. Author(s): Division of Clinical Chemistry, Department of Medicine, Albert LudwigsUniversity, Freiburg, Germany. [email protected] Source: Marz, W Siekmeier, R Muller, H M Wieland, H Gross, W Olbrich, H G JCardiovasc-Pharmacol-Ther. 2000 October; 5(4): 275-9 1074-2484

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Effects of policosanol and pravastatin on lipid profile, platelet aggregation and endothelemia in older hypercholesterolemic patients. Author(s): Medical Surgical Research Center, Havana, Cuba. [email protected] Source: Castano, G Mas, R Arruzazabala, M L Noa, M Illnait, J Fernandez, J C Molina, V Menendez, A Int-J-Clin-Pharmacol-Res. 1999; 19(4): 105-16 0251-1649

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Effects of pravastatin on cholesterol metabolism in Watanabe heritable hyperlipidemic rabbits. Author(s): UMDNJ-Robert Wood Johnson Medical School, Department of Medicine, New Brunswick, New Jersey 08903-0019. Source: Amorosa, L F Rozovski, S J Ananthakrishnan, R Coly, E AlHinai, A Martucci, C Schneider, S H Shimamura, T Khachadurian, A K Jpn-Heart-J. 1992 July; 33(4): 451-63 0021-4868

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Effects of simvastatin and pravastatin on endothelium-dependent relaxation in hypercholesterolemic rabbits. Author(s): Department of Experimental Medicine/University of Campinas, Sao Paulo, Brazil. Source: Jorge, P A Ozaki, M R Metze, K Exp-Toxicol-Pathol. 1994 December; 46(6): 465-9 0940-2993

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Efficacy and safety of pravastatin in hypertensive hypercholesterolaemic patients on antihypertensive drug therapy. Author(s): Department of Pathophysiology, University of Leuven, Belgium. Source: Celis, H Lijnen, P Fagard, R Staessen, J Thijs, L Amery, A J-Hum-Hypertens. 1994 July; 8(7): 525-30 0950-9240

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Efficacy of low-dose pravastatin in patients with mild hyperlipidemia associated with type II diabetes mellitus. Author(s): Clinique d'Endocrinologie, Hotel Dieu, Nantes, France. Source: Krempf, M Berthezene, F Wemeau, J L Moinade, S Desriac, I Amelineau, E Passa, P Diabetes-Metab. 1997 April; 23(2): 131-6 1262-3636

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Improvement of endothelial function in insulin-resistant carotid arteries treated with pravastatin. Author(s): Department of Neurological Surgery, University of Virginia Health Sciences Center, Charlottesville 22908, USA. [email protected] Source: Dumont, A S Hyndman, M E Dumont, R J Fedak, P M Kassell, N F Sutherland, G R Verma, S J-Neurosurg. 2001 September; 95(3): 466-71 0022-3085

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Pravastatin and risk factor modification in patients with moderate primary hypercholesterolaemia. Author(s): Department of General Practice, University of Otago Medical School, Dunedin. Source: Morris, R Robinson, G Tilyard, M Gurr, E N-Z-Med-J. 1996 August 23; 109(1028): 319-22 0028-8446

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Pravastatin compared to bezafibrate in the treatment of dyslipidemia in insulintreated patients with type 2 diabetes mellitus. Author(s): Department of internal medicine Ziekenhuis Amstelveen, Amstelveen, The Netherlands. [email protected] Source: Rustemeijer, C Schouten, J A Voerman, H J Hensgens, H E Donker, A J Heine, R J Diabetes-Metab-Res-Revolume 2000 Mar-April; 16(2): 82-7 1520-7552

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Pravastatin has no direct effect on transmembrane cationic transport systems in human erythrocytes and platelets. Author(s): Hypertension Unit, Campus Gasthuisberg, Leuven, Belgium. Source: Lijnen, P Petrov, V Amery, A Eur-J-Clin-Pharmacol. 1994; 47(3): 281-3 0031-6970

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Pravastatin: an antithrombotic effect independent of the cholesterol-lowering effect. Author(s): Cardiovascular Institute, Mount Sinai Medical Center, Cardiovascular Research Foundation, New York, NY 10022, USA. [email protected] Source: Dangas, G Smith, D A Unger, A H Shao, J H Meraj, P Fier, C Cohen, A M Fallon, J T Badimon, J J Ambrose, J A Thromb-Haemost. 2000 May; 83(5): 688-92 0340-6245

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Rapid reversal of endothelial dysfunction in hypercholesterolaemic rabbits treated with simvastatin and pravastatin. Author(s): Department of Experimental Medicine, State University of Campinas, Brazil. Source: Jorge, P A Osaki, M R de Almeida, E Clin-Exp-Pharmacol-Physiol. 1997 December; 24(12): 948-53 0305-1870

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Results of the low-dose (20 mg) pravastatin GISSI Prevenzione trial in 4271 patients with recent myocardial infarction: do stopped trials contribute to overall knowledge? GISSI Prevenzione Investigators (Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico). Source: Anonymous Ital-Heart-J. 2000 December; 1(12): 810-20 1129-471X

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Simvastatin but not pravastatin inhibits the proliferation of rat aorta myocytes. Author(s): Institute of Pharmacological Sciences, University of Milan, Italy. Source: Corsini, A Raiteri, M Soma, M Fumagalli, R Paoletti, R Pharmacol-Res. 1991 February; 23(2): 173-80 1043-6618

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Survival and cardiovascular pathology of heterozygous Watanabe heritable hyperlipidaemic rabbits treated with pravastatin and probucol on a low-cholesterol (0.03%)-enriched diet. Author(s): Institute for Pathology, University of Hamburg, Germany. Source: Brasen, J H Harsch, M Niendorf, A Virchows-Arch. 1998 June; 432(6): 557-62 0945-6317

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The effect of pravastatin in patients with primary hyperlipidaemia. Author(s): Department of Medicine, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan. Source: Mafauzy, M Mokhtar, M Wan Mohamad, W B Musalmah, M Med-J-Malaysia. 1995 September; 50(3): 272-7 0300-5283

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The RED-LIP study--pravastatin in primary isolated hypercholesterolemia--an open, prospective, multicenter trial. Author(s): Wilhelm Auerswald Atherosclerosis Research Group, Vienna. Source: Sinzinger, H Pirich, C Wien-Klin-Wochenschr. 1994; 106(23): 721-7 0043-5325

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Therapeutic efficacy of the HMG-CoA-reductase inhibitor hyperlipoproteinaemia type II. Author(s): Medizinische Poliklinik, University of Berne, Switzerland.

pravastatin

in

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Source: Saxenhofer, H Weidmann, P Riesen, W F Beretta Piccoli, C Fragiacomo, C Wunderlin, R Noseda, G Eur-J-Clin-Pharmacol. 1990; 39(2): 101-5 0031-6970 •

Treating hypercholesterolaemia with HMG CoA reductase inhibitors: a direct comparison of simvastatin and pravastatin. Author(s): Lipid and Diabetes Research Group, Christchurch Hospital, New Zealand. Source: Lintott, C J Scott, R S Sutherland, W H Bremer, J Aust-N-Z-J-Med. 1993 August; 23(4): 381-6 0004-8291

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Treatment of patients with familial defective apolipoprotein B-100 with pravastatin and gemfibrozil: a two-period cross-over study. Author(s): Department of Internal Medicine and Cardiology A, Aarhus Amtssygehus University Hospital, Denmark. Source: Hansen, P S Meinertz, H Gerdes, L U Klausen, I C Faergeman, O Clin-Investig. 1994 December; 72(12): 1065-70 0941-0198

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

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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov

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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/

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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/

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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/

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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/

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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/

Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats

•

Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html

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•

Google: http://directory.google.com/Top/Health/Nutrition/

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Healthnotes: http://www.healthnotes.com/

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Open Directory Project: http://dmoz.org/Health/Nutrition/

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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/

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WebMDHealth: http://my.webmd.com/nutrition

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

The following is a specific Web list relating to pravastatin; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •

Vitamins Niacin Source: Integrative Medicine Communications; www.drkoop.com Vitamin A Source: Healthnotes, Inc.; www.healthnotes.com Vitamin B3 Source: Healthnotes, Inc.; www.healthnotes.com Vitamin B3 (Niacin) Source: Integrative Medicine Communications; www.drkoop.com

•

Minerals Atorvastatin Source: Healthnotes, Inc.; www.healthnotes.com Fluvastatin Source: Healthnotes, Inc.; www.healthnotes.com HMG-CoA Reductase Inhibitors (Statins) Source: Integrative Medicine Communications; www.drkoop.com Lovastatin Source: Healthnotes, Inc.; www.healthnotes.com Pravastatin Source: Healthnotes, Inc.; www.healthnotes.com Simvastatin Source: Healthnotes, Inc.; www.healthnotes.com

Nutrition

•

Food and Diet High Cholesterol Source: Healthnotes, Inc.; www.healthnotes.com

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CHAPTER 3. CLINICAL TRIALS AND PRAVASTATIN Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning pravastatin.

Recent Trials on Pravastatin The following is a list of recent trials dedicated to pravastatin.8 Further information on a trial is available at the Web site indicated. •

Effect of pravastatin on endothelial dysfunction following a single high fat meal Condition(s): Heart Diseases Study Status: This study is no longer recruiting patients. Sponsor(s): National Center for Research Resources (NCRR) Purpose - Excerpt: There is significant evidence that HMG-CoA reductase inhibitors, a commonly used class of cholesterol lowering medications, reduce the risk of death from coronary disease. Although these medicines lower cholesterol levels, other studies suggest that they have an additional effect on improving blood vessel functioning. It has also been shown that consumption of a fatty meal temporarily alters blood vessel functioning, causing endothelial dysfunction. This study will examine if pravastatin, an HMG-CoA reductase inhibitor, improves blood vessel functioning after a fatty meal. We plan on enrolling 32 subjects, aged 18-40 years, who are healthy with no history of diabetes, smoking, high blood pressure, or heart disease. These subjects will be randomly assigned to initially receive four days of pravastatin or an inactive substance, and then crossed over to the other group. Blood vessel functioning will be monitored by a technique called flow mediated vasoactivity, which uses ultrasound measurement of the forearm artery and its response to temporary occlusion. This primary measure of flow mediated vasoactivity will be done before and after consumption of a fatty meal. We hope to show that treatment with pravastatin prevents the blood vessel dysfunction known to occur after a high fat meal. Secondary outcomes will include measurement of endothelin-l, a mediator of blood vessel functioning, and assessment of changes in lipid

8

These are listed at www.ClinicalTrials.gov.

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profiles. If pravastatin does prevent endothelial dysfunction in this setting, it could lead to further studies about their use in more acute medical settings, including heart attacks or strokes. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005117 •

Safety and Effectiveness of Fenofibrate and Pravastatin in HIV-Positive Patients with Abnormal Blood Lipids Condition(s): HIV Infections; Lipodystrophy Study Status: This study is completed. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: The purpose of this study is to compare the safety and effectiveness of fenofibrate and pravastatin in treating HIV-positive patients who have abnormal levels of fat (lipids) in the blood. Increased lipids in the blood associated with HIV infection and anti-HIV drugs is a growing problem. The drugs used in this study are known to reduce certain lipids, but little is known about their safety and effectiveness. This study will see if one of the drugs is safer and more effective than the other, or if combining the drugs is the safest and most effective way to lower lipids. This study has been changed. On June 26, 2001, this study was reviewed by the Data and Safety Monitoring Board (DSMB). The DSMB is an independent board monitoring the progress of the study. The review showed that neither pravastatin nor fenofibrate alone were effective in reaching all the cholesterol and triglyceride goals. There were no safety concerns. It is not known if the combination of fenofibrate and pravastatin is effective and safe. Therefore, it is important to continue this study. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006412

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 “pravastatin” (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:

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•

For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/

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For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html

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For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/

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For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm

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For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm

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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm

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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp

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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm

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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/

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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm

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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm

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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm

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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm

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For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm

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For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials

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CHAPTER 4. PATENTS ON PRAVASTATIN 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 “pravastatin” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on pravastatin, we have not necessarily excluded nonmedical patents in this bibliography.

Patents on Pravastatin By performing a patent search focusing on pravastatin, 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.

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example of the type of information that you can expect to obtain from a patent search on pravastatin: •

Actinomycete promoter Inventor(s): Serizawa; Nobufusa (Tokyo, JP), Watanabe; Ichiro (Tokyo, JP) Assignee(s): Sankto Company, Limited (tokyo, Jp) Patent Number: 5,830,695 Date filed: November 27, 1996 Abstract: A 1 kbp length of the 5'-noncoding region of the gene encoding cytochrome P450.sub.sca-2 in the actinomycete Streptomyces carbophilus has transcription promoter activity which is substrate inducible. When the 1 kbp region is shortened, transcription activity becomes constitutive and the shortened promoters can be used advantageously in expression systems, especially those expressing P-450.sub.sca-2 in the presence of ML-236B to produce pravastatin sodium. Excerpt(s): The present invention relates to a new form of the transcription promoter associated with the gene encoding a P-450 cytochrome present in Streptomyces carbophilus, vectors containing this promoter, the use of such vectors in the expression of proteins, especially P-450.sub.sca-2, host cells containing such vectors, expression systems comprising such cells and the use of such proteins and expression systems. The present invention further allows industrial scale production of useful proteins using this promoter. In recent years, progress in the field of genetic engineering has made it readily possible to introduce and express foreign genes in various micro-organisms. A particular area of progress has been in respect of Escherichia coli (E. coli) for use as a host for the production of recombinant proteins, and the resulting techniques are being put into commercial use throughout industry. More recently, considerable progress has been made in research on yeasts as industrial alternatives to E. coli. Actinomycetes (and particularly the genus Streptomycetes) are prokaryotic micro-organisms commonly used in the production of antibiotics. Heterologous DNA is generally introduced into Actinomycetes using a host-vector system developed by Hopwood et al. in the 1980's ›c.f. Hopwood, D. A., et al., (1987), "Methods in Enzymology", 153; 116-166, Academic Press, New York!. This technique enabled considerable research and development to proceed on expression vector systems in the Actinomycetes. An example of a transcription promoter useful in Actinomycetes expression vectors is tipA, a promoter inducible by the antibiotic thiostrepton ›c.f. Murakami, T., et al., (1989), J. Bacteriol., 171, 1459!. Web site: http://www.delphion.com/details?pn=US05830695__

•

Combination of pravastatin and nicotinic acid or related acid and method for lowering serum cholesterol using such combination Inventor(s): Dennick; Leonard G. (Princeton, NJ) Assignee(s): E. R. Squibb & Sons, Inc. (princeton, Nj) Patent Number: 5,260,305 Date filed: June 18, 1992 Abstract: A pharmaceutical combination is provided which includes an inhibitor of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, which is

Patents 75

pravastatin and a pharmaceutical which reduces serum cholesterol and/or inhibits cholesterol biosynthesis by a mechanism other than inhibiting production of the enzyme HMG CoA reductase, namely, nicotinic acid (niacin) or related acid. A method for reducing serum cholesterol or inhibiting formation of or treating atherosclerosis using the above combination without causing drug-induced myopathy or rhabdomyolysis, is also provided. Excerpt(s): The present invention relates to a combination of an inhibitor of 3-hydroxy-3methylglutaryl coenzyme A (HMG CoA) reductase which is pravastatin and nicotinic acid or related acid which reduces serum cholesterol other than by inhibiting the enzyme HMG CoA reductase, and to methods for lowering serum cholesterol and triglycerides and/or preventing or treating atherosclerosis and/or elevated triglycerides by administering such combination. The above methods may be carried out without causing drug- induced myopathy or rhabdomyolysis. There are several different classes of compounds which have serum cholesterol lowering properties. Some of these compounds are inhibitors of the enzyme HMG CoA reductase which is essential in the production of cholesterol, such as mevastatin (disclosed in U.S. Pat. No. 3,983,140), lovastatin also referred to as mevinolin (disclosed in U.S. Pat. No. 4,231,938), pravastatin (disclosed in U.S. Pat No. 4,346,227) and velostatin also referred to as synvinolin (disclosed in U.S. Pat. Nos. 4,448,784 and 4,450,171). Other compounds which lower serum cholesterol may do so by an entirely different mechanism than the HMG CoA reductase inhibitors. For example, serum cholesterol may be lowered through the use of bile acid sequestrants such as cholestyramine, colestipol, DEAE-Sephadex and poly(diallylmethylamine) derivatives (such as disclosed in U.S. Pat. Nos. 4,759,923 and 4,027,009) or through the use of antihyperlipoproteinemics such as probucol and gemfibrozil which apparently lower serum lower density lipoproteins (LDL) and/or converts LDL into high density lipoproteins (HDL). Web site: http://www.delphion.com/details?pn=US05260305__ •

Enteric coated pharmaceutical compositions Inventor(s): Hodges; Garry R. (Merseyside, GB2), McCann; David L. (Merseyside, GB2) Assignee(s): E. R. Squibb & Sons, Inc. (princeton, Nj) Patent Number: 5,225,202 Date filed: September 30, 1991 Abstract: An enteric coated pharmaceutical composition is provided which includes a medicament which is sensitive to a low pH environment of less than 3, such as pravastatin, which composition is preferably in the form of pellets which includes an enteric coating formed of neutralized hydroxypropylmethyl cellulose phthalate, plasticizer and anti-adherent. The so-coated pellets have good resistance to deterioration at pH less than 3 but have good drug release properties at greater than 3. Excerpt(s): The present invention relates to an enteric coated pharmaceutical composition, preferably in the form of pellets, which includes a medicament which is sensitive to a low pH environment of less than 3, such as pravastatin, yet such composition has good protection (that is low rates of drug release) at such low pH, but has good drug release properties at pH's greater than 3. Enteric coatings have long been used to inhibit release of drug from tablets and pellets. The enteric coatings are resistant to stomach acid for required periods of time depending on the composition and/or thickness thereof, before they begin to disintegrate and allow for slow release of drug in

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the stomach and/or upper intestines. Some examples of coatings previously employed are beeswax and glyceryl monostearate; beeswax, shellac and cellulose; and cetyl alcohol, mastic and shellac as well as shellac and stearic acid (U.S. Pat. No. 2,809,918); polyvinylacetate and ethyl cellulose (U.S. Pat. No. 3,835,221); and neutral copolymer of polymethacrylic acid esters (Eudragit L30D). (F. W. Goodhart et al, Pharm. Tech., pp 6471, April, 1984); copolymers of methacrylic acid and methacrylic acid methyl ester (Eudragits), or a neutral copolymer of polymethacrylic acid esters containing metallic stearates (Mehta et al U.S. Pat. Nos. 4,728,512 and 4,794,001). Most available enteric coating polymers begin to become soluble at pH 5.5 and above, with maximum solubility rates at pH's greater than 6.5. Web site: http://www.delphion.com/details?pn=US05225202__ •

Method for lowering serum cholesterol employing a phosphorus containing ACE inhibitor alone or in combination with a cholesterol lowering drug Inventor(s): Aberg; A. K. Gunnar (Lawrenceville, NJ), Ferrer; Patricia (Pennington, NJ), Kowala; Mark (Lawrenceville, NJ) Assignee(s): E. R. Squibb & Sons, Inc. (princeton, Nj) Patent Number: 5,157,025 Date filed: April 1, 1991 Abstract: A method is provided for lowering serum cholesterol and thereby inhibiting fatty streak lesions of atherosclerosis by administering to a patient a phosphoruscontaining ACE inhibitor, such as fosinopril or ceronapril, alone or in combination with a cholesterol lowering drug, such as pravastatin. Excerpt(s): The present invention relates to a method for lowering serum cholesterol in mammalian species by administering a phosphorus-containing ACE inhibitor, such as fosinopril or ceronapril, alone or in combination with a cholesterol lowering drug, for example an HMG CoA reductase inhibitor, such as pravastatin, lovastatin or simvastatin. It has been shown that captopril, an angiotensin converting enzyme (ACE) inhibitor decreased the development of experimental atherosclerosis in monkeys fed cholesterol (Aberg, G. and Ferrer, P. "Effects of Captopril on Atherosclerosis in Cynomolgus Monkeys," J. Cardiovascular Pharmacology, 15 (suppl.5), S65-S72, 1990), and in the genetic hyperlipidemic Watanabe rabbit (Chobanian, A. V. et al, "Antiatherogenic Effect of Captopril in the Watanabe Heritable Hyperlipidemic Rabbit," Hypertension, 15, 327-331, 1990). It is also known that captopril and cilazapril retarded the proliferation of intimal smooth muscle cells after denuding the carotid artery of rats with a balloom catheter (Powell, J. S. et al, "Inhibitors of Angiotensin-Converting Enzyme Prevent Myointimal Proliferation After Vascular Injury," Science 245, 186-188, 1989). However the effect of ACE inhibitors on the initial cellular events of atherosclerosis remain unkown. In early atherosclerosis, the monocyte/macrophage is a key player. Hypercholestrolemia promotes the adhesion of blood-borne monocytes to the luminal surface of arteries, and then these leukocytes migrate into the intima. As tissue macrophages, they phagocytose modified LDL particles and transform into foam cells. Foam cells accumulate in the intima to form fatty streaks and they are also present in mature atherosclerotic plaques (Ross, R., "The Pathogenesis of Atherosclerosis--an Update," N. Engl. J. Med., 314, 488-500, 1986; Munro, J. M. and Cotran, R. S., "Biology of Disease. The Pathogenesis of Atherosclerosis: Atherogenesis and Inflammation," Lab. Invest., 58, 249-261, 1988; Steinberg, D. et al, "Beyond Cholesterol. Modifications of Low-

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Density Lipoprotein that Increases its Atherogenicity," N. Engl. J. Med., 320, 915-924, 1989). Web site: http://www.delphion.com/details?pn=US05157025__ •

Method for producing pravastatin precursor, ML-236B Inventor(s): Chung; Kae Jong (Seoul, KR), Lee; Joo Kyung (Seoul, KR), Lee; Sang Choon (Seoul, KR), Park; Joo Woong (Seoul, KR), Seo; Dong Jin (Kyungki-do, KR) Assignee(s): Yungjin Pharameutical Ind. Co., Ltd. (kr) Patent Number: 6,204,032 Date filed: December 29, 1998 Abstract: The present invention is related to a new method for producing ML-236B, a precursor of pravastatin sodium, in particular to a method for producing ML-236B lactone form(I), free acid form(II), sodium salt(III) shown in the formulae (I), (II), (III) by using a new microorganism isolated from soil. ML-236B is obtained from the culture broth of this microorganism and it is used as a substrate of pravastatin sodium which is a potent cholesterol-lowering agent used in treatment for hypercholesterolemia. Excerpt(s): It has been known that heart disease such as myocardial infarction, arteriosclerosis have been caused mainly by hyperlipidemia, especially hypercholesterolemia. It was reported by U.S. Pat. No. 3,983,140 and UK. Patent No. 1,453,425 that a cholesterol-lowering compound called ML-236B produced by a fungus Penicillium sp. had been discovered. ML-236B is produced by soil microorganisms or chemical conversion. It was reported that Penicillium brevicompactin, Penicilmyces sp., Trichoderma longibraiatum, Trichoderma pseudokoningi, Hyphomyces chrisopomus and Penicillium citrium produced ML-236B(David et al., "Biotechnology of filamentous fungi", p241; JP Publication No. Pyung 4-349034). Particularly, Sankyo Pharmaceutical Company, Japan, had developed Penicillium citrium SANK 18767 by mutation of a strain Penicillium citrium NRRL-8082 which was reported in 1971. By continuing strain development for 14 years, they had obtained Penicillium citrium Thom SANK 13380. ML-236B productivity had risen from 1.75 mg/l to 42.5 mg/l. However, the method above described required so much time about 14 years to develop a strain with high ML-236B productivity. It also needed a little long cultivation time, 14 days, and showed relatively low ML-236B productivity. Web site: http://www.delphion.com/details?pn=US06204032__

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Method for treating hypertension employing a cholesterol lowering drug Inventor(s): Bergey; James L. (Lansdale, PA), Kawano; James C. (Narberth, PA), Tschollar; Werner (Lawrenceville, NJ), Yonce; Cary S. (Newtown, PA) Assignee(s): E. R. Squibb & Sons, Inc. (princeton, Nj) Patent Number: 5,461,039 Date filed: November 1, 1993 Abstract: A method is provided for treating hypertension in normotensive patients having insulin resistance by administering a cholesterol lowering drug, such as pravastatin, alone or in combination with an ACE inhibitor, especially one containing a mercapto moiety, such as captopril or zofenopril.

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Excerpt(s): The present invention relates to a method for preventing onset of hypertension in a normotensive mammalian species with insulin resistance by administering a cholesterol-lowering drug, preferably, an HMG CoA reductase inhibitor, such as pravastatin alone or in combination with an ACE inhibitor, such as captopril or ceranapril. The role of insulin resistance and consecutive hyperinsulinemia in the pathogenesis of non-insulin dependent diabetes (NIDDM) and atherosclerosis is firmly established, Olefsky, J. M., et al, "Insulin Action and Resistance in obesity and non-insulin dependent type II diabetes mellitus," Am. J. Physiol. 1982; 243:E15-E30. Reaven, G. M., "Role of insulin resistance in human disease," Diabetes 1988; 37:15951607. Stout, R. W., "Insulin and atheroma--an update," Lancet 1987; I;1077-1079. Recently the atherogenic risk of elevated insulin concentrations in prediabetic insulin resistant states like obesity, glucose intolerance, essential hypertension and --surprisingly--in "healthy" subjects with normal oral glucose tolerance has gained increasing interest, Ferrannini, E., et al, "Insulin resistance in essential hypertension," N. Engl. J. Med. 1987; 317:350-357. Standl, E., "Hyperinsulinamie -eine Ursache der Makroangiopathie?" Akt Endokr Stoffw 1989; 10:41-46 (Sonderheft). Stout, R. W., supra, Torlone E., et al, "Effects of captopril on insulin-mediated carbohydrate and lipid metabolism in subjects with NIDDM and hypertension, "Diabetes 1989; 38(Suppl. 2):88A. Hyperinsulinemia appears to be the earliest and strongest detectable risk factor for coronary heart disease, Eschwege, E., et al, "Coronary heart disease mortality in relation with diabetes, blood glucose and plasma insulin levels. The Paris Prospective Study, ten years later," Horm. Metab. Res. Suppl. 1985; 15:41-46. Modan, M., et al, "Hyperinsulinemia--a link between glucose intolerance, obesity, hypertension, dyslipoproteinaemia, elevated serum uric acid and internal kation imbalance," Diab. Met. 1987; 13:375-380, and as a recent prospective study showed, insulin resistant hypertensive subjects have a markedly elevated risk to develop NIDDM in addition to their already high atherogenic risk, Skarfors, E. T., et al, "Do antihypertensive drugs precipitate diabetes in predisposed man?" Br. Med. J. 1989; 298:1147-1152. Pollare, T., et al, "Insulin Resistance is a Characteristic of Primary Hypertension Independent of Obesity," Metabolism, Vol. 38, No. 12 (Dec.), 1989:pp 1-9 discloses that hypertension is associated with hyperinsulinemia independently of either obesity or glucose tolerance. Web site: http://www.delphion.com/details?pn=US05461039__ •

Method for treating type II diabetes employing a cholesterol lowering drug Inventor(s): Bergman; Michael (Princeton, NJ), Pan; Henry Y. (Princeton, NJ) Assignee(s): E. R. Squibb & Sons, Inc. (princeton, Nj) Patent Number: 5,130,333 Date filed: October 19, 1990 Abstract: A method is provided for preventing or reducing the risk of or treating Type II diabetes by administering a cholesterol lowering drug, such as pravastatin, alone or in combination with an ACE inhibitor, such as captopril, zofenopril, ceranapril, fosinopril, enalapril or lisinopril. Excerpt(s): The present invention relates to a method for preventing onset of or treating non-insulin dependent diabetes, that is Type II diabetes, in mammalian species by administering a cholesterol lowering drug, such as an HMG CoA reductase inhibitor, such as pravastatin, alone or in combination with an ACE inhibitor, such as captopril, zofenopril, fosinopril or ceronapril. The use of HMG CoA reductase inhibitors in diabetics with concomitant hypercholesterolemia problems is disclosed by Yoshino G. et

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al, "Effect of CS-514, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on lipoprotein and apolipoprotein in plasma of hypercholesterolemic diabetics," Diabetes Res. Clin. Pract. (Netherlands), 1986, 2/3 (179-181). In addition, Garg and Grundy, "Lovastatin Therapy for Cholesterol Lowering in Non-Insulin Dependent Diabetes Mellitus (NIDDM)," Clin. Res. (35, No 3, 503A, 1987). Garg et al conclude that coronary risk in NIDDM should be reduced by lovastatin therapy. (2) "Treatment of dyslipidemia in non-insulin-dependent diabetes mellitus with lovastatin," Am. J. Cardiol. (US) Nov. 11, 1988, 62 (15) p. 44J-49J. Web site: http://www.delphion.com/details?pn=US05130333__ •

Method of inhibiting or treating phytosterolemia with an MTP inhibitor Inventor(s): Gregg; Richard E. (Pennington, NJ) Assignee(s): Bristol-myers Squibb Company (princeton, Nj) Patent Number: 6,057,339 Date filed: January 10, 1998 Abstract: A method is provided for inhibiting onset of or treating phytosterolemia by administering to a patient an MTP inhibitor, alone or optionally, in combination with another cholesterol lowering drug, such as pravastatin. Excerpt(s): The present invention related to a method for inhibiting onset of or treating phytosterolemia, by administering an MTP inhibitor alone or in combination with another cholesterol lowering drug, such as pravastatin. The microsomal triglyceride transfer protein (MTP) catalyzes the transport of triglyceride (TG), cholesteryl ester (CE), and phosphatidylcholine (PC) between small unilamellar vesicles (SUV). Wetterau & Zilversmit, Chem. Phys. Lipids 38, 205-22 (1985). When transfer rates are expressed as the percent of the donor lipid transferred per time, MTP expresses a distinct preference for neutral lipid transport (TG and CE), relative to phospholipid transport. The microsomal triglyceride transfer protein from bovine liver has been isolated and extensively characterized (1). This has led to the cloning of cDNA expressing the protein from several species, including humans (2). MTP is composed of two subunits. The small subunit is the previously characterized multifunctional protein, protein disulfide isomerase. This is supported by biochemical analysis of the protein (3) as well as coexpression studies performed in insect Sf9 cells using the baculovirus expression system. Expression of soluble active MTP requires the co-expression of PDI and the unique large subunit of MTP (4). 1: Wetterau, J. R. and Zilversmit, D. B. (1985) Chem. Phys. Lipids 38, 205-222. Web site: http://www.delphion.com/details?pn=US06057339__

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Method of preventing or treating statin-induced toxic effects using L-carnitine or an alkanoyl L-carnitine Inventor(s): Arduini; Arduino (Rome, IT), Carminati; Paolo (Milan, IT), Peschechera; Alessandro (Ostia Lido, IT) Assignee(s): Sigma-tau (rome, It) Patent Number: 6,245,800 Date filed: September 1, 1999

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Abstract: A pharmaceutical composition is described, comprising a lipid-lowering drug such as lovastatin, simvastatin, pravastatin and fluvastatin and L-carnitine or an alkanoyl L-carnitine, which, while conserving the efficacy of the lipid-lowering drug, is substantially devoid of the toxic or side effects typical of such drugs. Excerpt(s): The invention described herein relates to a pharmaceutical composition for the treatment of diseases caused by lipid metabolism disorders, and in particular a pharmaceutical composition comprising a statin and L-carnitine or one of its alkanoyl derivatives, useful for the prevention and treatment of statin-induced toxic or side effects. Cardiovascular diseases related to lipid metabolism disorders are very frequent in the industrialised countries. In Italy, for instance, they account for more than 40% of the overall mortality (Capocaccia R., Farchi G., Prati S. et al.: La mortalita' in Italia nell'anno 1989. Rapporto ISTISAN 1992/22). Our knowledge of the relationships between cholesterol and coronary heart disease stems from epidemiological studies conducted in recent years. The conclusions of these studies indicate that the development of severe coronary atherosclerosis is closely related to serum cholesterol levels (McGill H. C. Jr. et al.: The International Atherosclerosis Project. Lab. Invest. 18: 463-653, 1968; Keys A.: Seven Countries: Death and Coronary Heart Disease. Harvard University Press, Cambridge, 1980). Correction of eating habits through an appropriate diet is always the first measure to be adopted in cases of hyperlipidaemia. Good results, however, are not always achieved owing to widespread intolerance of the strict dietary regimen, to the severity of the hypercholesterolaemia or to genetic-type resistance. Web site: http://www.delphion.com/details?pn=US06245800__ •

Pravastatin pharmaceuatical compositions having good stability Inventor(s): Chiesa; Pierina (South Orange, NJ), Jain; Nemichand B. (Monmouth Junction, NJ), Joshi; Yatindra M. (Piscataway, NJ) Assignee(s): E. R. Squibb & Sons, Inc. (princeton, Nj) Patent Number: 5,180,589 Date filed: May 20, 1991 Abstract: A pharmaceutical composition is provided which has excellent stability, when dispersed in water has a pH of at least about 9, and includes a medicament which is sensitive to a low pH environment such as pravastatin, one or more fillers such as lactose and/or microcrystalline cellulose, one or more binders, such as microcrystalline cellulose (dry binder) or polyvinylpyrrolidone (wet binder), one or more disintegrating agents such as croscarmellose sodium, one or more lubricants such as magnesium stearate and one or more basifying agents such as magnesium oxide. Excerpt(s): The present invention relates to a pharmaceutical composition, preferably in the form of a tablet, which includes a medicament which is sensitive to a low pH environment, such as pravastatin, yet has excellent stability. Pharmaceutical compositions which include a medicament which is unstable in an acidic environment will require a basic excipient to enhance storage stability. In accordance with the present invention, a pharmaceutical composition is provided which has excellent storage stability even though it includes a medicament which may degrade in a low pH environment. The pharmaceutical composition of the invention, which is preferably in the form of a tablet, includes a medicament which is sensitive to a low pH environment, such as pravastatin, one or more fillers, such as lactose and/or microcrystalline cellulose, one or more binders, such as mirocrystalline cellulose (dry binder) or

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polyvinylpyrrolidone (wet binder), one or more disintegrating agents such as croscarmellose sodium, one or more lubricants such as magnesium stearate, and one or more basifying agents such as magnesium oxide to impart a pH to an aqueous dispersion of the composition of at least about 9.0. Web site: http://www.delphion.com/details?pn=US05180589__ •

Process for recovering statin compounds from a fermentation broth Inventor(s): Deak; Lajos (Debrecen, HU), Forgacs; Iiona (Debrecen, HU), Keri; Vilmos (Debrecen, HU), Nagyne; Edit Arvai (Debrecen, HU), Szabo; Csaba (Debrecen, HU) Assignee(s): Biogal Gyogyszergyar Rt. (hungary, Hu) Patent Number: 6,689,590 Date filed: July 23, 2002 Abstract: A composition comprising pravastatin sodium substantially free of pravastatin lactone is described. Excerpt(s): The present invention relates to methods for isolating desired chemical products of reactions conducted in aqueous fermentation broths. The invention further relates to isolation of pravastatin, compactin and lovastatin from a fermentation broth and in particular to isolation of pravastatin made by fermentation of compactin. Complications of cardiovascular disease, such as myocardial infarction, stroke, and peripheral vascular disease account for half of the deaths in the United States. A high level of low density lipoprotein (LDL) in the bloodstream has been linked to the formation of coronary lesions which obstruct the flow of blood and can rupture and promote thrombosis. Goodman and Gilman, The Pharmacological Basis of Therapeutics 879 (9th ed. 1996). Reducing plasma LDL levels has been shown to reduce the risk of clinical events in patients with cardiovascular disease and in patients who are free of cardiovascular disease but who have hypercholesterolemia. Scandinavian Simvastatin Survival Study Group, 1994; Lipid Research Clinics Program, 1984a, 1984b. Statin drugs are currently the most therapeutically effective drugs available for reducing the level of LDL in the blood stream of a patient at risk for cardiovascular disease. This class of drugs includes, inter alia, compactin, lovastatin, simvastatin, pravastatin and fluvastatin. The mechanism of action of statin drugs has been elucidated in some detail. They disrupt the synthesis of cholesterol and other sterols in the liver by competitively inhibiting the 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase enzyme ("HMG-CoA reductase"). HMG-CoA reductase catalyzes the conversion of HMG-CoA to mevalonate, which is the rate determining step in the biosynthesis of cholesterol. Consequently, its inhibition leads to a reduction in the rate of formation of cholesterol in the liver. Web site: http://www.delphion.com/details?pn=US06689590__

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Process for the preparation of simvastatin and analogs thereof Inventor(s): Zlicar; Marco (Celje, SI) Assignee(s): Lek Pharmaceutical and Chemical Company D.d. (ljubljana, Si) Patent Number: 6,384,238 Date filed: May 31, 2001

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Abstract: Lovastatin, pravastatin, simvastatin, mevastatin, derivatives and analogs thereof are known as HMG-CoA reductase inhibitors and are used as antihypercholesterolemic agents. The majority of them are produced by fermentation using microorganisms of different species identified as species belonging to Aspergillus, Monascus, Nocardia, Amycolatopsis, Mucor or Penicillium genus, and some are obtained by treating the fermentation products using the methods of chemical synthesis for example simvastatin. This invention relates to the novel method for the acylation of sterically hindered alcohols which is applicable in the process for the preparation of simvastatin and derivatives thereof. Excerpt(s): Lovastatin, pravastatin, simvastatin, mevastatin, atorvastatin, derivatives and analogs thereof are known as HMG-CoA reductase inhibitors and are used as antihypercholesterolemic agents. The majority of them are produced by fermentation using microorganisms of different species identified as species belonging to Aspergillus, Monascus, Nocardia, Amycolatopsis, Mucor or Penicillium genus, some are obtained by treating the fermentation products using the methods of chemical synthesis (simvastatin) or they are the products of total chemical synthesis. In the literature several processes for the preparation of simvastatin are known which are mainly based on one of the two following basic principles. A process of direct methylation of the 2-(S)methylbutyryloxy side chain of lovastatin is disclosed in U.S. Pat. No. 4,582,915. That process is based on direct methylation of the 2-(S)-methylbutyryloxy side chain of lovastatin using a methyl alkyl amide and a methyl halide in a single step. The described process has certain disadvantages: the low level of conversion in the Cmethylation step, low temperatures (-70 to -15.degree. C.) required for the reaction to be carried out and a number of undesired side reactions of methylation occurring at other sites of the molecule as well as using of butyl lithium which produces an explosive reaction with water and is highly pyrogen at higher concentrations. With minor modifications the yields in the methylation step may be improved, however, the total yields remain relatively low. U.S. Pat. No. 4,820,850 discloses a process for methylation of the 2-(S)-methylbutyrylox side chain of lovastatin using a single charge of amide base and alkyl halide. The process disclosed therein involves six steps; despite the fact that the level of conversion is high in the methylation step, the process is not economical. Web site: http://www.delphion.com/details?pn=US06384238__ •

Stable pharmaceutical formulation comprising a HMG-CoA reductase inhibitor Inventor(s): Kerc; Janez (Ljubljana, SI) Assignee(s): Lek Pharmaceuticals D.d. (ljubljana, Si) Patent Number: 6,680,341 Date filed: October 16, 2000 Abstract: Atorvastatin and pravastatin may be destabilized by the environmental factors, their degradation may also be accelerated by interactions with other pharmaceutical ingredients, such as fillers, binders, lubricants, glidants and disintegrating agents, therefore the pharmaceutical ingredients and the process for preparation of the pharmaceutical formulation should be meticulously chosen to avoid the aforementioned undesired interactions and reactions.The present invention relates to a stable solid pharmaceutical formulation for the treatment of hypercholesterolemia and hyperlipidemia. More precisely, the present invention relates to the new stable solid pharmaceutical formulation containing as an active ingredient, an HMG-CoA reductase

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inhibitor, such as atorvastatin and pravastatin and pharmaceutically acceptable salts thereof. Excerpt(s): The present invention relates to a new stable solid pharmaceutical formulation which is particularly suitable for the treatment of hypercholesterolemia and hyperlipidemia. More precisely, the present invention relates to the new stable solid pharmaceutical formulation containing as an active substance a HMG-CoA reductase inhibitor, such as atorvastatin, pravastatin, fluvastatin and cervastatin, or pharmaceutically active salts thereof. Lovastatin, pravastatin, simvastatin, mevastatin, atorvastatin, fluvastatin and cervastatin, derivatives and analogs thereof are known as HMG-CoA reductase inhibitors and are used as antihypercholesterolemic agents. The majority of them are produced by fermentation using microorganisms of different species identified as species belonging to Aspergillus, Monascus, Nocardia, Amycolatopsis, Mucor or Penicillium genus. Some are obtained by treating the fermentation products using the methods of chemical synthesis like simvastatin or they are the products of total chemical synthesis like fluvastatin, atorvastatin and cervastatin. The purity of the active substance is an important factor for manufacturing a safe and effective pharmaceutical formulation. Maximum possible purity of the product is of particular importance if the pharmaceutical product must be taken on a longer term basis in the treatment or prevention of high cholesterol levels in blood. Accumulation of impurities from drugs of a lower level of purity may cause a variety of side effects during treatment. Besides impurities, that cannot be completely eliminated in the process of preparation of the active substance, degradation products occurring by subjecting the final pharmaceutical formulation to various environmental factors such as temperature, moisture, low pH and light, may also impose a problem. HMG-CoA reductase inhibitors occurring in the form of salts in the final pharmaceutical formulation, such as atorvastatin, pravastatin, fluvastatin and cervastatin, are particularly sensitive to an acidic environment in which hydroxy acids are degraded into a lactone. Web site: http://www.delphion.com/details?pn=US06680341__ •

Treatment of arteriosclerosis and xanthoma Inventor(s): Horikoshi; Hiroyoshi (Kobe, JP), Ito; Takashi (Kobe, JP), Tsujita; Yoshio (Tokyo, JP) Assignee(s): Sankyo Company, Limited (tokyo, Jp) Patent Number: 5,798,375 Date filed: July 2, 1996 Abstract: A combination of one or more HMG-CoA reductase inhibitors (for example pravastatin, lovastatin, simvastatin, fluvastatin, rivastatin or atorvastatin) with one or more insulin sensitizers (for example troglitazone, pioglitazone, englitazone, BRL-49653, 5-(4-{2-›1-(4-2'-pyridylphenyl)ethylideneaminooxy!-ethoxy}benzyl)thiazolid ine-2,4dione, 5-{4-(5-methoxy-3-methylimidazo›5,4-b!pyridin-2-yl-methoxy)benzyl}thiazoli dine-2,4-dione or its hydrochloride, 5-›4-(6-methoxy-l-methylbenzimidazol-2ylmethoxy)benzyl!thiazolidine-2,4-d ione, 5-›4-(l-methylbenzimidazol-2ylmethoxy)benzyl!-thiazolidine-2,4-dione and 5-›4-(5-hydroxy-1,4,6,7tetramethylbenzimidazol-2-ylmethoxy) benzyllthiazolidine-2,4-dione) exhibits a synergistic effect and is significantly better at preventing and/or treating arteriosclerosis and/or xanthoma than is either of the components of the combination alone.

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Excerpt(s): The present invention relates to methods and compositions for the treatment and prophylaxis of arteriosclerosis and/or xanthoma. Throughout the world, in recent years, the tendency has been for the incidence of coronary artery disease and arteriosclerosis, including atherosclerosis, to increase, even in those countries in which hitherto they have not been prevalent. Amongst the factors implicated in such an increase are changes in lifestyle, including the "Western" meat-rich diet, and the adoption of such a diet even in countries where it is not traditional, and the general increase in the average age of the population. As a result, these diseases and arteriosclerosis, in particular, are widely feared as arteriosclerosis is a well known potential cause of unexpected death, for example by such sequelae of arteriosclerosis as myocardial infarction. One of the main risk factors implicated in these diseases is a high blood plasma lipid level, particularly a high blood plasma cholesterol level. There have, therefore, been many attempts to use an agent which lowers the cholesterol level in order to prevent and cure these diseases, and many compounds have been developed which, to a greater or lesser extent, have this effect. For example, one such compound, which has been very successful and is very well known is pravastatin, which is a lipid regulating agent and is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (hereinafter referred to as "HMG-CoA reductase inhibitor") which is believed to act on the rate-determining step of cholesterol biosynthesis. It has been reported that coronary arteriosclerosis and xanthoma may be prevented in rabbits receiving pravastatin, but its efficacy remains insufficient ›Biochimica et Biophysica Acta, 960, 294-302 (1988)!. Studies to control coronary arteriosclerosis and xanthoma have been carried out using a combination of two lipid regulating agents, pravastatin and cholestyramine, which is well known as an agent for lowering lipoprotein levels, but the efficacy of this combination also remains insufficient ›Atherosclerosis, 83, 69-80 (1990)!. Web site: http://www.delphion.com/details?pn=US05798375__ •

Use of coenzyme Q.sub.10 in combination with HMG-CoA reductase inhibitor therapies Inventor(s): Folkers; Karl A. (Austin, TX), Langsjoen; Per H. (Temple, TX), Willis; Richard A. (Austin, TX) Assignee(s): Karl Folkers Foundation for Biomedical and Clinical Research (austin, Tx) Patent Number: 5,316,765 Date filed: September 19, 1991 Abstract: Disclosed are methods for inhibiting the side effects attendant treatment with HMG-CoA reductase inhibitors. Treatment of a patient with and HMG-CoA reductase inhibitor in combination with coenzyme Q.sub.10 provides a reduction in patient cholesterol levels and guards against typical HMG-CoA reductase-inhibitor side effects, most notably liver dysfunction and cardiac dysfunction. The combination of lovastatin, an HMG-CoA reductase inhibitor, and coenzyme Q.sub.10 in ratios of between 1:2 to 1:29 provide significant enhancement of a patient's caridac condition. By way of example, other HMG-CoA reductase inhibitors which may be included in the claimed combinations include pravastatin, compactin, fluvastatin, dalvastatin, simvastatin, BMY 22089, GR-95030, HR-780, CI-981, SQ 33,600, and BMY 22566 and XU-62-320. Excerpt(s): The field of the present invention relates to methods and compositions for reducing side effects HMG-CoA reductase inhibitor therapy particularly those related to the physiologically depressed levels of coenzyme Q.sub.10 in the animal. Most particularly, the invention provides methods effective for the reduction of cholesterol

Patents 85

using an HMG-CoA reductase inhibitor, while reducing and/or inhibiting the side effects clinically linked to the use of HMG-CoA reductase inhibitors, such as liver dysfunction, musculoskeletal, nervous system/psychiatric, cardiac dysfunction, skin and special senses disorders. The invention also provides specifically defined formulations which include a mixture of an HMG-CoA reductase inhibitor and coenzyme Q.sub.10. Coronary artery disease is the major cause of death in Western countries. Hypercholesterolemia is known to be a primary risk factor for death from coronary artery disease. It is known that 50% or more of the total body cholesterol in humans is derived from intrinsic biosynthesis. It is also known that a rate-limiting step of major significance in the biosynthesis of cholesterol is at the level of the enzyme known as 3-hydroxy-3-methylglutaryl-coenzyme A reductase or HMG-CoA reductase. This enzyme then was logical for inhibition to reduce the intrinsic biosynthesis of cholesterol toward reducing the risk factor of hypercholesterolemia and coronary artery death. Alberts et al. described the isolation, structure and biochemical properties of an active inhibitor of HGMCoA reductase which they named mevinolin. The scientific name, mevinolin, introduced in 1980, corresponds to the subsequent trademark name, MEVACOR.RTM. This chemical substance is 1,2,6,7,8,8a-hexahydro-.beta.,.delta.dihydroxy-2,6-dimethyl-8-(2-methyl-1 -oxobutoxy)-1-naphthaleneheptanoic acid.delta.lactone. Web site: http://www.delphion.com/details?pn=US05316765__

Patent Applications on Pravastatin 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 pravastatin: •

Compositions for improving lipid content in the blood Inventor(s): Kondo, Tatsuhito; (Tokyo, JP), Nakayama, Masato; (Kitakatsushika-gun, JP), Ohsawa, Tsuneki; (Tokyo, JP), Shimizu, Ippei; (Tokyo, JP), Takagi, Ikuo; (Matsudo-shi, JP), Torizumi, Yasuhiro; (Ryugasaki-shi, JP) Correspondence: Frishauf, Holtz, Goodman & Chick, PC; 767 Third Avenue; 25th Floor; New York; NY; 10017-2023; US Patent Application Number: 20030216357 Date filed: April 22, 2003 Abstract: The present invention relates to compositions for lowering the total amount of cholesterol in the blood and methods of using the compositions. The compositions are a mixture of pravastatin and one or more vitamins selected from riboflavins, d-.alpha.tocopherols, ascorbic acids and inositol hexanicotinate. Excerpt(s): This is a Continuation-in-Part Application of International Application No. PCT/JP01/09257 filed Oct. 22, 2001 which is incorporated herein by reference in its entirety. The present invention relates to compositions for lowering the total amount of cholesterol in the blood, said compositions comprising pravastatin and one or more vitamins selected from the group consisting of riboflavins, d-.alpha.-tocopherols,

10

This has been a common practice outside the United States prior to December 2000.

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ascorbic acids and inositol hexanicotinate. Pravastatin exhibits activity in lowering the total amount of cholesterol in the blood due to HMG-CoA reductase inhibition in vivo. In addition, it is known that each of riboflavins, d-.alpha.-tocopherols, ascorbic acids and inositol hexanicotinate themselves have activity in lowering the total amount of cholesterol in the blood. Furthermore, it is also known that the total amount of cholesterol in the blood can be kept at a low level and the amount of d-.alpha.tocopherols and ascorbic acid in the body is decreased by HMG-CoA reductase inhibitors and this can be supplemented by the combination of an HMG-COA reductase inhibitor and a d-.alpha.-tocopherol or an ascorbic acid (Japanese Patent Application Publication (Kohyo) No. Hei 8-505853). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Conversion of compactin to pravastatin by actinomadura Inventor(s): Davis, Joseph; (Azle, TX), Demain, Arnold; (Wellesley, MA), Peng, Yulin; (Cambridge, MA), Yashphe, Jacob; (Meusseret-Zion, IL) Correspondence: Testa, Hurwitz & Thibeault, Llp; High Street Tower; 125 High Street; Boston; MA; 02110; US Patent Application Number: 20010026934 Date filed: April 13, 2001 Abstract: A method for converting compactin to pravastatin is described. Compactin is provided and contacted with an agent derived from Actinomadura under conditions in which the agent converts compactin to pravastatin. Also described are an Actinomadura strain, an Actinomadura cell free extract, an Actinomadura hydroxylase, and a method for lowering cholesterol levels in mammals. Excerpt(s): This invention relates to methods for converting compactin to pravastatin using an agent derived from the filamentous bacterium Actinomadura, to methods for lowering cholesterol levels in mammals, and to Actinomadura and to Actinomadura hydroxylase. One of the major causes of atherosclerosis and coronary disease is attributed to high blood cholesterol levels. It has been estimated that at least about 50% of total body cholesterol is derived from de novo cholesterol synthesis. A major ratelimiting step in the cholesterol biosynthetic pathway is catalyzed by 3-hydroxy-3methylglutaryl (HMG)-CoA reductase. Compactin and pravastatin have been reported to be competitive inhibitors of HMG-CoA reductase, and the presence of either one can result in inhibition of cholesterol biosynthesis. Microbial hydroxylation of compactin can produce hydroxylated forms of compactin, e.g., pravastatin. Some hydroxylated forms are reportedly more effective than compactin as competitive inhibitors of HMGCoA. It has been reported that this hydroxylation can be effected to differing degrees by many different genera of fungi, and from the bacteria Nocardia and Streptomyces roseochromogenus and Streptomyces carbophilus. See, e.g., U.S. Pat. No. 5,179,013; U.S. Pat. No. 4,448,979; U.S. Pat. No. 4,346,227; U.S. Pat. No. 4,537,859; Canadian Patent No. 1,150,170; Canadian Patent No. 1,186,647; Serizawa et al., J. Antibiotics 36:887-891 (1983). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Genetic test to determine non-responsiveness to statin drug treatment Inventor(s): Rotter, Jerome I.; (Los Angeles, CA), Scheuner, Maren T.; (Manhattan Beach, CA), Taylor, Kent D.; (Santa Paula, CA), Yang, Huiying; (Cerritos, CA) Correspondence: Sidley Austin Brown & Wood; 555 West Fifth Street; Los Angeles; CA; 90013-1010; US Patent Application Number: 20020106657 Date filed: July 3, 2001 Abstract: In a method for detecting a genetic predisposition in a human for nonresponsiveness to statin drug treatment for coronary artery disease, nucleic acids comprising nucleotide sequences of the human lipoprotein lipase (LPL) gene are amplified and analyzed. Homozygosity for a variant allele in a non-coding or untranslated region of the 3' end of LPL, for example, LPL HindIII 2/2 or (TTTA).sub.n 4/4 genotypes, is linked to non-responsiveness to treatment with statin drugs, including lovastatin, pravastatin, simvastatin, atorvastatin, fluvastatin, or cerivastatin. Oligonucleotide primer sequences, primer sets, and genetic testing kits allow the practitioner to practice the method and thus better individualize the treatment and improve the care of patients with coronary artery disease. Excerpt(s): Throughout this application various publications are referenced within parentheses. The disclosures of these publications in their entireties are hereby incorporated by reference in this application in order to more fully describe the state of the art to which this invention pertains. This invention relates to the medical arts. In particular, it relates to the field of genetic testing methods and diagnostic kits. Statin drugs--the most potent lipid-lowering agents currently available--are 3-hydroxy-3methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors. They include lovastatin, pravastatin, simvastatin, atorvastatin, fluvastatin, and cerivastatin. All these statin drugs share a common mechanism of action and have similar toxicity profiles. (E. von Kreutz and G. Schluter, Preclinical safety evaluation of cerivastatin, a novel HMG-CoA reductase inhibitor, Am. J. Cardiol. 82(4B):11J-17J [1998];A. G. Ollson [1998]). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Interferon-statin combination therapy Inventor(s): Cantrell, Stephen B.; (Brentwood, TN) Correspondence: Stephen B. Cantrell, Dds, MD; 111 Mckays Court; Brentwood; TN; 37027; US Patent Application Number: 20030232033 Date filed: February 20, 2003 Abstract: A method for pharmacological treatment of cancer and other diseases is presented which includes the novel combination of a statin (Hmg-CoA reductase inhibitor, such as lovastatin, simvastatin, atorvastatin, cerivastatin, fluvastatin, pravastatin, or newer agents), with an interferon (such as interferon alfa-2b or others) or an angiogenesis inhibitor (a very similar and often overlapping group of drugs which inhibit blood vessel growth and maintenance, such as thalidomide, angiostatin, endostatin, or other agents), and also including concurrent administration of selenium and calcium. The method disclosed in this invention is useful because it can prove more effective than previously known therapies for certain diseases and because its use may

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be more tolerable, less disfiguring, and less expensive than other methods. The method here disclosed can be readily reproduced by any person skilled in the art of treating disease. Excerpt(s): This application claims the benefit of U.S. provisional patent application No. 60/359265 mailed Feb. 20, 2002 and received for filing Feb. 21, 2002. Not applicable. Not applicable. No drawings are pertinent to understanding, making, and using the present invention. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Lipid peroxide-lowering compositions Inventor(s): Kondo, Tatsuhito; (Tokyo, JP), Nakayama, Masato; (Kitakatsushika-gun, JP), Ohsawa, Tsuneki; (Tokyo, JP), Shimizu, Ippei; (Tokyo, JP), Takagi, Ikuo; (Matsudo-shi, JP), Torizumi, Yasuhiro; (Ryugasaki-shi, JP) Correspondence: Frishauf, Holtz, Goodman & Chick, PC; 767 Third Avenue; 25th Floor; New York; NY; 10017-2023; US Patent Application Number: 20030229124 Date filed: May 2, 2003 Abstract: Compositions having excellent blood lipid peroxide lowering activity are provided. In particular, compositions for lowering lipid peroxides in the blood which contain pravastatin together with at least one substance selected from the group consisting of taurine, pantethine and inositol hexanicotinate. Use of these compositions enables the provision of excellent preventive or remedial agents capable of lowering the concentration of lipid peroxides in the blood which show effects of injuring vascular endothelial cells, accelerating platelet aggregation, forming foam cells, etc. Excerpt(s): This is a Continuation-in-Part application of International Application No. PCT/JP01/09662 filed Nov. 5, 2001 which is incorporated herein by reference in its entirety. The present invention relates to blood lipid peroxide-lowering compositions consisting of pravastatin in combination with one or more substances selected from taurine, pantethine and inositol hexanicotinate. An increase in blood lipid peroxide levels causes damage to endothelial cells, enhances platelet aggregation, and promotes foam cell forming, all of which contribute to arteriosclerosis. Thus lipid peroxidelowering agents are considered to be useful agents. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Medicinal compositions for the prevention or treatment of cardiac failure Inventor(s): Chu, Chia-Wei; (Kaoshung-city, TW), Hsiao, Chia-Ling; (Chung-ho city, TW), Lee, Bai-Ching; (Taipei, TW), Lee, Tsung Ming; (Taipei-city, TW), Su, Shen-Fang; (Tainan-city, TW) Correspondence: Frishauf, Holtz, Goodman & Chick, PC; 767 Third Avenue; 25th Floor; New York; NY; 10017-2023; US Patent Application Number: 20030181500 Date filed: February 26, 2003

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Abstract: The present invention relates to pharmaceutical compositions, which contain a HMG-CoA reductase inhibitor selected from the group consisting of pravastatin, simvastatin, lovastatin, pitavastatin and ZD-4522 and an angiotensin II receptor antagonist and optionally further contain a calcium channel blocker. The compositions are for prevention or treatment of cardiac failure. Excerpt(s): This is a Continuation Application of PCT/JP10/07437 filed Aug. 29, 2001, which is incorporated herein by reference in its entirety. The present invention relates to pharmaceutical compositions for the prevention or treatment of cardiac failure, the prevention of ischemic coronary heart disease or the prevention of the recurrence of ischemic coronary heart disease, said pharmaceutical compositions containing a HMGCoA reductase inhibitor selected from the group consisting of pravastatin, simvastatin, lovastatin, pitavastatin and ZD-4522 and an angiotensin II receptor antagonist and optionally further containing a calcium channel blocker. The present invention also relates to methods for the prevention or treatment of cardiac failure, the prevention of ischemic coronary heart disease or the prevention of the recurrence of ischemic coronary heart disease, said methods comprising administering to a warm-blooded animal (particularly a human) in need of such treatment or prevention a pharmacologically effective amount of a pharmaceutical composition that contains a HMG-CoA reductase inhibitor selected from the group consisting of pravastatin, simvastatin, lovastatin, pitavastatin and ZD-4522 and an angiotensin II receptor antagonist and optionally further contains a calcium channel blocker. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

METHOD FOR PREVENTING, STABILIZING OR CAUSING REGRESSION OF ATHEROSCLEROSIS EMPLOYING A COMBINATION OF A CHOLESTEROL LOWERING DRUG AND AN ACE INHIBITOR Inventor(s): BERGEY, JAMES L.; (LANSDALE, PA), KAWANO, JAMES C.; (NARBERTH, PA), TSCHOLLAR, WERNER; (LAWRENCEVILLE, NJ), YONCE, CARY S.; (NEWTOWN, PA) Correspondence: Burton Rodney; Bristol-myers Squibb Company; P.O. Box 4000; Princeton; NJ; 085434000 Patent Application Number: 20030149101 Date filed: December 2, 1991 Abstract: A method is provided for slowing the progression of atherosclerosis in hypertensive or normotensive patients and reducing or eliminating atherosclerotic lesions in such patients by administering a combination of a cholesterol lowering drug such as pravastatin, and an ACE inhibitor, especially one containing a mercapto moiety, such as captopril or zofenopril. Excerpt(s): This application is a continuation-in-part of application Serial No. 524,266, filed May 15, 1990. The present invention relates to a method for preventing, stabilizing or causing regression of atherosclerosis in mammalian species by administering a combination of a cholesterol lowering drug, such as an HMG CoA reductase inhibitor, for example, pravastatin, and an ACE inhibitor, preferably an ACE inhibitor containing a mercapto moiety, such as captopril or zofenopril, and to a pharmaceutical combination for use in such method. The proatherosclerotic effect of elevated serum cholesterol on vascular tissue is well documented (Weinstein and Heider, "Protective action of calcium

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channel antagonists in atherogenesis and vascular injury," Am. J. Hypertens. 2: 20512,1989). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method for purification of pravastatin or a pharmacologically acceptable salt thereof Inventor(s): Hagisawa, Minoru; (Yokohama-shi, JP), Hamano, Kiyoshi; (Kawasaki-shi, JP), Kojima, Shunshi; (Kamakura-shi, JP), Sugio, Nobunari; (Funabashi-shi, JP), Suzuki, Mutsuo; (Fujimi-shi, JP), Takamatsu, Yasuyuki; (Iwaki-shi, JP) Correspondence: Frishauf, Holtz, Goodman & Chick, PC; 767 Third Avenue; 25th Floor; New York; NY; 10017-2023; US Patent Application Number: 20030204105 Date filed: April 16, 2003 Abstract: The present invention provides methods for purification of pravastatin or a pharmacologically acceptable salt thereof using a salting-out technique. Inorganic salts are added to an aqueous solution of pravastatin of a pharmacologically acceptable salt thereof which was obtained from culturing of microorganisms, to selectively precipitate the pravastatin or pharmacologically acceptable salt. Excerpt(s): This is a Continuation-in-Part Application of International Application No. PCT/JP01/09044 filed Oct. 15, 2001 which is incorporated herein by reference in its entirety. The present invention relates to a method for purification of pravastatin or a pharmacologically acceptable salt thereof, the method comprising use of a salting-out technique. As explained hereinbelow, pravastatin as well as several other statins are prepared by fermentation or culturing of appropriate microorganisms. However, as is well known in the art, the result of such fermentation is not only the desired pravastatin product but also impurities in the form of structurally closely related compounds or analogues. Workers in the art have, therefore, devised a number of purification methods to separate the purified product. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method for treating atherosclerosis employing an aP2 inhibitor and combination Inventor(s): Biller, Scott A.; (Hopewell, NJ), Jacobson, Bruce L.; (Mercerville, NJ), Jamil, Haris; (Newtown, PA), Kodukula, Krishna; (Princeton, NJ), Parker, Rex A.; (Titusville, NJ), Robl, Jeffrey A.; (Newtown, PA) Correspondence: Marla J Mathias; Bristol-myers Squibb Company; Patent Department; P O Box 4000; Princeton; NJ; 08543-4000; US Patent Application Number: 20020035064 Date filed: July 13, 2001 Abstract: A method is provided for treating atherosclerosis and related diseases, employing an aP2 inhibitor or a combination of an aP2 inhibitor and another antiatherosclerotic agent, for example, an HMG CoA reductase inhibitor such as pravastatin. Excerpt(s): The present invention relates to a method for treating atherosclerosis and related diseases, employing an aP2 inhibitor alone or in combination with another type

Patents 91

antiatherosclerotic agent. Fatty acid binding proteins (FABPs) are small cytoplasmic proteins which bind to fatty acids such as oleic acids which are important metabolic fuels and cellular regulators. Dysregulation of fatty acid metabolism in adipose tissue is a prominent feature of insulin resistance and the transition from obesity to non-insulin dependent diabetes mellitus (NIDDM or Type II diabetes). aP2, an abundant 14.6 KDa cytosolic protein in adipocytes, and one of a family of homologous intracellular fatty acid binding proteins (FABPs), is involved in the regulation of fatty acid trafficking in adipocytes and mediates fatty acid fluxes in adipose tissue. G. S. Hotamisligil et al, "Uncoupling of Obesity from Insulin Resistance Through a Targeted Mutation in aP2, the Adipocyte Fatty Acid Binding Protein", Science, Vol. 274, Nov. 22, 1996, pp. 13771379, report that aP2-deficient mice placed on a high fat diet for several weeks developed dietary obesity, but, unlike control-mice on a similar diet, did not develop insulin resistance or diabetes. Hotamisligil et al conclude that "aP2 is central to the pathway that links obesity to insulin resistance" (Abstract, page 1377). In accordance with the present invention, a method is provided for treating atherosclerosis wherein a therapeutically effective amount of a drug which inhibits aP2 (aP2 inhibitor) is administered to a human patient in need of treatment. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

METHODS AND COMPOSITIONS FOR ASSOCIATED WITH PULMONARY DISEASE

INHIBITING

INFLAMMATION

Inventor(s): HARLAN, JOHN M.; (SEATTLE, WA), LIU, LI; (REDMOND, WA), WINN, ROBERT K.; (BAINBRIDGE ISLAND, WA) Correspondence: Campbell & Flores Llp; 4370 LA Jolla Village Drive; 7th Floor; San Diego; CA; 92122; US Patent Application Number: 20010006656 Date filed: February 17, 1999 Abstract: The present invention provides an aerosol formulation of a 3-hydroxy-3methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitor. The HMG-CoA reductase inhibitor can be, for example, a statin such as lovastatin, pravastatin, simvastatin, cerivastatin, fluvastatin, atorvastatin or mevastatin. The invention also provides a method of treating a pulmonary disease with an aerosol formulation of a HMG-CoA reductase inhibitor. Excerpt(s): The present invention relates generally to the fields of medicine and molecular pathology and, more specifically, to methods of treating an inflammatory lung disease. A variety of pulmonary diseases are associated with inflammation, including acute and chronic diseases. Pulmonary diseases associated with inflammation include, for example, asthma, interstitial pneumonitis, emphysema, chronic bronchitis, adult respiratory distress syndrome (ARDS) and cystic fibrosis. Many of the lung diseases associated with inflammation have a significant impact on human health, quality of life and productivity. For example, approximately 5% of the United States population has signs or symptoms of asthma. Chronic obstructive pulmonary disease, including chronic bronchitis and emphysema, is the fourth leading cause of death in the United States. In addition, the United States has approximately 100,000 cases of adult respiratory distress syndrome (ARDS), which can follow systemic or pulmonary insults. Cystic fibrosis is the most common lethal genetic disease in Caucasians, affecting approximately one in 2,000 births among Americans of European descent. Therefore, inflammatory lung diseases have a major impact on human health.

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Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Microbial process for preparing pravastatin Inventor(s): Albrecht, Karoly; (Budapest, HU), Ambrus, Gabor; (Budapest, HU), Andor, Attila; (Budapest, HU), Barta, Istvan; (Budapest, HU), Birinesik, Laszlo; (Miskolc, HU), Boros, Sandor; (Szod, HU), Horvath, Gyula; (Budapest, HU), Igloy, Margit Bidlo Nee; (Budapest, HU), Ilkoy, Eva; (Budapest, HU), Jekkel, Antonia; (Budapest, HU), Konya, Attila; (Szolnok, HU), Lang, Ildiko; (Budapest, HU), Salat, Janso; (Budapest, HU), Somogyi, Gyorgy; (Budapest, HU), Suto, Julianna Mozes Nee; (Budapest, HU), Szabo, Istvan; (Budapest, HU) Correspondence: Steven J. Lee; Kenyon & Kenyon; One Broadway; New York; NY; 10004; US Patent Application Number: 20020081675 Date filed: December 5, 2001 Abstract: The present invention relates to a new microbial process for the preparation of the compound formula (I) 1from a compound of general formula (II) 2wherein R stands for an alkali metal or ammonium ion, by the submerged cultivation of a mold strain able to 6.beta.-hydroxylate a compound of the Formula (II) in aerobic fermentation and by the separation and purification of the product of Formula (I) formed in the course of the bioconversion. The process comprises cultivating a strain of Mortierella maculata filamentous mold species that is able to 6.beta.-hydroxylate a compound of the general Formula (II), on a nutrient medium containing assimilable carbon and nitrogen sources and mineral salts and separating the product formed from the fermentation broth, then isolating the compound of formula (I) and purifying the same. Novel strains of Mortierella maculata are also disclosed. Excerpt(s): The present invention relates to a process for the preparation of pravastatin, and particularly to a microbial process for the manufacture of pravastatin on an industrial scale. and other related compounds (compactin, mevinolin, simvastatin) are the competitive inhibitors of the HMG-CoA reductase enzyme [A. Endo et al., J. Antibiot. 29, 1346-1348 (1976); A. Endo et al., FEBS Lett. 72, 323-326 (1976); C. H. Kuo et al., J. Org. Chem. 48, 1991 (1983)]. Pravastatin was first isolated by M. Tanaka et al. (unpublished results) from the urine of a dog during the examination of the compactin metabolism (Arai, M. et al., Sankyo Kenkyusyo Nenpo, 40, 1-38, 1988). Currently pravastatin is a cholesterol lowering agent with the most advantageous action mechanism in the therapy. Its most important character is tissue selectivity, i.e., it inhibits the cholesterol synthesis at the two main sites of the cholesterogenesis, such as in the liver and in the small intestine, while in other organs the intracellular enzyme limiting effect is hardly detectable, At the same time the cholesterol biosynthesis limiting effect of mevinolin and simvastatin is significant in most of the organs (T. Koga et al., Biochim. Biophys. Acta, 1045, 115-120, 1990). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Novel combination of an ADP-receptor blocking antiplatelet drug and a thromboxane A2 receptor antagonist and a method for inhibiting thrombus formation employing such combination Inventor(s): Ogletree, Martin L.; (Newtown, PA) Correspondence: Stephen B. Davis; Bristol-myers Squibb Company; Patent Department; P O Box 4000; Princeton; NJ; 08543-4000; US Patent Application Number: 20030109543 Date filed: November 15, 2002 Abstract: A method is provided for inhibiting platelet aggregation and thrombus formation by administering to a patient an ADP-receptor blocking antiplatelet drug, such as clopidogrel, in combination with a thromboxane A.sub.2 receptor antagonist, such as ifetroban, and optionally a cholesterol lowering drug, such as an HMG CoA reductase inhibitor, for example, pravastatin. Excerpt(s): The present invention relates to a novel combination of an ADP-receptor blocking antiplatelet drug, such as clopidogrel, and a thromboxane A.sub.2 receptor antagonist such as ifetroban, and optionally a cholesterol lowering drug, such as pravastatin, and to a method for inhibiting platelet aggregation and thrombus formation employing such combination. including pharmaceutically acceptable acid addition salts thereof, preferably the hydrogen sulfate salt, and is disclosed in U.S. Pat. Nos. 4,529,596 to Aubert et al and 4,847,265 to Badorc et al as having blood platelet aggregation inhibiting activity and anti-thrombotic activity and thus useful in inhibiting or preventing arterial and venous thrombosis. U.S. Pat. No. 5,576,328 to Herbert et al discloses that clopidogrel may be employed in secondary prevention of ischemic events such as myocardial infarction, unstable or stable angina, acute reocclusion after percutaneous transluminal coronary angioplasty (PTCA), restenosis after PTCA, thrombotic stroke, transient ischemic attack, reversible ischemic neurological deficit, and intermittent claudication. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Novel forms of pravastatin sodium Inventor(s): Aronhime, Judith; (Rechovot, IL), Kri, Vilmos; (Debrecen, HU), Nagyne, Edit Arvai; (Debrecen, HU), Szabo, Csaba; (Debrecen, HU) Correspondence: Kenyon & Kenyon; One Broadway; New York; NY; 10004; US Patent Application Number: 20010041809 Date filed: December 14, 2000 Abstract: New polymorphic forms of pravastatin sodium are provided. Each of the new forms is selectively obtained by crystallization from different solvent systems, each solvent system having a protic component, and by controlling the rate of crystallization through temperature. The new polymorphic forms are suitable for use as active substances of pharmaceutical dosage forms for reduction of serum cholesterol levels in the bloodstream. Excerpt(s): This application claims the benefit under 35 U.S.C.sctn. 119(e) of U.S. Provisional Patent Application No. 60/170,685, filed Dec. 14, 1999 and U.S. Provisional Patent Application No. 60/190,649, filed Mar. 20, 2000. The present invention relates to statins, and more particularly to novel polymorphic forms of pravastatin sodium.

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According to U.S. Pat. No. 4,346,227, incorporated herein by reference, pravastatin is reported as having been first isolated as a metabolite of compactin by M. Tanaka et al. during a study of compactin metabolism. The '227 patent discloses the isolation of pravastatin in its lactone form, as the methyl ester of the free carboxylic acid and as the monosodium salt of the free carboxylic acid ("pravastatin sodium"). Pravastatin sodium was analyzed by nuclear magnetic resonance spectroscopy, infrared ("IR") spectroscopy, ultraviolet spectroscopy and thin layer chromatography. Pravastatin sodium was analyzed in solid form by IR spectroscopy using the conventional technique of comixing with potassium bromide ("KBr") and then compressing to form a KBr window or pellet. The IR spectrum of the pravastatin sodium obtained by absorption bands at 3400, 2900, 1725, 1580 cm.sup.-1. All other spectral measurements are repeated on pravastatin sodium in solution. 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 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

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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 •

Pharmaceutical composition containing a combination of a statin and aspirin and method Inventor(s): Jain, Nemichand B.; (Cranbury, NJ), Ullah, Ismat; (Cranbury, NJ) Correspondence: Marla J. Mathias; Bristol-myers Squibb Company; Patent Department; P.O. Box 4000; Princeton; NJ; 08543-4000; US Patent Application Number: 20020034546 Date filed: April 2, 2001 Abstract: A pharmaceutical composition is provided which is useful for cholesterol lowering and reducing the risk of a myocardial infarction, which includes a statin, such as pravastatin, lovastatin, simvastatin, atorvastatin, cerivastatin or fluvastatin, in combination with aspirin, in a manner to minimize interaction of aspirin with the statin and minimize side effects of aspirin. A method for lowering cholesterol and reducing risk of a myocardial infarction employing such composition is also provided. Excerpt(s): The present invention relates to a pharmaceutical composition which includes a statin cholesterol lowering agent and aspirin in a manner to minimize interaction of aspirin with the statin, for use in lowering cholesterol and reducing risk of a myocardial infarction, and to a method for lowering cholesterol and reducing risk of a myocardial infarction employing such composition. The use of aspirin for reducing the risk of a myocardial infarction and the use of statins for lowering cholesterol and preventing or treating atherosclerosis and cardiovascular disease and cerebrovascular disease are well documented. In fact, it is not uncommon that patients having elevated cholesterol levels who are at high risk for a myocardial infarction take both a statin and aspirin. However, use of both a statin and aspirin may require special care to insure that drug interaction, including physical and chemical incompatibility, and side effects, are kept to a minimum while achieving maximum benefit from these drugs. With regard to possible drug interaction, aspirin is an acid, while some of the statins, such as pravastatin, atorvastatin and cerivastatin, are alkali salts. Thus, mixing of such statins (alkali salts) with aspirin could result in aspirin hydrolysis as well as statin degradation. Pravastatin, on the other hand, is also a very acid labile compound. When pravastatin and aspirin are combined, the aspirin could cause pravastatin degradation which could result in lower bioavailability of pravastatin. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Pharmaceutical compositions Inventor(s): Belder, Rene; (Hopewell, NJ), McGovern, Mark E.; (Miami Beach, FL) Correspondence: Stephen B. Davis; Bristol-myers Squibb Company; Patent Department; P O Box 4000; Princeton; NJ; 08543-4000; US Patent Application Number: 20020183383 Date filed: February 27, 2001

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Abstract: The instant invention provides methods and pharmaceutical compositions for reducing LDL cholesterol levels in mammals comprising the administration of a therapeutically effective amount of greater than 40 mg once per day of pravastatin, or a pharmaceutically acceptable salt or ester thereof, to a mammal in need of such treatment. Excerpt(s): The present invention relates to a pharmaceutical composition, preferably in the form of a tablet, which includes a single dose of more than 40 mg of pravastatin. Pravastatin sodium (hereinafter referred to as pravastatin) is a 3-hydroxy-3methylglutaryl Coenzyme A (HMG-CoA) reductase inhibitor that has been evaluated in clinical studies since 1985, and marketed as a cholesterol lowering agent since 1991. Clinical trial experience with pravastatin is extensive. Pravastatin has gained approval for slowing progression of coronary and carotid atherosclerosis in patients with hypercholesterolemia. Pravastatin has been shown to reduce the risk of myocardial infarction, coronary and cardiovascular mortality and total mortality in asymptomatic patients. Pravastatin has been well tolerated and all studies have demonstrated excellent safety experience. Despite this background, the dose response pattern for pravastatin has not been fully explored. A standard dose of pravastatin is 40 mg/day. Studies of pravastatin have been done with total daily doses of 10-80 mg of pravastatin, but it is not believed that single doses of more than 40 mg have been studied. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Pravastatin pharmaceutical formulations and methods of their use Inventor(s): Butler, Jackie; (Westmeath, IE), Devane, John; (Roscommon, IE), Stark, Paul; (Westmeath, IE) Correspondence: Finnegan, Henderson, Farabow,; Garrett & Dunner, L.L.P.; 1300 I Street, N.W.; Washington; DC; 20005-3315; US Patent Application Number: 20030176502 Date filed: January 10, 2003 Abstract: The present invention relates to formulations comprising a therapeutically effective amount of pravastatin, or a pharmaceutically acceptable salt thereof, and methods of their use. The present formulations and methods are designed to release little or no pravastatin in the stomach but release a therapeutic amount of pravastatin in the small intestine, thereby limiting systemic exposure of the body to pravastatin and maximizing hepatic-specific absorption of the drug. The formulations and methods of the present invention are particularly useful for treating and/or preventing conditions that are benefited by decreasing levels of lipids and/or cholesterol in the body. Excerpt(s): This application claims the benefit of priority of U.S. Provisional Patent Applications Nos. 60/347,775, filed Jan. 11, 2002, and 60/407,269, filed Sep. 3, 2002, the entire disclosure of each of which is incorporated by reference herein. Pravastatin is an HMG-CoA reductase inhibitor that lowers blood lipid levels by reducing cholesterol biosynthesis in the liver. It is a competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, which catalyzes the conversion of HMG-CoA to mevalonate, an early rate-limiting step in cholesterol biosynthesis. Pravastatin sodium (sold as PRAVACHOL.RTM.) is commercially available for oral administration in 10 mg, 20 mg, 40 mg and 80 mg tablets. It is generally prescribed for lowering cholesterol and blood lipid levels. The drug has been found to be useful in preventing coronary events in hypercholesterolemic patients that do not have coronary heart disease and as a

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secondary preventative of coronary cardiovascular events in hypercholesterolemic patients that have coronary artery disease. The drug is also used as an adjunctive therapy (to supplement dietary restrictions and exercise) in reducing elevated Total-C, LDL-C, Apo B and TG levels, and to increase HDL-C levels in patients with primary hypercholesterolemia and mixed dyslipidemia (Fredrickson Type IIa and IIb), elevated serum triglyceride levels (Fredrickson Type IV), and primary dysbetalipoproteinemia (Fredrickson Type III) in patients who do not respond adequately to dietary restrictions. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Pravastatin sodium substantially free of pravastatin lactone and epi-pravastatin, and compositions containing same Inventor(s): Deak, Lajos; (Debrecen, HU), Forgacs, Ilona; (Debrecen, HU), Keri, Vilmos; (Debrecen, HU), Nagyne, Arvai Edit; (Debrecen, HU), Szabo, Csaba; (Debrecen, HU) Correspondence: Kenyon & Kenyon; One Broadway; New York; NY; 10004; US Patent Application Number: 20020082295 Date filed: October 5, 2001 Abstract: The present invention provides pravastatin sodium substantially free of pravastatin lactone and epiprava, the C-6 epimer of pravastatin. The present invention further provides a novel process for recovering pravastatin sodium from a fermentation broth in such high purity. The process includes the stages of forming an solution of the compound by extraction, obtaining an ammonium salt of pravastatin from the solution, purifying the ammonium salt of the compound and transposing the salt of the compound to pravastatin sodium. Excerpt(s): The present application claims priority under 35 U.S.C. 119(e) to U.S. Provisional Application No. 60/238,276, filed Oct. 5, 2000, which is incorporated herein by reference. The present invention relates to statins and more particularly to pravastatin sodium and processes for isolating it as a product of enzymatic hydroxylation of compactin from a fermentation broth. Statin drugs are currently the most therapeutically effective drugs available for reducing the level of LDL in the blood stream of a patient at risk for cardiovascular disease. This class of drugs includes pravastatin as well as compactin, lovastatin, simvastatin, fluvastatin and atorvastatin. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Process for the preparation of sodium salts of statins Inventor(s): Kumar, M. Laltshmi; (Andhra Pradesh, IN), Kumar, Parveen; (Haryana, IN), Narula, Pardeep; (Delhi, IN), Raman, S.; (Tamil Nadu, IN) Correspondence: Jayadeep R Deshmukh; Ranbaxy Laboratories Limited; Suite 2100; 600 College Road East; Princeton; NJ; 08540; US Patent Application Number: 20030050502 Date filed: September 4, 2002 Abstract: A process for the preperation of sodium salts of statins, namely Compactin, Lovastatin and Pravastatin.

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Excerpt(s): The "statins" are a family of compounds that are usually inhibitors of 3hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in cholesterol biosynthesis. As HMG-CoA reductase inhibitors, the statins are able to reduce plasma cholesterol levels in various mammalian species, including humans and are therefore effective in the treatment of hypercholesterolaemia. Of all the statins known only two are produced directly by fermentation. These are Lovastatin (also called mevinolin or monacolin-K) and Compactin (also called mevastatin or ML-236B). Other statins are produced either chemically or enzymatically derived from Lovastatin or Compactin. One of these is Pravastatin, which has found favour recently as a more potent HMG-CoA reductase inhibitor than Lovastatin or Compactin and is disclosed in U.S. Pat. No. 4,346,227. Preparation of sodium salts of these compounds has been described in U.S. Pat. Nos. 4,448,979; 4,346,227; and 4,447,626. The methods employ use of alkali, acid, solvents, ion exchange chromatography followed by freeze drying operation using either the lactone or methyl ester form of Pravastatin as the raw material. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Process for the purification of pravastatin Inventor(s): Hagisawa, Minoru; (Yokohama-shi, JP), Hamano, Kiyoshi; (Kawasaki-shi, JP), Kojima, Shunshi; (Kamakura-shi, JP), Sugio, Nobunari; (Funabashi-shi, JP), Suzuki, Mutsuo; (Fujimi-shi, JP), Takamatsu, Yasuyuki; (Iwaki-shi, JP) Correspondence: Frishauf, Holtz, Goodman & Chick, PC; 767 Third Avenue; 25th Floor; New York; NY; 10017-2023; US Patent Application Number: 20030216596 Date filed: April 16, 2003 Abstract: A method of isolating or purifying pravastatin or its pharmaceutically acceptable salt characterized by involving, in the process of isolating or purifying pravastatin or its pharmacologically acceptable salt, the step of extracting pravastatin using an organic solvent represented by the formula CH.sub.3CO.sub.2R wherein R represents an alkyl group having 3 or more carbon atoms or the step of decomposing impurities using an inorganic acid or an inorganic base; and compositions containing pravastatin sodium thus obtained. Excerpt(s): This is a Continuation-in-Part Application of International Application No. PCT/JP01/09045 filed Oct. 15, 2001 which is incorporated herein by reference in its entirety. The present invention relates to a process for the isolation or purification of pravastatin or a pharmacologically acceptable salt thereof which process comprises carrying out a step of extracting pravastatin and analogues thereof using an organic solvent having formula CH.sub.3CO.sub.2R (wherein R represents an alkyl group having three or more carbons); relates to a process for the isolation or purification of pravastatin or a pharmacologically acceptable salt thereof which process comprises performing a step comprising the decomposition of impurities using an inorganic acid; and relates to a process for the isolation or purification of pravastatin or a pharmacologically acceptable salt thereof which process comprises performing a step comprising the decomposition of impurities using an inorganic base. Further, the present invention relates to a process for isolating or purifying pravastatin or a pharmacologically acceptable salt thereof which combines two or more steps selected from the above-mentioned three steps.

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Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Stabilized pharmaceutically effective composition and pharmaceutical formulation comprising the same Inventor(s): Kerc, Janez; (Ljubljana, SI), Pflaum, Zlatko; (Domzale, SI) Correspondence: Bromberg & Sunstein Llp; 125 Summer Street; Boston; MA; 02110-1618; US Patent Application Number: 20030109584 Date filed: November 15, 2002 Abstract: Lovastatin, pravastatin, simvastatin, mevastatin, atorvastatin, and derivatives and analogs thereof are known as HMG-CoA reductase inhibitors and are used as antihypercholesterolemic agents. The majority of them are produced by fermentation using microorganisms of different species identified as species belonging to Aspergillus, Monascus, Nocardia, Amycolatopsis, Mucor or Penicillium genus, and some are obtained by treating the fermentation products using the methods of chemical synthesis or they are the products of total chemical synthesis. The aforementioned active substances may be destabilized by the environmental factors, their degradation may also be accelerated by interactions with other pharmaceutical ingredients, such as fillers, binders, lubricants, glidants and disintegrating agents, therefore the pharmaceutical ingredients and the process for preparation of the pharmaceutical formulation should be meticulously chosen to avoid the aforementioned undesired interactions and reactions. The present invention relates to a HMG-CoA reductase inhibitor which is stabilized by forming a homogeneous composition with a buffering substance or a basifying substance. This homogeneous composition is suitably used as the active substance in a pharmaceutical formulation for the treatment of hypercholesterolemia and hyperlipidemia. Excerpt(s): This application is a continuation-in-part of U.S. application Ser. No. 09/591,322 filed on Jun. 9, 2000, which is currently pending. Its disclosure is incorporated herein by reference. The present invention relates to a newly stabilized HMG-CoA reductase inhibitor which is used in a pharmaceutical formulation being particularly suitable for the treatment of hypercholesterolemia and hyperlipidemia. More precisely, the present invention relates to a stabilized and very homogeneous composition mixture comprising a HMG-CoA reductase inhibitor, such as atorvastatin, pravastatin, fluvastatin and cerivastatin, or pharmaceutically active salts thereof, as well as solid pharmaceutical formulations containing the aforementioned homogeneous composition mixture as an active substance. The present invention relates more particularly to a stabilized and very homogeneous composition mixture comprising a HMG CoA reductase inhibitor or its pharmaceutically active salts, as well as solid pharmaceutical formulations containing the aforementioned homogeneous composition mixture as an active substance and which has increased stability as determined by a small change of its pH value and lactone content under storage and/or handling conditions. The present invention relates most particularly to a stabilized and very homogeneous composition mixture comprising pravastatin or its pharmaceutically active salts, as well as solid pharmaceutical formulations containing the aforementioned homogeneous composition mixture as an active substance and which has increased stability as determined by a small change of its pH value and lactone content under storage and/or handling conditions. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Strains of saccharaothrix, process for producing pravastain using the strains and isolation process of (HMG)-CoA reductase Inventor(s): Chiu, Schung-Ching; (Taipei City, TW), Hong, Anderson C.; (Taipei City, TW), Lee, Fang-Yu; (Taichung County, TW), Lee, Ming-Liang; (Taichung County, TW) Correspondence: Blakely Sokoloff Taylor & Zafman; 12400 Wilshire Boulevard, Seventh Floor; Los Angeles; CA; 90025; US Patent Application Number: 20030199047 Date filed: February 27, 2002 Abstract: The present invention provides two new microorganism strains of Saccharothrix, designated as YS-44442 and YS-45494, a process of producing pravastatin using the strains, and an improved process for isolation of (HMG)-CoA reductase inhibitors. Excerpt(s): The present invention relates to two new microorganism strains of Saccharothrix, designated as YS-44442 and YS-45494, a process of producing pravastatin using the strains, and an improved process for isolation of (HMG)-CoA reductase inhibitors. It has been recognized that an elevated blood cholesterol level is one of the major risk factors to atherosclerotic diseases, specifically to coronary heart diseases. The monitor for the cholesterol biosynthesis is very helpful to control the diseases. 3hydroxy-3-methylglutaryl (HMG)-CoA reductase is the rate-limiting enzyme in the cholesterol biosynthesis. By inhibiting the activity of (HMG)-CoA reductase, blood cholesterol levels in the bodies can be effectively reduced. These (HMG)-CoA reductase inhibitors are very effective in lowering blood cholesterol level in most animals including human. Pravastatin is even more active than compactin and lovastatin, and has been applied in the treatment of hypercholesterolemia (Nara, F et al. Curr. Genet. 23: 28-32 (1993)). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Sublingual use of inhibitors in the biosynthesis of cholesterol Inventor(s): Weiss, Sol; (Reseda, CA) Correspondence: Mitchell, Silberberg & Knupp, Llp; Trident Center; 11377 West Olympic Boulevard; Los Angeles; CA; 90064; US Patent Application Number: 20030100493 Date filed: June 4, 2002 Abstract: The present invention is a method introducing the sublingual placement of statin drugs whose names include: Fluvastatin, Atorvastatin, Lovastatin, Pravastatin and Simvastatin for heart related and other vascular emergencies. Current research challenges are developing many new derivatives and new classes of these HMG-CoA reductase inhibitors, which alter the biosynthesis of cholesterol. This method applies these medications (statin drugs) in a form such as sublingual (under the tongue) for rapid absorption and immediate high blood levels similar to that of nitroglycerin. The advantage of this method is that it will benefit those who are stricken with strokes and heart attacks by therefore saving lives and costs of medical care. Excerpt(s): This application contains subject matter of my provisional application Serial No. 60/306,977, filed Jul. 19, 2001, entitled Sublingual Use of Inhibitors in the Biosynthesis of Cholesterol, and in my provisional application Serial No. 60/314,532,

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filed Aug. 23, 2001, entitled Amendments to Serial No. 60/306,977. There is disclosed a method and combination of components to administer statin drugs in a beneficial method and manner. This method includes the sublingual administration of drugs selected from the class of drugs known as statin drugs. In addition to the method, there is disclosed a method and attendant components for administering sublingual medication or medications for emergency stabilization of ruptured plaques; suppression of thrombus or aggregation of platelets; alteration of inflammatory responses; improvement of endothelial function; reduction in cell death and augmentation of vasodilation. Disclosed is the combination of medications, such as a statin drug and nitroglycerin, and others, in sublingual administration. In addition, it has been found that combinations of other statin class drugs with other cholesterol lowering drugs such as niacin and other complications rupture, thrombus and platelet aggregation, inflammation, compromised endothelial function, vasoconstriction and cell death. These statin medications both by their own merits and in combinations with other drugs will lend to more beneficial and/or synergistic effects. Statins are like the new aspirins for use in the field of emergency medicine. The new Heart Protection Study (HPS) done in England reflects this latest and major breakthrough study of the statin class of drugs showing a reduction of adverse major vascular events over 5.5 years of treatment in high-risk patients. Most everyone is aware of the beneficial role of aspirin in emergency medicine. Furthering this theory of use ill medical emergencies are new reports of statins reducing infarct size in stroke patients. Statins favor endothelial nitric oxide synthase (eNOS) and block inducible nitric oxide synthase (iNOS) effects. These effects are neuroprotective by preserving blood flow and limiting neurological insult. Another ongoing study shows that a neurotoxin, Beta-Amyloid, derived from the Amyloid Precursor Protein (APP), was found embedded in the membranes of cells as disclosed in Alzheimer's disease, multiple sclerosis, vascular inflammations and other degenerative changes. Similar changes are recognized in patients with coronary artery and vascular diseases therefore implicating the plaque deposits occur elsewhere in the body as a result of the high cholesterol contents in tissues. High cholesterol induces these toxic changes. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Synergistic combination of pravastatin and aspirin and method Inventor(s): Belder, Rene; (Hopewell, NJ), Natarajan, Kannan; (Newtown, PA) Correspondence: Stephen B. Davis; Bristol-myers Squibb Company; Patent Department; P O Box 4000; Princeton; NJ; 08543-4000; US Patent Application Number: 20030013688 Date filed: April 23, 2002 Abstract: A synergistic combination of pravastatin and aspirin is provided which is formed of 40 mg pravastatin and 81 mg or higher of aspirin, preferably 81 mg aspirin or 325 mg of aspirin. A method for preventing, inhibiting or reducing risk of onset of cardiovascular events or cerebrovascular events employing such synergistic combination is also provided. Excerpt(s): This application claims priority from U.S. Provisional Application No. 60/299,959 filed Jun. 21, 2001, the entirety of which is incorporated herein by reference. The use of aspirin for reducing the risk of a myocardial infarction and the use of statins for lowering cholesterol and preventing or treating atherosclerosis and cardiovascular disease and cerebrovascular disease are well documented. In fact, it is not uncommon

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that patients having elevated cholesterol levels who are at high risk for a myocardial infarction take both a statin and aspirin. U.S. Pat. No. 6,235,311 to Ullah et al discloses a combination of a statin including pravastatin and aspirin for preventing, reducing and/or treating elevated cholesterol levels, atherosclerosis, cardiovascular events and disease including coronary events and cerebrovascular events, and coronary artery disease and/or cerebrovascular disease. Ullah et al teach use of pravastatin in amounts from about 10 to about 80 mg and aspirin in amounts from about 10 to about 800 mg. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Tnf-alpha inhibitors Inventor(s): Funatsu, Masami; (Neyagawa-shi Osaka, JP), Ikeya, Kazuaki; (Ikoma-gun, Nara, JP), Naruo, Ken-ichi; (Sanda-shi, Hyogo, JP), Odaka, Hiroyuki; (Kobe-shi, Hyogo, JP), Sugiyama, Yasuo; (Kawanishi-shi, Hyogo, JP), Suzuki, Yoshiharu; (Suita-shi Osaka, JP) Correspondence: Wenderoth, Lind & Ponack, L.L.P.; 2033 K Street N. W.; Suite 800; Washington; DC; 20006-1021; US Patent Application Number: 20030018040 Date filed: August 8, 2002 Abstract: There is provided a TNF-.alpha. inhibitor comprising at least one compound selected from cerivastatin, atorvastatin, simvastatin, pravastatin, itavastatin and (+)-(3R, 5S)-7-[4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl-N-methanesulfonylamino) pyrimidin-5-yl]-3,5-dihydroxy-6 (E)-heptenoic acid, or a salt thereof, which is excellent in the preventing and treating effects to TNF-.alpha. -associated diseases such as inflammatory disease and has the sufficiently excellent nature as a medicine, such as absence of side effect. Excerpt(s): The present invention relates to a TNF-.alpha. inhibitor, useful as an agent for preventing or treating TNF-.alpha. -associated diseases, for example, inflammatory diseases, which contains at least one compound selected from cerivastatin, atorvastatin, simvastatin, pravastatin, itavastatin and (+)-(3R, 5S)-7-[4-(4-fluorophenyl) -6-isopropyl2-(N-methyl-N-methanesulfonylamino)pyrimidin-5-yl]-3,5-dihyd- roxy-6(E)-heptenoic acid, or a salt thereof. TNF (tumor necrosis factor)-.alpha. is thought to play an important role in various diseases. For example, in rheumatoid arthritis which is an inflammatory disease, it is thought that production of TNF-.alpha. is enhanced and this causes destruction of the joint tissue. Development of a TNF-.alpha. ( inhibitor is desired which is excellent in the effect of preventing and treating inflammatory diseases, and has the sufficiently excellent nature as a medicine such as absence of the side effect. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Triglyceride depressant composition Inventor(s): Kondo, Tatsuhito; (Tokyo, JP), Nakayama, Masato; (Kitakatsushika-gun, JP), Ohsawa, Tsuneki; (Tokyo, JP), Shimizu, Ippei; (Tokyo, JP), Takagi, Ikuo; (Matsudo-shi, JP), Torizumi, Yasuhiro; (Ryugasaki-shi, JP) Correspondence: Frishauf, Holtz, Goodman & Chick, PC; 767 Third Avenue; 25th Floor; New York; NY; 10017-2023; US Patent Application Number: 20040009986 Date filed: June 18, 2003 Abstract: A blood triglyceride depressant composition which comprises pravastatin and one or more members selected from the group consisting of (1) pantethine, (2) inositol hexanicotinate, (3) a combination drug containing a riboflavin compound, a tocopherol compound and an ascorbic acid compound, and (4) a combination drug containing a tocopherol compound and an ascorbic acid compound. Excerpt(s): This is Continuation-in-Part Application of International Application No. PCT/JP01/10912 filed Dec. 12, 2001 which is incorporated herein by reference in its entirety. The present invention relates to a triglyceride depressant composition that contains pravastatin in combination with one or more substances selected from the group consisting of (1) pantethine, (2) inositol hexanicotinate, (3) a combination drug that contains a riboflavin derivative, a tocopherol derivative and an ascorbic acid derivative, and (4) a combination drug that contains a tocopherol derivative and an ascorbic acid derivative. The relationships between triglyceride levels in the blood and arteriosclerotic diseases are not fully understood, unlike the clearly established relationships between blood cholesterol levels and coronary arteriosclerotic diseases. However, dyslipidemia is becoming increasingly more recognized as a risk factor for arteriosclerotic diseases. In addition, it has become clear that hyperglyceridemia induces insulin resistance and significantly contributes to arteriosclerosis (References: eg., Modern Physician, Vol. 18 No.1, 1998, pp. 53-56, and pp. 69-71). 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 pravastatin, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “pravastatin” (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 pravastatin. You can also use this procedure to view pending patent applications concerning pravastatin. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 5. BOOKS ON PRAVASTATIN Overview This chapter provides bibliographic book references relating to pravastatin. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on pravastatin include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.

Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “pravastatin” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “pravastatin” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “pravastatin” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

Pravastatin Sodium: Over 10 Years of Experience: A Worldwide Review of Clinical Articles from the Scientific Literature by Marianne J. Legato (Editor); ISBN: 0919839584; http://www.amazon.com/exec/obidos/ASIN/0919839584/icongroupinterna

Chapters on Pravastatin In order to find chapters that specifically relate to pravastatin, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and pravastatin 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 “pravastatin” (or synonyms) into the “For these words:” box.

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CHAPTER 6. PERIODICALS AND NEWS ON PRAVASTATIN Overview In this chapter, we suggest a number of news sources and present various periodicals that cover pravastatin.

News Services and Press Releases One of the simplest ways of tracking press releases on pravastatin 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 “pravastatin” (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 pravastatin. 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 “pravastatin” (or synonyms). The following was recently listed in this archive for pravastatin: •

FDA grants 6-month exclusivity extension for Pravachol for pediatric trial Source: Reuters Medical News Date: October 31, 2002

•

Bristol-Myers' Pravachol wins pediatric indication, additional exclusivity Source: Reuters Industry Breifing Date: October 31, 2002

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•

Pravastatin curbs proteinuria in hypertensives, independently of lipid lowering Source: Reuters Industry Breifing Date: July 18, 2002

•

FDA panel supports Bristol-Myers Squibb's Pravachol, aspirin combo Source: Reuters Industry Breifing Date: July 18, 2002

•

Pravastatin and aspirin work together to cut cardiovascular disease risk Source: Reuters Industry Breifing Date: January 12, 2004

•

Coronary plaque volume is reduced with pravastatin therapy Source: Reuters Industry Breifing Date: November 21, 2003

•

India's Ranbaxy gets US FDA nod for generic Pravachol Source: Reuters Industry Breifing Date: October 03, 2003

•

Israel's Teva gets tentative US nod for generic Pravachol Source: Reuters Industry Breifing Date: May 20, 2002

•

Benefits of pravastatin in CHD patients sustained over long term Source: Reuters Industry Breifing Date: April 19, 2002

•

Pravastatin reduces mortality in patients with and without CHD Source: Reuters Industry Breifing Date: March 26, 2002

•

FDA panel rejects pravastatin/aspirin combo Source: Reuters Health eLine Date: January 18, 2002

•

FDA panel rejects approval of Bristol-Myers pravastatin/aspirin combo Source: Reuters Industry Breifing Date: January 18, 2002

•

Higher dose pravastatin formulation approved by FDA Source: Reuters Medical News Date: January 09, 2002

•

Pravastatin helps cut cholesterol in HIV patients Source: Reuters Industry Breifing Date: August 28, 2001

•

Pravastatin reduces levels of both small and large LDL particles Source: Reuters Industry Breifing Date: August 27, 2001

•

Pravastatin may have anti-inflammatory effects Source: Reuters Medical News Date: July 03, 2001

•

FDA cites Bristol-Myers Squibb for misleading Pravachol ad Source: Reuters Industry Breifing Date: May 17, 2001

Periodicals and News

•

Pravastatin reduces risk of cardiovascular events in older patients with CHD Source: Reuters Industry Breifing Date: May 14, 2001

•

Bristol-Myers' Pravachol, Merck's Zocor lower marker of inflammation Source: Reuters Industry Breifing Date: March 21, 2001

•

Bristol-Myers' Pravachol may inhibit protein linked to heart disease Source: Reuters Industry Breifing Date: March 21, 2001

•

Pravastatin significantly reduces risk of ischemic stroke Source: Reuters Industry Breifing Date: January 23, 2001

•

Pravastatin significantly reduces diabetes risk in middle-aged men Source: Reuters Industry Breifing Date: January 22, 2001

•

Cerivastatin superior to pravastatin for LDL reduction Source: Reuters Industry Breifing Date: January 03, 2001

•

Pravastatin improves long-term outcome of patients with unstable angina Source: Reuters Industry Breifing Date: December 06, 2000

•

Cholesterol reduction with pravastatin not associated with worsened well-being Source: Reuters Industry Breifing Date: December 01, 2000

•

Pravastatin reduces risk of cardiac events in wide range of patient subgroups Source: Reuters Industry Breifing Date: October 17, 2000

•

Pravastatin use moderately reduces stroke risk in patients with CHD Source: Reuters Industry Breifing Date: August 03, 2000

•

FDA advisers vote against OTC Pravachol to treat high cholesterol Source: Reuters Industry Breifing Date: July 17, 2000

•

FDA advisers vote against OTC Pravachol Source: Reuters Health eLine Date: July 14, 2000

•

FDA adds geriatric use precaution to Bristol-Myers Squibb's Pravachol Source: Reuters Industry Breifing Date: July 04, 2000

•

FDA clears new use for Bristol-Myers Squibb's pravachol tablets Source: Reuters Industry Breifing Date: June 13, 2000

•

Pravastatin reduces BP in patients with hypertension plus hypercholesterolemia Source: Reuters Medical News Date: January 10, 2000

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Grapefruit juice increases bioavailability of atorvastatin but not of pravastatin Source: Reuters Medical News Date: August 26, 1999

•

Long-term pravastatin therapy reduces C-reactive protein levels in MI survivors Source: Reuters Medical News Date: July 20, 1999

•

Pravastatin reduces hospital admissions for cardiovascular disease Source: Reuters Medical News Date: March 23, 1999

•

Pravastatin reduces stroke risk after MI in patients with moderately high lipids Source: Reuters Medical News Date: January 25, 1999 The NIH

Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “pravastatin” (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 “pravastatin” (or synonyms). If you know the name of a company that is relevant to pravastatin, you can go to any stock trading Web site (such as http://www.etrade.com/) and

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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 “pravastatin” (or synonyms).

Academic Periodicals covering Pravastatin Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to pravastatin. In addition to these sources, you can search for articles covering pravastatin that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

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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 pravastatin. 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 pravastatin. 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

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following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to pravastatin: HMG-CoA Reductase Inhibitors •

Systemic - U.S. Brands: Baycol; Lescol; Lipitor; Mevacor; Pravachol; Zocor http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202284.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.

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APPENDICES

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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant 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.

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•

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

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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm

•

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

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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp

•

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

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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

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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/

•

Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

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Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html

•

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.

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•

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 “pravastatin” (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 2225 4 477 24 10 2740

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 “pravastatin” (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.

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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.

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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on pravastatin 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 pravastatin. 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 pravastatin. 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 “pravastatin”:

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Coronary Disease http://www.nlm.nih.gov/medlineplus/coronarydisease.html Diabetes http://www.nlm.nih.gov/medlineplus/diabetes.html Heart Attack http://www.nlm.nih.gov/medlineplus/heartattack.html Heart Diseases http://www.nlm.nih.gov/medlineplus/heartdiseases.html Metabolic Syndrome X http://www.nlm.nih.gov/medlineplus/metabolicsyndromex.html Stroke http://www.nlm.nih.gov/medlineplus/stroke.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 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 pravastatin. 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/

Patient Resources

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WebMDHealth: 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 pravastatin. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with pravastatin. 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 pravastatin. 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 “pravastatin” (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 “pravastatin”. 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 “pravastatin” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months.

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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 “pravastatin” (or a synonym) into the search box, and click “Submit Query.”

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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.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.

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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)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 129

•

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/

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•

Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

•

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 131

•

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/

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•

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

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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •

ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html

•

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

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PRAVASTATIN DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] 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] Acidity: The quality of being acid or sour; containing acid (hydrogen ions). [EU] Acyl: Chemical signal used by bacteria to communicate. [NIH] Acylation: The addition of an organic acid radical into a molecule. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] 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] Adjunctive Therapy: Another treatment used together with the primary treatment. Its purpose is to assist the primary treatment. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, 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] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]

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

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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] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]

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] Albuminuria: More than normal amounts of a protein called albumin in the urine. Albuminuria may be a sign of kidney disease. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alkaline: Having the reactions of an alkali. [EU] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allograft: An organ or tissue transplant between two humans. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Ameliorated: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [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

Dictionary 137

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] 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] 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] Angina: Chest pain that originates in the heart. [NIH] Angina Pectoris: The symptom of paroxysmal pain consequent to myocardial ischemia usually of distinctive character, location and radiation, and provoked by a transient stressful situation during which the oxygen requirements of the myocardium exceed the capacity of the coronary circulation to supply it. [NIH] 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] Angiogenesis inhibitor: A substance that may prevent the formation of blood vessels. In anticancer therapy, an angiogenesis inhibitor prevents the growth of blood vessels from surrounding tissue to a solid tumor. [NIH] Angioplasty: Endovascular reconstruction of an artery, which may include the removal of atheromatous plaque and/or the endothelial lining as well as simple dilatation. These are procedures performed by catheterization. When reconstruction of an artery is performed surgically, it is called endarterectomy. [NIH] Angiotensin-Converting Enzyme Inhibitors: A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [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]

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Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticholinergic: An agent that blocks the parasympathetic nerves. Called also parasympatholytic. [EU] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antidepressant: A drug used to treat depression. [NIH] 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] Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antihypertensive: An agent that reduces high blood pressure. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antineoplastic Agents: Substances that inhibit or prevent the proliferation of neoplasms. [NIH]

Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antiproliferative: Counteracting a process of proliferation. [EU] Antipruritic: Relieving or preventing itching. [EU] Antispasmodic: An agent that relieves spasm. [EU] Antithrombotic: Preventing or interfering with the formation of thrombi; an agent that so acts. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Aorta: The main trunk of the systemic arteries. [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] Apolipoproteins A: Lipoproteins found in human blood serum in the high-density and very-high-density lipoprotein fraction (HDL, VHDL). They consist of several different

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polypeptides, the most important of which are apolipoprotein A-I and A-II. They maintain the structural integrity of the HDL particles and are activators of lecithin:cholesterol acyltransferase (LCAT). Atherosclerotic patients show low apolipoprotein A levels and these apolipoproteins are either absent or present in extremely low plasma concentration in Tangier disease. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] 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] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arcus Senilis: A corneal disease in which there is a deposition of phospholipid and cholesterol in the corneal stroma and anterior sclera. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatic: Having a spicy odour. [EU] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriolosclerosis: Sclerosis and thickening of the walls of the smaller arteries (arterioles). Hyaline arteriolosclerosis, in which there is homogeneous pink hyaline thickening of the arteriolar walls, is associated with benign nephrosclerosis. Hyperplastic arteriolosclerosis, in which there is a concentric thickening with progressive narrowing of the lumina may be associated with malignant hypertension, nephrosclerosis, and scleroderma. [EU] 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] Ascorbic Acid: A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant. [NIH] Aseptic: Free from infection or septic material; sterile. [EU]

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Aspergillosis: Infections with fungi of the genus Aspergillus. [NIH] Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied in cancer prevention. [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] Atenolol: A cardioselective beta-adrenergic blocker possessing properties and potency similar to propranolol, but without a negative inotropic effect. [NIH] Atmospheric Pressure: The pressure at any point in an atmosphere due solely to the weight of the atmospheric gases above the point concerned. [NIH] Atrial: Pertaining to an atrium. [EU] Atrial Fibrillation: Disorder of cardiac rhythm characterized by rapid, irregular atrial impulses and ineffective atrial contractions. [NIH] Autodigestion: Autolysis; a condition found in disease of the stomach: the stomach wall is digested by the gastric juice. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autonomic: Self-controlling; functionally independent. [EU] 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] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Barbiturate: A drug with sedative and hypnotic effects. Barbiturates have been used as sedatives and anesthetics, and they have been used to treat the convulsions associated with epilepsy. [NIH] Baroreflex: A negative feedback system which buffers short-term changes in blood pressure. Increased pressure stretches blood vessels which activates pressoreceptors (baroreceptors) in the vessel walls. The net response of the central nervous system is a reduction of central

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sympathetic outflow. This reduces blood pressure both by decreasing peripheral vascular resistance and by lowering cardiac output. Because the baroreceptors are tonically active, the baroreflex can compensate rapidly for both increases and decreases in blood pressure. [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] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Beta blocker: A drug used to slow the heart rate and reduce pressure inside blood vessels. It also can regulate heart rhythm. [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] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones. [NIH] Bile duct: A tube through which bile passes in and out of the liver. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Biliary Tract: The gallbladder and its ducts. [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] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] 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

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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] Bladder: The organ that stores urine. [NIH] Blastomycosis: A fungal infection that may appear in two forms: 1) a primary lesion characterized by the formation of a small cutaneous nodule and small nodules along the lymphatics that may heal within several months; and 2) chronic granulomatous lesions characterized by thick crusts, warty growths, and unusual vascularity and infection in the middle or upper lobes of the lung. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Body Fluids: Liquid components of living organisms. [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] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breakdown: A physical, metal, or nervous collapse. [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Buffers: A chemical system that functions to control the levels of specific ions in solution.

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When the level of hydrogen ion in solution is controlled the system is called a pH buffer. [NIH]

Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [NIH] Calcification: Deposits of calcium in the tissues of the breast. Calcification in the breast can be seen on a mammogram, but cannot be detected by touch. There are two types of breast calcification, macrocalcification and microcalcification. Macrocalcifications are large deposits and are usually not related to cancer. Microcalcifications are specks of calcium that may be found in an area of rapidly dividing cells. Many microcalcifications clustered together may be a sign of cancer. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium channel blocker: A drug used to relax the blood vessel and heart muscle, causing pressure inside blood vessels to drop. It also can regulate heart rhythm. [NIH] Candidiasis: Infection with a fungus of the genus Candida. It is usually a superficial infection of the moist cutaneous areas of the body, and is generally caused by C. albicans; it most commonly involves the skin (dermatocandidiasis), oral mucous membranes (thrush, def. 1), respiratory tract (bronchocandidiasis), and vagina (vaginitis). Rarely there is a systemic infection or endocarditis. Called also moniliasis, candidosis, oidiomycosis, and formerly blastodendriosis. [EU] 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] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Captopril: A potent and specific inhibitor of peptidyl-dipeptidase A. It blocks the conversion of angiotensin I to angiotensin II, a vasoconstrictor and important regulator of arterial blood pressure. Captopril acts to suppress the renin-angiotensin system and inhibits pressure responses to exogenous angiotensin. [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] Carcinogenic: Producing carcinoma. [EU] 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] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] Cardioselective: Having greater activity on heart tissue than on other tissue. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH]

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Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Carnitine: Constituent of striated muscle and liver. It is used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. [NIH] Carotid Arteries: Either of the two principal arteries on both sides of the neck that supply blood to the head and neck; each divides into two branches, the internal carotid artery and the external carotid artery. [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] Catabolism: Any destructive metabolic process by which organisms convert substances into excreted compounds. [EU] Catheter: A flexible tube used to deliver fluids into or withdraw fluids from the body. [NIH] Catheterization: Use or insertion of a tubular device into a duct, blood vessel, hollow organ, or body cavity for injecting or withdrawing fluids for diagnostic or therapeutic purposes. It differs from intubation in that the tube here is used to restore or maintain patency in obstructions. [NIH] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell 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] Cellobiose: A disaccharide consisting of two glucose units in beta (1-4) glycosidic linkage. Obtained from the partial hydrolysis of cellulose. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Centrifugation: A method of separating organelles or large molecules that relies upon differential sedimentation through a preformed density gradient under the influence of a gravitational field generated in a centrifuge. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebrospinal: Pertaining to the brain and spinal cord. [EU]

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Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrotendinous Xanthomatosis: A primary fatty degeneration of the cornea occurring physiologically as an arcus senilis. [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] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chemotaxis: The movement of cells or organisms toward or away from a substance in response to its concentration gradient. [NIH] Chenodeoxycholic Acid: A bile acid, usually conjugated with either glycine or taurine. It acts as a detergent to solubilize fats for intestinal absorption and is reabsorbed by the small intestine. It is used as cholagogue, a choleretic laxative, and to prevent or dissolve gallstones. [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] Chlorophyll: Porphyrin derivatives containing magnesium that act to convert light energy in photosynthetic organisms. [NIH] Choleretic: A choleretic agent. [EU] Cholestanol: A cholesterol derivative found in human feces, gallstones, eggs, and other biological matter. [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] Cholestyramine: Strongly basic anion exchange resin whose main constituent is polystyrene trimethylbenzylammonium as Cl(-) anion. It exchanges chloride ions with bile salts, thus decreasing their concentration and that of cholesterol. It is used as a hypocholesteremic in diarrhea and biliary obstruction and as an antipruritic. [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 Disease: Disease or ailment of long duration. [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]

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Cilazapril: An angiotensin-converting enzyme inhibitor that is effective in the treatment of hypertension. Preliminary results also indicate its potential in the treatment of congestive heart failure. It is a prodrug that is hydrolyzed after absorption to its main metabolite cilazaprilat. [NIH] Citrus: Any tree or shrub of the Rue family or the fruit of these plants. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [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] 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] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] Colestipol: Highly crosslinked and insoluble basic anion exchange resin used as anticholesteremic. It may also may reduce triglyceride levels. [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] Collateral Circulation: Maintenance of blood flow to an organ despite obstruction of a principal vessel. Blood flow is maintained through small vessels. [NIH] Colloidal: Of the nature of a colloid. [EU] 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

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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] Compliance: Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Concomitant: Accompanying; accessory; joined with another. [EU] Congestive heart failure: Weakness of the heart muscle that leads to a buildup of fluid in body tissues. [NIH] 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]

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Constriction: The act of constricting. [NIH] Constriction, Pathologic: The condition of an anatomical structure's being constricted beyond normal dimensions. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Contractility: Capacity for becoming short in response to a suitable stimulus. [EU] 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] Conventional therapy: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional treatment. [NIH] Conventional treatment: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional therapy. [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] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Arteriosclerosis: Thickening and loss of elasticity of the coronary arteries. [NIH] Coronary Circulation: The circulation of blood through the coronary vessels of the heart. [NIH]

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] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance;

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and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Crystallization: The formation of crystals; conversion to a crystalline form. [EU] 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] Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [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] 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] Cytotoxic: Cell-killing. [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] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Depressive Disorder: An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent. [NIH] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH]

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Diabetes Insipidus: A metabolic disorder due to disorders in the production or release of vasopressin. It is characterized by the chronic excretion of large amounts of low specific gravity urine and great thirst. [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] Diarrhea: Passage of excessively liquid or excessively frequent stools. [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] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dihydroxy: AMPA/Kainate antagonist. [NIH] Dilatation: The act of dilating. [NIH] Dilatation, Pathologic: The condition of an anatomical structure's being dilated beyond normal dimensions. [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] Diltiazem: A benzothiazepine derivative with vasodilating action due to its antagonism of the actions of the calcium ion in membrane functions. It is also teratogenic. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [NIH] 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] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate

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precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dosage Forms: Completed forms of the pharmaceutical preparation in which prescribed doses of medication are included. They are designed to resist action by gastric fluids, prevent vomiting and nausea, reduce or alleviate the undesirable taste and smells associated with oral administration, achieve a high concentration of drug at target site, or produce a delayed or long-acting drug effect. They include capsules, liniments, ointments, pharmaceutical solutions, powders, tablets, etc. [NIH] Dose-dependent: Refers to the effects of treatment with a drug. If the effects change when the dose of the drug is changed, the effects are said to be dose dependent. [NIH] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] 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] Duodenum: The first part of the small intestine. [NIH] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] 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] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [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] Elasticity: Resistance and recovery from distortion of shape. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electrocardiography: Recording of the moment-to-moment electromotive forces of the heart as projected onto various sites on the body's surface, delineated as a scalar function of time. [NIH]

Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles

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with a net electric charge migrate in a solution under the influence of an electric current. [NIH]

Elementary Particles: Individual components of atoms, usually subatomic; subnuclear particles are usually detected only when the atomic nucleus decays and then only transiently, as most of them are unstable, often yielding pure energy without substance, i.e., radiation. [NIH] Emboli: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embolism: Blocking of a blood vessel by a blood clot or foreign matter that has been transported from a distant site by the blood stream. [NIH] Embolization: The blocking of an artery by a clot or foreign material. Embolization can be done as treatment to block the flow of blood to a tumor. [NIH] Embolus: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emergency Medicine: A branch of medicine concerned with an individual's resuscitation, transportation and care from the point of injury or beginning of illness through the hospital or other emergency treatment facility. [NIH] Emergency Treatment: First aid or other immediate intervention for accidents or medical conditions requiring immediate care and treatment before definitive medical and surgical management can be procured. [NIH] Emphysema: A pathological accumulation of air in tissues or organs. [NIH] Emulsions: Colloids of two immiscible liquids where either phase may be either fatty or aqueous; lipid-in-water emulsions are usually liquid, like milk or lotion and water-in-lipid emulsions tend to be creams. [NIH] Enalapril: An angiotensin-converting enzyme inhibitor that is used to treat hypertension. [NIH]

Endarterectomy: Surgical excision, performed under general anesthesia, of the atheromatous tunica intima of an artery. When reconstruction of an artery is performed as an endovascular procedure through a catheter, it is called atherectomy. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [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] Endostatin: A drug that is being studied for its ability to prevent the growth of new blood vessels into a solid tumor. Endostatin belongs to the family of drugs called angiogenesis inhibitors. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH]

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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] 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] 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] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Erythrocyte Deformability: Ability of erythrocytes to change shape as they pass through narrow spaces, such as the microvasculature. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Esterification: The process of converting an acid into an alkyl or aryl derivative. Most frequently the process consists of the reaction of an acid with an alcohol in the presence of a trace of mineral acid as catalyst or the reaction of an acyl chloride with an alcohol. Esterification can also be accomplished by enzymatic processes. [NIH] Estradiol: The most potent mammalian estrogenic hormone. It is produced in the ovary,

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placenta, testis, and possibly the adrenal cortex. [NIH] Estrogen: One of the two female sex hormones. [NIH] Estrogen receptor: ER. Protein found on some cancer cells to which estrogen will attach. [NIH]

Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Ethinyl Estradiol: A semisynthetic estrogen with high oral estrogenic potency. It is often used as the estrogenic component in oral contraceptives. [NIH] Evacuation: An emptying, as of the bowels. [EU] Excipient: Any more or less inert substance added to a prescription in order to confer a suitable consistency or form to the drug; a vehicle. [EU] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Extracellular: Outside a cell or cells. [EU] Extraction: The process or act of pulling or drawing out. [EU] Fallopian tube: The oviduct, a muscular tube about 10 cm long, lying in the upper border of the broad ligament. [NIH] 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] 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] Femoral: Pertaining to the femur, or to the thigh. [EU] Femoral Artery: The main artery of the thigh, a continuation of the external iliac artery. [NIH] Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee. [NIH] Fermentation: An enzyme-induced chemical change in organic compounds that takes place in the absence of oxygen. The change usually results in the production of ethanol or lactic acid, and the production of energy. [NIH] 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] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ,

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usually as a consequence of inflammation or other injury. [NIH] Flatus: Gas passed through the rectum. [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] Fluconazole: Triazole antifungal agent that is used to treat oropharyngeal candidiasis and cryptococcal meningitis in AIDS. [NIH] Fluoxetine: The first highly specific serotonin uptake inhibitor. It is used as an antidepressant and often has a more acceptable side-effects profile than traditional antidepressants. [NIH] Foam Cells: Lipid-laden macrophages originating from monocytes or from smooth muscle cells. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fosinopril: A phosphinic acid-containing angiotensin-converting enzyme inhibitor that is effective in the treatment of hypertension. It is a prodrug that is converted to its active metabolite fosinoprilat. [NIH] Free Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. [NIH] Freeze Drying: Method of tissue preparation in which the tissue specimen is frozen and then dehydrated at low temperature in a high vacuum. This method is also used for dehydrating pharmaceutical and food products. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Fungus: A general term used to denote a group of eukaryotic protists, including mushrooms, yeasts, rusts, moulds, smuts, etc., which are characterized by the absence of chlorophyll and by the presence of a rigid cell wall composed of chitin, mannans, and sometimes cellulose. They are usually of simple morphological form or show some reversible cellular specialization, such as the formation of pseudoparenchymatous tissue in the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental conditions, as moulds or yeasts. [EU] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gallstones: The solid masses or stones made of cholesterol or bilirubin that form in the gallbladder or bile ducts. [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.

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[NIH]

Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gemfibrozil: A lipid-regulating agent that lowers elevated serum lipids primarily by decreasing serum triglycerides with a variable reduction in total cholesterol. These decreases occur primarily in the VLDL fraction and less frequently in the LDL fraction. Gemfibrozil increases HDL subfractions HDL2 and HDL3 as well as apolipoproteins A-I and A-II. Its mechanism of action has not been definitely established. [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]

Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Giant Cells: Multinucleated masses produced by the fusion of many cells; often associated with viral infections. In AIDS, they are induced when the envelope glycoprotein of the HIV virus binds to the CD4 antigen of uninfected neighboring T4 cells. The resulting syncytium leads to cell death and thus may account for the cytopathic effect of the virus. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glioma: A cancer of the brain that comes from glial, or supportive, cells. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]

Glomerular Filtration Rate: The volume of water filtered out of plasma through glomerular capillary walls into Bowman's capsules per unit of time. It is considered to be equivalent to inulin clearance. [NIH] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glucocorticoids: A group of corticosteroids that affect carbohydrate metabolism (gluconeogenesis, liver glycogen deposition, elevation of blood sugar), inhibit corticotropin secretion, and possess pronounced anti-inflammatory activity. They also play a role in fat and protein metabolism, maintenance of arterial blood pressure, alteration of the connective tissue response to injury, reduction in the number of circulating lymphocytes, and functioning of the central nervous system. [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration

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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] Glutathione Peroxidase: An enzyme catalyzing the oxidation of 2 moles of glutathione in the presence of hydrogen peroxide to yield oxidized glutathione and water. EC 1.11.1.9. [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] Gonad: A sex organ, such as an ovary or a testicle, which produces the gametes in most multicellular animals. [NIH] Gonadal: Pertaining to a gonad. [EU] 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] Gram-positive: Retaining the stain or resisting decolorization by alcohol in Gram's method of staining, a primary characteristic of bacteria whose cell wall is composed of a thick layer of peptidologlycan with attached teichoic acids. [EU] Gram-Positive Bacteria: Bacteria which retain the crystal violet stain when treated by Gram's method. [NIH] Granule: A small pill made from sucrose. [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] Habitual: Of the nature of a habit; according to habit; established by or repeated by force of habit, customary. [EU] Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the major histocompatibility complex. [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

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other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [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] Heart Transplantation: The transference of a heart from one human or animal to another. [NIH]

Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [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 A: Hepatitis caused by hepatovirus. It can be transmitted through fecal contamination of food or water. [NIH] 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] Hepatovirus: A genus of Picornaviridae causing infectious hepatitis naturally in humans and experimentally in other primates. It is transmitted through fecal contamination of food or water. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Heterotrophic: Pertaining to organisms that are consumers and dependent on other organisms for their source of energy (food). [NIH] High blood cholesterol: Cholesterol is the most abundant steroid in animal tissues, especially in bile and gallstones. The relationship between the intake of cholesterol and its manufacture by the body to its utilization, sequestration, or excretion from the body is called the cholesterol balance. When cholesterol accumulates, the balance is positive; when it declines, the balance is negative. In 1993, the NHLBI National Cholesterol Education

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Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults issued an updated set of recommendations for monitoring and treatment of blood cholesterol levels. The NCEP guidelines recommended that total cholesterol levels and subfractions of high-density lipoprotein (HDL) cholesterol be measured beginning at age 20 in all adults, with subsequent periodic screenings as needed. Even in the group of patients at lowest risk for coronary heart disease (total cholesterol 200 mg/dL and HDL 35 mg/dL), the NCEP recommended that rescreening take place at least once every 5 years or upon physical examination. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Hydrochlorothiazide: A thiazide diuretic often considered the prototypical member of this class. It reduces the reabsorption of electrolytes from the renal tubules. This results in increased excretion of water and electrolytes, including sodium, potassium, chloride, and magnesium. It has been used in the treatment of several disorders including edema, hypertension, diabetes insipidus, and hypoparathyroidism. [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] Hydrophilic: Readily absorbing moisture; hygroscopic; having strongly polar groups that readily interact with water. [EU] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxy Acids: Organic compounds containing both the hydroxyl and carboxyl radicals. [NIH]

Hydroxylation: Hydroxylate, to introduce hydroxyl into (a compound or radical) usually by replacement of hydrogen. [EU] Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [NIH] Hyperlipidaemia: A general term for elevated concentrations of any or all of the lipids in the plasma, including hyperlipoproteinaemia, hypercholesterolaemia, etc. [EU] Hyperlipidemia: An excess of lipids in the blood. [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

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the number of cells. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hyperthyroidism: Excessive functional activity of the thyroid gland. [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] Hypnotic: A drug that acts to induce sleep. [EU] Hypolipidemic: A drug that lowers abnormally high plasma concentrations of cholesterol or triglycerides or both. [NIH] Hypotension: Abnormally low blood pressure. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Iliac Artery: Either of two large arteries originating from the abdominal aorta; they supply blood to the pelvis, abdominal wall and legs. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [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] 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] 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]

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Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Inorganic: Pertaining to substances not of organic origin. [EU] Inositol: An isomer of glucose that has traditionally been considered to be a B vitamin 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] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [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] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon Alfa-2b: A recombinant alfa interferon consisting of 165 amino acid residues with arginine in position 23 and histidine in position 34. It is used extensively as an antiviral and antineoplastic agent. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] 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]

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Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intracellular: Inside a cell. [NIH] Intracellular Membranes: Membranes of subcellular structures. [NIH] Intravascular: Within a vessel or vessels. [EU] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Inulin: A starch found in the tubers and roots of many plants. Since it is hydrolyzable to fructose, it is classified as a fructosan. It has been used in physiologic investigation for determination of the rate of glomerular function. [NIH] Ion Exchange: Reversible chemical reaction between a solid, often an ION exchange resin, and a fluid whereby ions may be exchanged from one substance to another. This technique is used in water purification, in research, and in industry. [NIH] Ionization: 1. Any process by which a neutral atom gains or loses electrons, thus acquiring a net charge, as the dissociation of a substance in solution into ions or ion production by the passage of radioactive particles. 2. Iontophoresis. [EU] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Ischemic stroke: A condition in which the blood supply to part of the brain is cut off. Also called "plug-type" strokes. Blocked arteries starve areas of the brain controlling sight, speech, sensation, and movement so that these functions are partially or completely lost. Ischemic stroke is the most common type of stroke, accounting for 80 percent of all strokes. Most ischemic strokes are caused by a blood clot called a thrombus, which blocks blood flow in the arteries feeding the brain, usually the carotid artery in the neck, the major vessel bringing blood to the brain. When it becomes blocked, the risk of stroke is very high. [NIH] Isopropyl: A gene mutation inducer. [NIH] Isosorbide: 1,4:3,6-Dianhydro D-glucitol. Chemically inert osmotic diuretic used mainly to treat hydrocephalus; also used in glaucoma. [NIH] Itraconazole: An antifungal agent that has been used in the treatment of histoplasmosis, blastomycosis, cryptococcal meningitis, and aspergillosis. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [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] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kidney stone: A stone that develops from crystals that form in urine and build up on the inner surfaces of the kidney, in the renal pelvis, or in the ureters. [NIH] Kinetics: The study of rate dynamics in chemical or physical systems. [NIH] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2.

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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] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]

Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Lethal: Deadly, fatal. [EU] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [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] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] 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] Lipid Peroxides: Peroxides produced in the presence of a free radical by the oxidation of unsaturated fatty acids in the cell in the presence of molecular oxygen. The formation of lipid peroxides results in the destruction of the original lipid leading to the loss of integrity of the membranes. They therefore cause a variety of toxic effects in vivo and their formation is considered a pathological process in biological systems. Their formation can be inhibited by antioxidants, such as vitamin E, structural separation or low oxygen tension. [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

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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] Lisinopril: An orally active angiotensin-converting enzyme inhibitor that has been used in the treatment of hypertension and congestive heart failure. [NIH] Lithium: An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight 6.94. Salts of lithium are used in treating manic-depressive disorders. [NIH]

Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Lovastatin: A fungal metabolite isolated from cultures of Aspergillus terreus. The compound is a potent anticholesteremic agent. It inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase (hydroxymethylglutaryl CoA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It also stimulates the production of low-density lipoprotein receptors in the liver. [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] Lubricants: Oily or slippery substances. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Magnesium Hydroxide: Magnesium hydroxide (Mg(OH)2). An inorganic compound that occurs in nature as the mineral brucite. It acts as an antacid with cathartic effects. [NIH] Magnesium Oxide: Magnesium oxide (MgO). An inorganic compound that occurs in nature as the mineral periclase. In aqueous media combines quickly with water to form magnesium hydroxide. It is used as an antacid and mild laxative and has many nonmedicinal uses. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into

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computerized images. The concept includes proton spin tomographic techniques. [NIH] Magnetic Resonance Spectroscopy: Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (magnetic resonance imaging). [NIH] Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune responseassociated (Ia) antigens, the immune response (Ir) genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Mammary: Pertaining to the mamma, or breast. [EU] Manic: Affected with mania. [EU] Mannans: Polysaccharides consisting of mannose units. [NIH] Mastitis: Inflammatory disease of the breast, or mammary gland. [NIH] Meat: The edible portions of any animal used for food including domestic mammals (the major ones being cattle, swine, and sheep) along with poultry, fish, shellfish, and game. [NIH]

Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medicament: A medicinal substance or agent. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Melanin: The substance that gives the skin its color. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Lipids: Lipids, predominantly phospholipids, cholesterol and small amounts of glycolipids found in membranes including cellular and intracellular membranes. These lipids may be arranged in bilayers in the membranes with integral proteins between the layers and peripheral proteins attached to the outside. Membrane lipids are required for active transport, several enzymatic activities and membrane formation. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Meningitis: Inflammation of the meninges. When it affects the dura mater, the disease is termed pachymeningitis; when the arachnoid and pia mater are involved, it is called leptomeningitis, or meningitis proper. [EU] Menopause: Permanent cessation of menstruation. [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] Mental Health: The state wherein the person is well adjusted. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU]

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Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [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] Microglia: The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Micro-organism: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microsomal: Of or pertaining to microsomes : vesicular fragments of endoplasmic reticulum formed after disruption and centrifugation of cells. [EU] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Mineralocorticoids: A group of corticosteroids primarily associated with the regulation of water and electrolyte balance. This is accomplished through the effect on ion transport in renal tubules, resulting in retention of sodium and loss of potassium. Mineralocorticoid secretion is itself regulated by plasma volume, serum potassium, and angiotensin II. [NIH] 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] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] 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] Monocyte: A type of white blood cell. [NIH] Mononuclear: A cell with one nucleus. [NIH]

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Monotherapy: A therapy which uses only one drug. [EU] Morphological: Relating to the configuration or the structure of live organs. [NIH] Motility: The ability to move spontaneously. [EU] Multidrug resistance: Adaptation of tumor cells to anticancer drugs in ways that make the drugs less effective. [NIH] Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myelin: The fatty substance that covers and protects nerves. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardial Ischemia: A disorder of cardiac function caused by insufficient blood flow to 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] Myopathy: Any disease of a muscle. [EU] Natriuresis: The excretion of abnormal amounts of sodium in the urine. [EU] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neomycin: Antibiotic complex produced by Streptomyces fradiae. It is composed of neomycins A, B, and C. It acts by inhibiting translation during protein synthesis. [NIH] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Nephropathy: Disease of the kidneys. [EU] Nephrosis: Descriptive histopathologic term for renal disease without an inflammatory component. [NIH] Nephrotic: Pertaining to, resembling, or caused by nephrosis. [EU] Nephrotic Syndrome: Clinical association of heavy proteinuria, hypoalbuminemia, and generalized edema. [NIH] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with

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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] Neurotoxin: A substance that is poisonous to nerve tissue. [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] 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] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Niceritrol: An ester of nicotinic acid that lowers cholesterol and triglycerides in total plasma and in the VLD- and LD-lipoprotein fractions. [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] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Normotensive: 1. Characterized by normal tone, tension, or pressure, as by normal blood pressure. 2. A person with normal blood pressure. [EU] 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

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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] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Oleic Acids: A group of fatty acids that contain 16 carbon atoms and a double bond at the omega 9 carbon. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the organ. [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] 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] Osteogenic sarcoma: A malignant tumor of the bone. Also called osteosarcoma. [NIH] Osteosarcoma: A cancer of the bone that affects primarily children and adolescents. Also called osteogenic sarcoma. [NIH] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] 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] 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] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU]

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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] Pancreatitis: Acute or chronic inflammation of the pancreas, which may be asymptomatic or symptomatic, and which is due to autodigestion of a pancreatic tissue by its own enzymes. It is caused most often by alcoholism or biliary tract disease; less commonly it may be associated with hyperlipaemia, hyperparathyroidism, abdominal trauma (accidental or operative injury), vasculitis, or uraemia. [EU] Parotid: The space that contains the parotid gland, the facial nerve, the external carotid artery, and the retromandibular vein. [NIH] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [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] Pelvic: Pertaining to the pelvis. [EU] Penis: The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Vascular Disease: Disease in the large blood vessels of the arms, legs, and feet. People who have had diabetes for a long time may get this because major blood vessels in their arms, legs, and feet are blocked and these limbs do not receive enough blood. The signs of PVD are aching pains in the arms, legs, and feet (especially when walking) and foot sores that heal slowly. Although people with diabetes cannot always avoid PVD, doctors say they have a better chance of avoiding it if they take good care of their feet, do not smoke, and keep both their blood pressure and diabetes under good control. [NIH] 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]

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Peritoneal Dialysis: Dialysis fluid being introduced into and removed from the peritoneal cavity as either a continuous or an intermittent procedure. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Peroxide: Chemical compound which contains an atom group with two oxygen atoms tied to each other. [NIH] P-Glycoprotein: A 170 kD transmembrane glycoprotein from the superfamily of ABC transporters. It serves as an ATP-dependent efflux pump for a variety of chemicals, including many antineoplastic agents. Overexpression of this glycoprotein is associated with multidrug resistance. [NIH] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. [NIH] Pharmaceutical Solutions: Homogeneous liquid preparations that contain one or more chemical substances dissolved, i.e., molecularly dispersed, in a suitable solvent or mixture of mutually miscible solvents. For reasons of their ingredients, method of preparation, or use, they do not fall into another group of products. [NIH] Pharmacodynamics: The study of the biochemical and physiological effects of drugs and the mechanisms of their actions, including the correlation of actions and effects of drugs with their chemical structure; also, such effects on the actions of a particular drug or drugs. [EU] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [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] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Pilot study: The initial study examining a new method or treatment. [NIH]

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Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [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] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] 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 Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Pneumonitis: A disease caused by inhaling a wide variety of substances such as dusts and molds. Also called "farmer's disease". [NIH] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., polypeptides, proteins, plastics). [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU]

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Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] 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] 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] Potentiate: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [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] Pravachol: Cholesterol-lowering drug developed by Bristol-Myers-Squibb. [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] 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] Pressoreceptors: Receptors in the vascular system, particularly the aorta and carotid sinus, which are sensitive to stretch of the vessel walls. [NIH] Primary Prevention: Prevention of disease or mental disorders in susceptible individuals or populations through promotion of health, including mental health, and specific protection, as in immunization, as distinguished from the prevention of complications or after-effects of existing disease. [NIH] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not itself active (i. e. an inactive precursor). [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] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Propranolol: A widely used non-cardioselective beta-adrenergic antagonist. Propranolol is

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used in the treatment or prevention of many disorders including acute myocardial infarction, arrhythmias, angina pectoris, hypertension, hypertensive emergencies, hyperthyroidism, migraine, pheochromocytoma, menopause, and anxiety. [NIH] 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] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Prostate gland: A gland in the male reproductive system just below the bladder. It surrounds part of the urethra, the canal that empties the bladder, and produces a fluid that forms part of semen. [NIH] Prostatic Hyperplasia: Enlargement or overgrowth of the prostate gland as a result of an increase in the number of its constituent cells. [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 Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific proteinbinding measures are often used as assays in diagnostic assessments. [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

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and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] 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 Embolism: Embolism in the pulmonary artery or one of its branches. [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]

Pupil: The aperture in the iris through which light passes. [NIH] Purifying: Respiratory equipment whose function is to remove contaminants from otherwise wholesome air. [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 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] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and

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interventional radiology or other planning and guiding medical radiology. [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] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] 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] Recombinant Proteins: Proteins prepared by recombinant DNA technology. [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] Reflective: Capable of throwing back light, images, sound waves : reflecting. [EU] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] 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] Renin: An enzyme which is secreted by the kidney and is formed from prorenin in plasma and kidney. The enzyme cleaves the Leu-Leu bond in angiotensinogen to generate angiotensin I. EC 3.4.23.15. (Formerly EC 3.4.99.19). [NIH] Renin-Angiotensin System: A system consisting of renin, angiotensin-converting enzyme, and angiotensin II. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming angiotensin I. The converting enzyme contained in the lung acts on angiotensin I in the plasma converting it to angiotensin II, the most powerful directly pressor substance known. It causes contraction of the arteriolar smooth muscle and has other indirect actions mediated through the adrenal cortex. [NIH] Reproductive system: In women, this system includes the ovaries, the fallopian tubes, the uterus (womb), the cervix, and the vagina (birth canal). The reproductive system in men includes the prostate, the testes, and the penis. [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]

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Respiratory distress syndrome: A lung disease that occurs primarily in premature infants; the newborn must struggle for each breath and blueing of its skin reflects the baby's inability to get enough oxygen. [NIH] Resuscitation: The restoration to life or consciousness of one apparently dead; it includes such measures as artificial respiration and cardiac massage. [EU] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Reverse Transcriptase Inhibitors: Inhibitors of reverse transcriptase (RNA-directed DNA polymerase), an enzyme that synthesizes DNA on an RNA template. [NIH] Rhabdomyolysis: Necrosis or disintegration of skeletal muscle often followed by myoglobinuria. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Riboflavin: Nutritional factor found in milk, eggs, malted barley, liver, kidney, heart, and leafy vegetables. The richest natural source is yeast. It occurs in the free form only in the retina of the eye, in whey, and in urine; its principal forms in tissues and cells are as FMN and FAD. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Risk patient: Patient who is at risk, because of his/her behaviour or because of the type of person he/she is. [EU] 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] 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] Sarcoidosis: An idiopathic systemic inflammatory granulomatous disorder comprised of epithelioid and multinucleated giant cells with little necrosis. It usually invades the lungs with fibrosis and may also involve lymph nodes, skin, liver, spleen, eyes, phalangeal bones, and parotid glands. [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH]

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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] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [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] Shivering: Involuntary contraction or twitching of the muscles. It is a physiologic method of heat production in man and other mammals. [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] 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] Simvastatin: A derivative of lovastatin and potent competitive inhibitor of 3-hydroxy-3methylglutaryl coenzyme A reductase (hydroxymethylglutaryl CoA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid

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hormone production. Due to the induction of hepatic LDL receptors, it increases breakdown of LDL-cholesterol (lipoproteins, LDL cholesterol). [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] 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] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] 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] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Spermatogenesis: Process of formation and development of spermatozoa, including spermatocytogenesis and spermiogenesis. [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] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side

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of the abdomen near the stomach. [NIH] Stabilization: The creation of a stable state. [EU] Stent: A device placed in a body structure (such as a blood vessel or the gastrointestinal tract) to provide support and keep the structure open. [NIH] 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] Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] 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] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Sublingual: Located beneath the tongue. [EU] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Substrate: A substance upon which an enzyme acts. [EU] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [NIH] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH]

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Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Taurine: 2-Aminoethanesulfonic acid. A conditionally essential nutrient, important during mammalian development. It is present in milk but is isolated mostly from ox bile and strongly conjugates bile acids. [NIH] Tendon: A discrete band of connective tissue mainly composed of parallel bundles of collagenous fibers by which muscles are attached, or two muscles bellies joined. [NIH] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] Testicular: Pertaining to a testis. [EU] 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] Thalidomide: A pharmaceutical agent originally introduced as a non-barbiturate hypnotic, but withdrawn from the market because of its known tetratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppresive and anti-angiogenic activity. It inhibits release of tumor necrosis factor alpha from monocytes, and modulates other cytokine action. [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] Thigh: A leg; in anatomy, any elongated process or part of a structure more or less comparable to a leg. [NIH] Thiostrepton: Polypeptide-containing antibiotic isolated from a species of Streptomyces in New Mexican soil. It appears to be highly active against gram-positive bacteria. In veterinary medicine, thiostrepton has been used in mastitis caused by gram-negative organisms and in dermatologic disorders. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytes: Blood cells that help prevent bleeding by causing blood clots to form. Also called platelets. [NIH] Thrombolytic: 1. Dissolving or splitting up a thrombus. 2. A thrombolytic agent. [EU] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU]

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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 specific function. [NIH] Tissue Distribution: Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tone: 1. The normal degree of vigour and tension; in muscle, the resistance to passive elongation or stretch; tonus. 2. A particular quality of sound or of voice. 3. To make permanent, or to change, the colour of silver stain by chemical treatment, usually with a heavy metal. [EU] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] Transcutaneous: Transdermal. [EU] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Triglyceride: A lipid carried through the blood stream to tissues. Most of the body's fat

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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] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] 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] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Uraemia: 1. An excess in the blood of urea, creatinine, and other nitrogenous end products of protein and amino acids metabolism; more correctly referred to as azotemia. 2. In current usage the entire constellation of signs and symptoms of chronic renal failure, including nausea, vomiting anorexia, a metallic taste in the mouth, a uraemic odour of the breath, pruritus, uraemic frost on the skin, neuromuscular disorders, pain and twitching in the muscles, hypertension, edema, mental confusion, and acid-base and electrolyte imbalances. [EU]

Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Uric: A kidney stone that may result from a diet high in animal protein. When the body breaks down this protein, uric acid levels rise and can form stones. [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] Ursodeoxycholic Acid: An epimer of chenodeoxycholic acid. It is a mammalian bile acid found first in the bear and is apparently either a precursor or a product of chenodeoxycholate. Its administration changes the composition of bile and may dissolve gallstones. It is used as a cholagogue and choleretic. [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] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular Resistance: An expression of the resistance offered by the systemic arterioles, and to a lesser extent by the capillaries, to the flow of blood. [NIH] Vasculitis: Inflammation of a blood vessel. [NIH] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which

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constriction, pathologic is used. [NIH] 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] Vasodilators: Any nerve or agent which induces dilatation of the blood vessels. [NIH] Vasomotor: 1. Affecting the calibre of a vessel, especially of a blood vessel. 2. Any element or agent that effects the calibre of a blood vessel. [EU] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Venous Thrombosis: The formation or presence of a thrombus within a vein. [NIH] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [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] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Vitreous: Glasslike or hyaline; often used alone to designate the vitreous body of the eye (corpus vitreum). [EU] 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] Warfarin: An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide. [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]

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Womb: A hollow, thick-walled, muscular organ in which the impregnated ovum is developed into a child. [NIH] Xanthoma: A tumour composed of lipid-laden foam cells, which are histiocytes containing cytoplasmic lipid material. Called also xanthelasma. [EU] 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]

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INDEX A Abdomen, 135, 142, 162, 164, 170, 180 Abdominal, 135, 160, 170, 171 Acceptor, 135, 169 Acetylcholine, 135, 168 Acidity, 135, 171 Acyl, 135, 153 Acylation, 82, 135 Adaptability, 135, 144 Adenosine, 135, 171 Adipocytes, 91, 135 Adipose Tissue, 91, 135, 163, 181 Adjunctive Therapy, 97, 135 Adrenal Cortex, 135, 148, 154, 173, 176 Adrenaline, 94, 135 Adrenergic, 135, 140, 151, 153, 173 Adverse Effect, 6, 135, 178 Aerobic, 92, 135 Aerosol, 91, 135 Affinity, 135, 136, 140, 163, 179 Agar, 136, 172 Age of Onset, 136, 183 Agonist, 94, 136, 151 Albumin, 136 Albuminuria, 23, 136 Algorithms, 136, 141 Alkaline, 136, 143 Alleles, 7, 136 Allograft, 14, 17, 20, 136 Alternative medicine, 110, 136 Ameliorated, 36, 136 Amino acid, 136, 137, 139, 150, 156, 157, 159, 161, 166, 170, 171, 175, 178, 180, 182, 183 Amyloid, 46, 101, 137 Anaesthesia, 137, 160 Anal, 137, 169 Anatomical, 137, 145, 148, 150, 160, 166, 177 Androgens, 135, 137, 149 Aneurysm, 137, 184 Angina, 7, 51, 93, 109, 137, 168, 174 Angina Pectoris, 51, 137, 174 Angiogenesis, 87, 137, 152 Angiogenesis inhibitor, 87, 137, 152 Angioplasty, 27, 47, 93, 137 Angiotensin-Converting Enzyme Inhibitors, 15, 137

Antagonism, 137, 150 Antibacterial, 137, 179 Antibiotic, 74, 137, 167, 179, 181 Antibodies, 137, 138, 164 Antibody, 136, 138, 146, 159, 161, 165, 179 Anticholinergic, 94, 138 Anticoagulant, 138, 174, 184 Antidepressant, 138, 155 Antidiabetic, 94, 138 Antidiabetic Agent, 94, 138 Antifungal, 138, 155, 162 Antigen, 136, 137, 138, 147, 156, 159, 160, 161, 165, 166 Antihypertensive, 42, 63, 78, 138 Anti-inflammatory, 16, 108, 138, 140, 149, 156 Anti-Inflammatory Agents, 138, 140, 149 Antineoplastic, 138, 149, 161, 171 Antineoplastic Agents, 138, 171 Antioxidant, 35, 138, 139 Antiproliferative, 14, 138 Antipruritic, 138, 145 Antispasmodic, 138, 155 Antithrombotic, 64, 138 Antiviral, 138, 161 Anxiety, 138, 174 Aorta, 64, 138, 160, 173, 184 Apolipoproteins, 27, 28, 30, 54, 138, 156, 163 Apolipoproteins A, 28, 138 Apoptosis, 44, 54, 139 Applicability, 10, 139 Aqueous, 81, 90, 139, 141, 149, 152, 163, 164 Arachidonic Acid, 139, 174 Arcus Senilis, 139, 145 Arginine, 7, 139, 161, 168 Aromatic, 139, 171 Arterial, 6, 10, 16, 23, 34, 93, 139, 143, 145, 156, 160, 168, 175, 181 Arteries, 24, 50, 51, 76, 138, 139, 142, 144, 148, 160, 162, 164, 166, 167 Arterioles, 139, 142, 143, 167, 183 Arteriolosclerosis, 139 Arteriosclerosis, 13, 77, 83, 84, 88, 103, 139, 160 Ascorbic Acid, 85, 86, 103, 139 Aseptic, 139, 169

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Aspergillosis, 140, 162 Aspirin, 15, 45, 95, 101, 108, 140 Assay, 11, 140 Astrocytes, 140, 166 Asymptomatic, 31, 96, 140, 170 Atenolol, 56, 140 Atmospheric Pressure, 16, 140 Atrial, 140, 184 Atrial Fibrillation, 140, 184 Autodigestion, 140, 170 Autoimmune disease, 140, 167 Autonomic, 10, 135, 140, 168, 180 Axillary, 140, 142 Axillary Artery, 140, 142 B Bacteria, 86, 135, 137, 138, 140, 141, 147, 152, 153, 154, 157, 166, 176, 179, 182 Bacteriophage, 140, 172 Bacterium, 86, 140, 147 Barbiturate, 140, 181 Baroreflex, 10, 140 Base, 82, 98, 141, 149, 156, 162, 183 Basophils, 141, 163 Benign, 139, 141, 157 Beta blocker, 10, 141 Beta-pleated, 137, 141 Bezafibrate, 29, 64, 94, 141 Bile, 16, 26, 62, 75, 141, 145, 155, 158, 164, 180, 181, 183 Bile Acids, 141, 180, 181 Bile Acids and Salts, 141 Bile duct, 141, 155 Biliary, 29, 58, 141, 145, 170 Biliary Tract, 141, 170 Bioavailability, 95, 110, 141 Biochemical, 14, 19, 48, 53, 79, 85, 136, 141, 171, 178 Biological response modifier, 141, 161 Biopsy, 141, 170 Biotechnology, 11, 12, 77, 110, 119, 141 Biotransformation, 17, 49, 141 Bladder, 142, 147, 160, 167, 174, 183 Blastomycosis, 142, 162 Blood Coagulation, 142, 143 Blood Glucose, 78, 142, 158, 161 Blood Platelets, 142, 178 Blood pressure, 6, 15, 48, 54, 69, 94, 138, 140, 142, 143, 144, 156, 160, 166, 168, 170, 178, 179 Blood vessel, 69, 87, 137, 140, 141, 142, 143, 144, 145, 152, 156, 170, 179, 180, 181, 183, 184

Body Fluids, 142, 143, 179 Bone Marrow, 13, 142, 149, 160, 164, 179 Bowel, 137, 142, 150, 162, 163, 169, 171, 180 Bowel Movement, 142, 150, 180 Brachial, 21, 142 Brachial Artery, 21, 142 Bradykinin, 142, 168 Branch, 131, 142, 152, 170, 175, 179, 181 Breakdown, 142, 150, 155, 179 Bronchi, 142, 153 Bronchitis, 91, 142 Buffers, 140, 142 Bypass, 59, 143 C Calcification, 139, 143 Calcium, 5, 87, 89, 143, 146, 150, 178 Calcium channel blocker, 89, 143 Candidiasis, 143, 155 Capillary, 11, 24, 142, 143, 156, 163, 184 Capsules, 143, 151, 156 Captopril, 62, 76, 77, 78, 89, 143 Carbohydrate, 78, 143, 148, 156, 157, 173 Carcinogenic, 143, 173, 180 Cardiac, 17, 20, 45, 47, 53, 84, 85, 88, 89, 109, 140, 141, 143, 148, 153, 167, 177, 180 Cardiac Output, 141, 143 Cardiomyopathy, 63, 143 Cardioselective, 140, 143, 173 Cardiovascular disease, 3, 9, 15, 25, 28, 38, 80, 81, 95, 97, 101, 108, 110, 144, 164 Carnitine, 79, 80, 144 Carotid Arteries, 63, 144 Case report, 15, 144 Catabolism, 13, 144 Catheter, 76, 144, 152 Catheterization, 137, 144 Cause of Death, 7, 85, 91, 144 Cell Death, 101, 139, 144, 156 Cell Division, 140, 144, 166, 172 Cell proliferation, 139, 144, 178 Cellobiose, 144 Cellulose, 75, 76, 80, 144, 155, 172 Central Nervous System, 6, 135, 140, 144, 155, 156, 157, 166, 167, 178 Central Nervous System Infections, 144, 157 Centrifugation, 144, 166 Cerebral, 8, 144, 145, 153, 175 Cerebrospinal, 22, 144, 145 Cerebrospinal fluid, 22, 145 Cerebrotendinous Xanthomatosis, 19, 145

Index

Cerebrovascular, 29, 95, 101, 144, 145 Cerebrum, 144, 145 Cervix, 145, 176 Character, 92, 137, 145, 149 Chemotaxis, 43, 145 Chenodeoxycholic Acid, 19, 145, 183 Chin, 145, 165 Chlorophyll, 145, 155 Choleretic, 145, 183 Cholestanol, 19, 145 Cholesterol Esters, 145, 163 Cholestyramine, 30, 41, 42, 54, 59, 62, 75, 84, 145 Chromatin, 139, 145, 153, 168 Chronic, 3, 4, 7, 10, 28, 46, 91, 142, 145, 150, 153, 161, 162, 170, 180, 183 Chronic Disease, 91, 145 Chronic renal, 3, 4, 28, 46, 145, 183 Chylomicrons, 145, 163 Cilazapril, 76, 146 Citrus, 139, 146 Clinical Medicine, 146, 173 Clinical trial, 5, 52, 53, 69, 70, 96, 119, 146, 148, 149, 151, 176 Cloning, 79, 141, 146 Coagulation, 142, 146, 158, 181, 184 Cognition, 6, 9, 146 Colestipol, 75, 146 Collagen, 136, 146, 172 Collateral Circulation, 47, 146 Colloidal, 136, 146, 151 Combination Therapy, 57, 87, 146 Complement, 146, 156, 165 Compliance, 5, 39, 57, 147 Computational Biology, 119, 147 Computed tomography, 49, 147 Computerized tomography, 147 Concomitant, 15, 78, 147 Congestive heart failure, 7, 146, 147, 164 Conjugated, 141, 145, 147, 149 Conjugation, 142, 147 Connective Tissue, 139, 142, 146, 147, 154, 155, 156, 164, 177, 181 Constipation, 95, 147, 178 Constriction, 148, 184 Constriction, Pathologic, 148, 184 Consumption, 5, 69, 148, 176 Contamination, 148, 158 Contractility, 137, 148 Contraindications, ii, 148 Control group, 8, 148 Conventional therapy, 148

189

Conventional treatment, 51, 148 Coordination, 148, 167 Cornea, 145, 148 Coronary Arteriosclerosis, 84, 148, 167 Coronary Circulation, 137, 148, 168 Coronary Disease, 4, 69, 86, 124, 148 Coronary heart disease, 5, 7, 17, 22, 28, 29, 40, 51, 52, 78, 80, 89, 96, 100, 144, 148, 159 Coronary Thrombosis, 148, 166, 167 Coronary Vessels, 148 Cortex, 148 Corticosteroid, 37, 148 Cranial, 149, 157 Craniocerebral Trauma, 149, 157 Crystallization, 93, 149 Curative, 149, 168, 181 Cyclic, 149, 157, 168, 174 Cyclosporine, 14, 149 Cytochrome, 8, 21, 74, 149 Cytokine, 37, 149, 181 Cytoplasm, 139, 141, 149, 153, 168 Cytotoxic, 58, 149, 178 D De novo, 86, 149 Degenerative, 101, 149, 158 Deletion, 139, 149 Density, 7, 27, 28, 32, 48, 51, 58, 62, 75, 77, 81, 138, 141, 144, 149, 151, 159, 163, 164, 169, 179 Depressive Disorder, 149, 164 Deuterium, 149, 159 Diabetes Insipidus, 150, 159 Diabetes Mellitus, 21, 28, 63, 78, 79, 91, 150, 157, 158 Diagnostic procedure, 73, 110, 150 Diarrhea, 145, 150 Diastolic, 150, 160 Dietary Fats, 150, 163 Digestion, 141, 142, 150, 162, 163, 164, 180 Digestive system, 71, 150 Digestive tract, 150, 179 Dihydrotestosterone, 150, 176 Dihydroxy, 85, 102, 150 Dilatation, 137, 150, 184 Dilatation, Pathologic, 150, 184 Dilation, 55, 142, 150, 184 Dilator, 150, 168 Diltiazem, 58, 150 Dimethyl, 85, 150 Direct, iii, 55, 64, 65, 82, 113, 146, 150, 151, 155, 176

190

Pravastatin

Discrete, 150, 181 Disposition, 6, 15, 17, 21, 26, 150 Dissociation, 136, 150, 162 Dopamine, 150, 166, 171 Dosage Forms, 93, 151 Dose-dependent, 26, 44, 151 Double-blind, 14, 31, 53, 151 Drug Interactions, 9, 10, 21, 114, 151 Drug Tolerance, 151, 182 Duodenum, 141, 151, 180 Dyes, 137, 141, 151, 168 Dyslipidemia, 53, 56, 64, 79, 97, 103, 151 Dysuria, 94, 151 E Edema, 151, 159, 167, 183 Efficacy, 13, 14, 18, 20, 22, 23, 31, 40, 46, 49, 52, 53, 54, 55, 63, 64, 80, 84, 151 Elasticity, 139, 148, 151 Elective, 53, 151 Electrocardiography, 30, 151 Electrolyte, 148, 151, 166, 173, 179, 183 Electrophoresis, 11, 151 Elementary Particles, 152, 165, 175 Emboli, 152, 184 Embolism, 152, 175, 184 Embolization, 152, 184 Embolus, 152, 160 Embryo, 152, 160 Emergency Medicine, 101, 152 Emergency Treatment, 152 Emphysema, 91, 152 Emulsions, 62, 136, 152 Enalapril, 15, 78, 152 Endarterectomy, 137, 152 Endogenous, 43, 150, 152, 168, 174 Endopeptidases, 152, 174 Endostatin, 87, 152 Endothelial cell, 7, 88, 152 Endothelium, 50, 63, 152, 153, 168, 172 Endothelium, Lymphatic, 152, 153 Endothelium, Vascular, 152, 153 Endothelium-derived, 153, 168 Endotoxic, 153, 163 Endotoxin, 153, 183 End-stage renal, 145, 153 Environmental Health, 118, 120, 153 Enzymatic, 97, 137, 143, 147, 153, 165 Eosinophils, 153, 163 Epidemiological, 80, 153 Epinephrine, 135, 151, 153, 168 Epithelial, 153, 158 Epithelial Cells, 153, 158

Epithelium, 152, 153 Erythrocyte Deformability, 35, 153 Erythrocytes, 64, 142, 153 Esophagus, 150, 153, 180 Esterification, 50, 153 Estradiol, 10, 153 Estrogen, 6, 12, 26, 154 Estrogen receptor, 6, 154 Ethanol, 154 Ethinyl Estradiol, 10, 154 Evacuation, 147, 154, 163 Excipient, 80, 154 Excitation, 10, 154 Exogenous, 141, 143, 152, 154, 174, 183 Extracellular, 7, 137, 140, 147, 154, 179 Extraction, 97, 154 F Fallopian tube, 154, 176 Family Planning, 119, 154 Fat, 69, 70, 91, 135, 139, 141, 142, 148, 152, 154, 156, 163, 167, 169, 177, 179, 182, 183 Fatigue, 154, 158 Fatty acids, 91, 136, 154, 163, 169, 174, 181 Feces, 145, 147, 154, 180 Femoral, 18, 154 Femoral Artery, 18, 154 Femur, 154 Fermentation, 81, 82, 83, 90, 92, 97, 98, 99, 154 Fibrin, 142, 154, 172, 181 Fibrinogen, 154, 172, 181 Fibrosis, 91, 154, 177 Flatus, 155 Flavoxate, 94, 155 Fluconazole, 10, 155 Fluoxetine, 10, 155 Foam Cells, 76, 88, 155, 185 Forearm, 69, 142, 155 Fosinopril, 76, 78, 155 Free Radicals, 10, 138, 150, 155 Freeze Drying, 98, 155 Fungi, 77, 86, 138, 140, 147, 155, 166, 185 Fungus, 77, 143, 155 G Gallbladder, 135, 141, 150, 155 Gallstones, 141, 145, 155, 158, 183 Ganglia, 135, 155, 168, 180 Gas, 24, 25, 155, 159, 168 Gastric, 140, 144, 151, 155 Gastrin, 155, 159 Gastrointestinal, 6, 32, 142, 153, 154, 156, 178, 180

Index

Gastrointestinal tract, 154, 156, 178, 180 Gemfibrozil, 8, 12, 33, 41, 53, 65, 75, 156 Gene, 8, 10, 74, 87, 136, 141, 156, 162 Genetic Code, 156, 169 Genetic Engineering, 74, 141, 146, 156 Genetic testing, 87, 156 Genotype, 27, 31, 42, 156 Giant Cells, 156, 177 Gland, 6, 135, 156, 160, 164, 165, 170, 172, 174, 178, 180, 182 Glioma, 47, 156 Glomerular, 4, 156, 162 Glomerular Filtration Rate, 4, 156 Glomerulus, 156 Glucocorticoids, 135, 148, 156 Glucose, 78, 138, 139, 142, 144, 150, 156, 157, 158, 161, 177 Glucose Intolerance, 78, 150, 156 Glucose tolerance, 78, 157 Glucose Tolerance Test, 157 Glutathione Peroxidase, 157, 178 Glycine, 136, 141, 145, 157 Glycoprotein, 6, 154, 156, 157, 171, 183 Gonad, 157 Gonadal, 30, 157, 180 Governing Board, 157, 173 Graft, 14, 157, 159 Gram-negative, 153, 157, 181 Gram-positive, 157, 181 Gram-Positive Bacteria, 157, 181 Granule, 37, 157 Growth, 18, 32, 36, 43, 48, 54, 87, 137, 138, 139, 144, 152, 157, 161, 166, 167, 169, 172, 183 Guanylate Cyclase, 157, 168 H Habitual, 145, 157 Haplotypes, 8, 157 Headache, 15, 157, 158, 178 Headache Disorders, 158 Heart attack, 70, 100, 144, 158 Heart failure, 10, 137, 158 Heart Transplantation, 22, 53, 58, 158 Heme, 149, 158 Hemoglobin, 153, 158 Hemorrhage, 149, 157, 158, 180 Hemostasis, 158, 178 Hepatic, 6, 8, 29, 37, 38, 96, 136, 157, 158, 179 Hepatitis, 14, 158 Hepatitis A, 14, 158 Hepatocytes, 34, 158

191

Hepatoma, 43, 158 Hepatovirus, 158 Heredity, 156, 158 Heterotrophic, 155, 158 High blood cholesterol, 86, 158 Histidine, 159, 161 Histology, 13, 159 Homogeneous, 99, 139, 159, 171 Homologous, 91, 136, 159 Hormonal, 149, 159 Hormone, 17, 37, 135, 148, 153, 155, 159, 161, 173, 177, 178, 179, 181 Host, 74, 140, 159, 160, 184 Hydrochlorothiazide, 62, 159 Hydrogen, 93, 135, 141, 143, 149, 157, 159, 166, 169, 171, 175 Hydrolysis, 95, 142, 144, 159, 163 Hydrophilic, 9, 159 Hydrophobic, 159, 163 Hydroxy Acids, 83, 159 Hydroxylation, 86, 97, 159 Hyperlipidaemia, 57, 64, 80, 159 Hyperlipidemia, 21, 29, 30, 35, 41, 43, 47, 48, 53, 57, 58, 63, 77, 82, 83, 94, 99, 151, 159 Hyperplasia, 6, 159 Hypersensitivity, 160, 177 Hyperthyroidism, 160, 174 Hypertriglyceridemia, 151, 160 Hypertrophy, 159, 160 Hypnotic, 140, 160, 181 Hypolipidemic, 25, 26, 31, 160 Hypotension, 39, 160 I Id, 65, 124, 130, 132, 160 Idiopathic, 160, 177 Iliac Artery, 154, 160 Immune response, 138, 140, 149, 160, 165, 180, 184 Immune system, 160, 164, 167, 184 Immunization, 160, 173 Immunogenic, 160, 163 Impairment, 55, 160, 165 In vitro, 6, 10, 43, 47, 58, 160 In vivo, 6, 9, 25, 58, 86, 160, 163 Incontinence, 94, 160, 169 Indicative, 105, 160, 170, 183 Induction, 7, 137, 160, 179 Infarction, 4, 5, 8, 23, 27, 36, 47, 51, 57, 64, 77, 81, 84, 93, 95, 96, 101, 148, 160, 166, 167, 174, 184

192

Pravastatin

Infection, 24, 70, 139, 141, 142, 143, 161, 164, 177, 180, 184 Ingestion, 157, 161 Inhalation, 135, 161 Inorganic, 90, 98, 161, 164 Inositol, 85, 86, 88, 103, 161 Inotropic, 140, 151, 161 Insight, 11, 161 Insomnia, 161, 178 Insulator, 161, 167 Insulin, 12, 13, 28, 40, 41, 63, 64, 77, 78, 83, 91, 94, 103, 157, 161, 177, 183 Insulin-dependent diabetes mellitus, 12, 13, 40, 79, 161 Interferon, 87, 161 Interferon Alfa-2b, 87, 161 Interferon-alpha, 161 Intermittent, 93, 161, 171 Intermittent Claudication, 93, 161 Internal Medicine, 3, 12, 15, 17, 25, 27, 30, 39, 41, 46, 57, 62, 64, 65, 162 Interstitial, 91, 162 Intestinal, 56, 145, 157, 162, 165 Intestine, 6, 141, 142, 162, 163 Intracellular, 7, 91, 92, 161, 162, 165, 168, 173, 174, 176, 178 Intracellular Membranes, 162, 165 Intravascular, 38, 58, 162 Intrinsic, 85, 136, 162 Inulin, 156, 162 Ion Exchange, 98, 144, 162 Ionization, 16, 24, 25, 162 Ions, 135, 141, 142, 145, 150, 151, 159, 162 Ischemic stroke, 109, 162 Isopropyl, 102, 162 Isosorbide, 7, 162 Itraconazole, 38, 55, 162 J Joint, 102, 162, 180 K Kb, 118, 162 Kidney Disease, 4, 71, 118, 136, 162 Kidney stone, 162, 183 Kinetics, 13, 62, 162 L Labile, 95, 146, 162 Large Intestine, 150, 162, 163, 176, 179 Latent, 163, 173 Laxative, 136, 145, 163, 164 Lens, 25, 44, 163 Lethal, 91, 163

Leukocytes, 76, 141, 142, 153, 161, 163, 168, 183 Library Services, 130, 163 Life cycle, 155, 163 Ligament, 154, 163, 174 Lipase, 8, 94, 163, 169 Lipid A, 17, 59, 163, 169 Lipid Peroxides, 88, 163 Lipolysis, 94, 163 Lipophilic, 9, 163 Lipopolysaccharides, 163 Lipoprotein Lipase, 87, 163 Lipoprotein(a), 39, 41, 164 Lisinopril, 15, 78, 164 Lithium, 82, 164 Liver Transplantation, 35, 164 Localized, 161, 164, 172 Low-density lipoprotein, 21, 27, 28, 32, 42, 46, 47, 50, 51, 53, 54, 58, 151, 163, 164 Lubricants, 80, 81, 82, 99, 164 Lymph, 140, 152, 153, 164, 177 Lymph node, 140, 164, 177 Lymphatic, 153, 161, 164, 179 Lymphocyte, 34, 58, 138, 164, 165 M Macrophage, 76, 164 Magnesium Hydroxide, 164 Magnesium Oxide, 80, 81, 164 Magnetic Resonance Imaging, 164, 165 Magnetic Resonance Spectroscopy, 9, 94, 165 Major Histocompatibility Complex, 157, 165 Malabsorption, 62, 165 Mammary, 6, 163, 165 Manic, 164, 165 Mannans, 155, 165 Mastitis, 165, 181 Meat, 84, 150, 165 Medial, 16, 139, 165 Mediator, 9, 69, 165, 178 Medicament, 75, 80, 165 MEDLINE, 119, 165 Melanin, 165, 171 Membrane, 31, 37, 140, 147, 150, 157, 165, 169, 171, 177, 178 Membrane Lipids, 31, 165, 171 Meninges, 144, 149, 165 Meningitis, 155, 162, 165 Menopause, 26, 43, 165, 173, 174 Mental, iv, 4, 71, 118, 120, 145, 146, 150, 154, 165, 173, 175, 183

Index

Mental Disorders, 71, 165, 173, 175 Mental Health, iv, 4, 71, 118, 120, 165, 173, 175 Metabolite, 16, 24, 94, 142, 146, 150, 155, 164, 165, 173 Methionine, 150, 166 MI, 4, 8, 110, 133, 166 Microbe, 166, 182 Microglia, 140, 166 Microorganism, 77, 100, 166, 184 Micro-organism, 74, 166 Microsomal, 8, 79, 166 Migration, 43, 166 Mineralocorticoids, 135, 148, 166 Mitosis, 139, 166 Modeling, 11, 166 Modification, 59, 63, 137, 156, 166, 175 Molecular, 31, 39, 91, 119, 121, 141, 147, 154, 163, 166, 172, 176, 180, 182, 183 Molecule, 82, 135, 138, 141, 146, 147, 150, 153, 154, 159, 166, 169, 176, 178, 182, 184 Monitor, 100, 166, 168 Monoamine, 94, 166 Monocyte, 76, 166 Mononuclear, 166, 183 Monotherapy, 13, 167 Morphological, 152, 155, 167 Motility, 167, 178 Multidrug resistance, 167, 171 Multiple sclerosis, 101, 167 Mydriatic, 150, 167 Myelin, 167 Myocardial Ischemia, 51, 137, 148, 167 Myocardium, 137, 166, 167 Myopathy, 9, 43, 75, 167 N Natriuresis, 137, 167 Nausea, 151, 167, 183 NCI, 1, 71, 117, 167 Need, 3, 89, 91, 96, 105, 125, 135, 145, 167, 182 Neomycin, 62, 167 Neoplasia, 6, 167 Nephropathy, 162, 167 Nephrosis, 167 Nephrotic, 16, 30, 48, 167 Nephrotic Syndrome, 30, 48, 167 Nerve, 10, 135, 145, 165, 167, 168, 170, 177, 180, 182, 184 Nervous System, 6, 85, 144, 165, 167, 168, 180 Neurotoxin, 101, 168

193

Neurotransmitters, 168, 178 Neutrophils, 43, 53, 163, 168 Niacin, 62, 66, 75, 101, 168, 183 Niceritrol, 57, 168 Nitric Oxide, 7, 10, 31, 101, 168 Nitrogen, 92, 137, 168, 183 Nitroglycerin, 7, 100, 101, 168 Norepinephrine, 135, 151, 168, 178 Normotensive, 77, 78, 89, 168 Nuclear, 94, 147, 168 Nuclei, 147, 156, 164, 165, 166, 168, 175 Nucleic acid, 87, 156, 168 Nucleus, 139, 141, 145, 149, 152, 153, 166, 168, 169, 175 O Ocular, 25, 44, 169 Ointments, 151, 169 Oleic Acids, 91, 169 Opacity, 149, 169 Organ Culture, 25, 169 Orlistat, 94, 169 Osmotic, 136, 162, 169 Osteogenic sarcoma, 169 Osteosarcoma, 19, 169 Outpatient, 27, 169 Ovaries, 169, 176 Ovary, 153, 157, 169 Oxidation, 36, 46, 135, 138, 142, 149, 157, 163, 169, 181 Oxidation-Reduction, 142, 169 Oxygenation, 34, 169 P Palliative, 170, 181 Pancreas, 15, 135, 150, 161, 163, 170 Pancreatic, 144, 170 Pancreatitis, 15, 170 Parotid, 170, 177 Paroxysmal, 137, 158, 170 Pathogenesis, 76, 78, 170 Pathologic, 139, 141, 148, 160, 170 Pathologic Processes, 139, 170 Pelvic, 170, 174 Penis, 170, 176 Peptide, 47, 136, 152, 170, 174, 175 Percutaneous, 47, 93, 170 Perfusion, 49, 170, 182 Peripheral blood, 43, 161, 170 Peripheral Vascular Disease, 81, 170 Peritoneal, 51, 170, 171 Peritoneal Cavity, 170, 171 Peritoneal Dialysis, 51, 171 Peritoneum, 170, 171

194

Pravastatin

Peroxide, 88, 157, 171 P-Glycoprotein, 8, 171 PH, 22, 44, 49, 58, 171 Pharmaceutical Preparations, 144, 154, 171 Pharmaceutical Solutions, 151, 171 Pharmacodynamics, 45, 57, 171 Pharmacokinetic, 9, 11, 14, 19, 39, 44, 171 Pharmacologic, 5, 171, 182 Phenylalanine, 53, 171 Phospholipids, 154, 161, 163, 165, 171 Phosphorus, 76, 143, 171 Phosphorylated, 146, 171 Physical Examination, 159, 171 Physiologic, 136, 162, 171, 174, 176, 178 Pilot study, 17, 45, 56, 171 Pituitary Gland, 148, 172 Placenta, 154, 172, 173 Plants, 146, 156, 162, 168, 172, 177, 182 Plaque, 28, 101, 108, 137, 172 Plasmin, 172 Plasminogen, 8, 172 Plasminogen Activators, 172 Platelet Activation, 51, 172, 178 Platelet Aggregation, 7, 37, 63, 88, 93, 101, 168, 172 Platelets, 64, 101, 168, 172, 181 Pneumonia, 148, 172 Pneumonitis, 91, 172 Polymerase, 172, 177 Polymers, 76, 172, 175 Polymorphic, 93, 172 Polymorphism, 8, 16, 173 Polysaccharide, 138, 144, 173 Postmenopausal, 12, 17, 26, 173 Postprandial, 19, 22, 173 Potassium, 94, 159, 166, 173 Potentiate, 7, 173 Practice Guidelines, 120, 173 Pravachol, 18, 32, 107, 108, 109, 114, 173 Precursor, 45, 77, 101, 139, 151, 153, 168, 171, 172, 173, 183 Predisposition, 87, 173 Pressoreceptors, 140, 173 Primary Prevention, 38, 44, 59, 173 Prodrug, 146, 155, 173 Progesterone, 173, 180 Progression, 38, 49, 51, 89, 96, 173 Progressive, 139, 145, 151, 157, 172, 173, 183 Promoter, 16, 74, 173 Prophylaxis, 84, 173, 184

Propranolol, 44, 140, 173 Prospective study, 56, 78, 174 Prostaglandin, 17, 137, 174 Prostaglandins A, 174 Prostate, 6, 174, 176 Prostate gland, 6, 174 Prostatic Hyperplasia, 6, 174 Protease, 10, 25, 46, 47, 146, 174 Protease Inhibitors, 10, 47, 174 Protein Binding, 174, 182 Protein C, 136, 138, 140, 163, 164, 174 Protein S, 141, 156, 167, 175 Proteins, 10, 54, 74, 91, 136, 137, 138, 145, 146, 153, 165, 166, 168, 170, 172, 174, 175, 176, 178 Proteinuria, 4, 28, 108, 167, 175 Protons, 159, 165, 175 Protozoa, 147, 166, 175 Psychiatric, 85, 165, 175 Psychiatry, 52, 56, 175 Psychic, 165, 175 Psychomotor, 9, 175 Public Health, 6, 120, 175 Public Policy, 119, 175 Pulmonary, 91, 142, 148, 175, 184 Pulmonary Artery, 142, 175, 184 Pulmonary Embolism, 175, 184 Pulse, 94, 166, 175 Pupil, 148, 150, 167, 175 Purifying, 92, 97, 98, 175 Q Quality of Life, 27, 33, 91, 175 R Race, 166, 175 Radiation, 137, 152, 155, 175, 185 Radioactive, 159, 162, 168, 175 Radiological, 170, 175 Randomized, 4, 6, 8, 14, 15, 16, 18, 23, 24, 25, 28, 31, 39, 42, 49, 53, 151, 176 Reactive Oxygen Species, 7, 176 Receptor, 26, 38, 42, 47, 48, 89, 93, 138, 151, 176, 178 Receptors, Serotonin, 176, 178 Recombinant, 74, 161, 176, 184 Recombinant Proteins, 74, 176 Rectum, 142, 150, 155, 160, 163, 174, 176 Recurrence, 89, 176 Refer, 1, 146, 155, 176, 182 Reflective, 6, 176 Refraction, 176, 179 Regimen, 10, 45, 80, 151, 176 Remission, 176

Index

Renin, 137, 143, 176 Renin-Angiotensin System, 137, 143, 176 Reproductive system, 6, 174, 176 Respiration, 166, 176, 177 Respiratory distress syndrome, 91, 177 Resuscitation, 152, 177 Retina, 163, 177 Reverse Transcriptase Inhibitors, 10, 177 Rhabdomyolysis, 9, 38, 52, 75, 177 Rheumatism, 177 Rheumatoid, 102, 177 Rheumatoid arthritis, 102, 177 Riboflavin, 103, 177 Risk factor, 7, 22, 52, 63, 78, 84, 85, 100, 103, 174, 177 Risk patient, 101, 177 Rod, 140, 177 Rosiglitazone, 94, 177 S Salivary, 150, 177 Salivary glands, 150, 177 Saponins, 177, 180 Sarcoidosis, 43, 177 Sclerosis, 139, 167, 177 Screening, 11, 146, 177 Secretion, 58, 149, 156, 161, 166, 178 Selenium, 87, 178 Semen, 174, 178 Semisynthetic, 154, 178 Sequencing, 8, 178 Serotonin, 9, 94, 155, 176, 178, 183 Serous, 152, 178 Shivering, 178, 181 Sibutramine, 94, 178 Side effect, 4, 5, 80, 83, 84, 94, 95, 102, 113, 135, 178, 182 Signal Transduction, 161, 178 Skeletal, 137, 177, 179 Skeleton, 154, 162, 174, 179 Small intestine, 6, 92, 96, 145, 151, 159, 162, 179 Smooth muscle, 44, 76, 94, 155, 168, 176, 179, 180 Social Environment, 175, 179 Sodium, 17, 18, 24, 26, 48, 74, 77, 80, 81, 93, 96, 97, 98, 105, 159, 166, 167, 179 Soft tissue, 142, 179 Solid tumor, 137, 152, 179 Solvent, 93, 98, 154, 169, 171, 179 Sound wave, 176, 179 Specialist, 125, 150, 179

195

Species, 76, 78, 79, 82, 83, 89, 92, 98, 99, 153, 166, 175, 176, 179, 180, 181, 182, 184 Specificity, 136, 152, 179, 182 Spectrum, 94, 166, 179 Spermatogenesis, 6, 62, 179 Spinal cord, 140, 142, 144, 145, 165, 168, 179, 180 Spleen, 164, 177, 179 Stabilization, 101, 180 Stent, 58, 180 Steroid, 30, 141, 158, 177, 178, 180 Stimulus, 148, 154, 180, 181 Stomach, 75, 96, 135, 140, 150, 153, 155, 156, 157, 159, 167, 170, 179, 180 Stool, 160, 163, 180 Stress, 167, 173, 177, 180 Stroke, 4, 7, 8, 48, 51, 52, 71, 81, 93, 101, 109, 110, 118, 124, 143, 144, 162, 180 Subacute, 161, 180 Subarachnoid, 157, 180 Subclinical, 161, 180 Subcutaneous, 135, 151, 180 Sublingual, 100, 180 Subspecies, 8, 179, 180 Substance P, 165, 178, 180 Substrate, 7, 74, 77, 180 Superoxide, 7, 53, 180 Suppression, 101, 149, 180 Sympathetic Nervous System, 137, 180 Symphysis, 145, 174, 180 Symptomatic, 4, 170, 180 Synergistic, 83, 101, 181 Systemic, 11, 91, 96, 114, 138, 142, 143, 153, 161, 177, 181, 183, 184 Systolic, 160, 181 T Taurine, 88, 141, 145, 181 Tendon, 19, 181 Teratogenic, 150, 181 Testicular, 6, 62, 181 Testis, 154, 181 Testosterone, 176, 181 Thalidomide, 87, 181 Thermogenesis, 94, 181 Thigh, 154, 181 Thiostrepton, 74, 181 Threshold, 160, 181 Thrombin, 154, 172, 174, 181 Thrombocytes, 172, 181 Thrombolytic, 172, 181 Thrombosis, 13, 55, 81, 175, 180, 181

196

Pravastatin

Thrombus, 93, 101, 148, 160, 162, 167, 172, 181, 184 Thyroxine, 136, 171, 182 Tissue Distribution, 9, 182 Tolerance, 7, 78, 135, 157, 182 Tomography, 147, 165, 182 Tone, 168, 182 Torsion, 160, 182 Toxic, iv, 44, 79, 80, 101, 147, 163, 178, 182 Toxicity, 9, 87, 151, 182 Toxicology, 120, 182 Toxin, 153, 182 Transcriptase, 177, 182 Transcutaneous, 34, 182 Transfection, 141, 182 Translation, 136, 167, 182 Transmitter, 135, 140, 151, 165, 168, 182 Transplantation, 14, 15, 16, 19, 21, 29, 34, 35, 45, 46, 48, 50, 53, 58, 145, 160, 165, 182 Trauma, 170, 182 Triglyceride, 8, 70, 79, 97, 103, 146, 160, 182 Troglitazone, 83, 183 Tryptophan, 146, 178, 183 Tumor Necrosis Factor, 102, 181, 183 Tumour, 183, 185 Type 2 diabetes, 29, 64, 183 U Unconscious, 160, 183 Uraemia, 170, 183 Urethra, 170, 174, 183 Uric, 78, 183 Urinary, 27, 155, 160, 183 Urine, 4, 24, 92, 94, 136, 142, 150, 160, 162, 167, 175, 177, 183 Ursodeoxycholic Acid, 29, 183

Uterus, 145, 169, 173, 176, 183 V Vagina, 143, 145, 176, 183 Vascular, 5, 7, 8, 13, 44, 46, 76, 88, 89, 100, 101, 141, 153, 158, 160, 161, 168, 172, 173, 181, 183 Vascular Resistance, 141, 183 Vasculitis, 170, 183 Vasoconstriction, 101, 153, 183 Vasodilation, 7, 101, 137, 184 Vasodilators, 168, 184 Vasomotor, 6, 184 Vector, 74, 184 Vein, 137, 168, 170, 184 Venous, 93, 168, 175, 184 Venous Thrombosis, 93, 184 Ventricle, 175, 181, 184 Ventricular, 17, 184 Venules, 142, 143, 153, 184 Vesicular, 166, 184 Veterinary Medicine, 119, 181, 184 Virulence, 182, 184 Virus, 140, 144, 156, 161, 172, 184 Vitamin A, 66, 161, 184 Vitreous, 163, 177, 184 Vitro, 6, 38, 184 Vivo, 7, 10, 184 W Warfarin, 57, 184 White blood cell, 138, 163, 164, 166, 184 Womb, 176, 183, 185 X Xanthoma, 44, 83, 84, 185 X-ray, 147, 168, 185 Y Yeasts, 74, 155, 185

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