GAMMA
HYDROXYBUTYRATE 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., 1960Gamma Hydroxybutyrate: 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: 0-497-00443-7 1. Gamma Hydroxybutyrate-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.
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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 gamma hydroxybutyrate. 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 GAMMA HYDROXYBUTYRATE .................................................................. 3 Overview........................................................................................................................................ 3 Federally Funded Research on Gamma Hydroxybutyrate ............................................................. 3 The National Library of Medicine: PubMed ................................................................................ 21 CHAPTER 2. NUTRITION AND GAMMA HYDROXYBUTYRATE ........................................................ 25 Overview...................................................................................................................................... 25 Finding Nutrition Studies on Gamma Hydroxybutyrate............................................................ 25 Federal Resources on Nutrition ................................................................................................... 26 Additional Web Resources ........................................................................................................... 26 CHAPTER 3. ALTERNATIVE MEDICINE AND GAMMA HYDROXYBUTYRATE .................................. 29 Overview...................................................................................................................................... 29 National Center for Complementary and Alternative Medicine.................................................. 29 Additional Web Resources ........................................................................................................... 32 General References ....................................................................................................................... 33 CHAPTER 4. DISSERTATIONS ON GAMMA HYDROXYBUTYRATE .................................................... 35 Overview...................................................................................................................................... 35 Dissertations on Gamma Hydroxybutyrate................................................................................. 35 Keeping Current .......................................................................................................................... 35 CHAPTER 5. PATENTS ON GAMMA HYDROXYBUTYRATE ............................................................... 37 Overview...................................................................................................................................... 37 Patent Applications on Gamma Hydroxybutyrate ...................................................................... 37 Keeping Current .......................................................................................................................... 39 CHAPTER 6. PERIODICALS AND NEWS ON GAMMA HYDROXYBUTYRATE..................................... 41 Overview...................................................................................................................................... 41 News Services and Press Releases................................................................................................ 41 Academic Periodicals covering Gamma Hydroxybutyrate .......................................................... 43 APPENDIX A. PHYSICIAN RESOURCES ............................................................................................ 47 Overview...................................................................................................................................... 47 NIH Guidelines............................................................................................................................ 47 NIH Databases............................................................................................................................. 49 Other Commercial Databases....................................................................................................... 51 APPENDIX B. PATIENT RESOURCES ................................................................................................. 53 Overview...................................................................................................................................... 53 Patient Guideline Sources............................................................................................................ 53 Finding Associations.................................................................................................................... 54 APPENDIX C. FINDING MEDICAL LIBRARIES .................................................................................. 57 Overview...................................................................................................................................... 57 Preparation................................................................................................................................... 57 Finding a Local Medical Library.................................................................................................. 57 Medical Libraries in the U.S. and Canada ................................................................................... 57 ONLINE GLOSSARIES.................................................................................................................. 63 Online Dictionary Directories ..................................................................................................... 63 GAMMA HYDROXYBUTYRATE DICTIONARY .................................................................... 65 INDEX ................................................................................................................................................ 93
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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 gamma hydroxybutyrate 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 gamma hydroxybutyrate, 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 gamma hydroxybutyrate, 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 gamma hydroxybutyrate. 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 gamma hydroxybutyrate, 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 gamma hydroxybutyrate. 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 GAMMA HYDROXYBUTYRATE Overview In this chapter, we will show you how to locate peer-reviewed references and studies on gamma hydroxybutyrate.
Federally Funded Research on Gamma Hydroxybutyrate The U.S. Government supports a variety of research studies relating to gamma hydroxybutyrate. 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 gamma hydroxybutyrate. 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 gamma hydroxybutyrate. The following is typical of the type of information found when searching the CRISP database for gamma hydroxybutyrate: •
Project Title: A 3-FACTOR MODEL OF DRUG EFFECTS ON OPERANT RESPONDING Principal Investigator & Institution: Gonzalez, Fernando A.; Professor of Biochemistry; Morris Brown College 643 Martin Luther King Dr Nw Atlanta, Ga 30314 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 31-MAR-2003
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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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Summary: (Applicant?s Abstract): Hermstein?s mathematical formulation of the matching law (1970) has been applied to data from operant conditioning procedures to disentangle the changes in responding attributable to drug-induced alterations in motivation from the changes attributable to drug-induced motor function impairment. The goal has been to develop an assay procedure and a classification system for the mode of behavioral action of drugs that have predictive value about the range of behavioral effects of drugs and their abuse potential. The behavioral procedure most often used in the studies is a Multiple Variable-Interval schedule (MultVI) consisting of five components that vary from 5 to 300 s. The generated response rate data are fitted by the single alternative equation of the matching law to obtain the value of the two parameters of the equation: k and rb. A common interpretation of k has been that it reflects, exclusively, the organism?s motor capacity to respond. The parameter rb is presumed to denote motivational factors. Results of studies conducted in our lab cast doubt on the above interpretation of the parameters. The same studies, however, confirm that k and rb are not affected by drugs in the same way, and that they may reveal different underlying actions of the drug. An alternative mathematical model, not burdened by theoretical implications of the matching law, is herein proposed. The model contains an additional parameter that reflects a third factor that underlies responding under operant procedures: stimulus control. Experiments will be conducted to test the validity of the proposed model by manipulating variables that affect (1) facility to respond, (2) reinforcer efficacy and (3) stimulus control. The effects of acute injections of d-amphetamine, gammahydroxybutyrate, morphine, diazepam and pimozide on the parameters of the model will be studied with rats trained to respond under a six-component MultVI schedule. The effects of chronic administration of the drugs and the development of tolerance or sensitization as denoted by the three parameters will also be investigated. The project will provide minority undergraduates with research experience by involving them in all phases of the study as Research Assistants. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BEHAVIORAL EFFECTS OF GHB IN HEALTHY VOLUNTEERS Principal Investigator & Institution: Oliveto Beaudoin, Alison; Psychiatry; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 09-JUL-2001; Project End 30-JUN-2004 Summary: (provided by applicant): Gamma-hydroxybutyric acid (GHB), an agent with sedative/muscle relaxant properties used therapeutically in other countries, has become increasingly popular as a recreational drug among young adults. Yet, despite increasing concern of its availability and potential for abuse in the United States, there is a paucity of research on the behavioral effects of GHB. Thus, of importance is to better characterize the behavioral pharmacology of GHB in humans. To this end, the major aim of this three-year application is to develop a GHB instructed novel-response drug discrimination procedure in humans, in order to examine the discriminative stimulus, self-reported performance and cardiovascular effects of GHB. In the instructed novelresponse drug discrimination procedure, subjects are trained to distinguish between a dose of GHB and placebo. Subsequently, the effects of various agents are examined to determine whether these agents produce effects similar to either training condition or neither condition (e.g., novel). This procedure allows for simultaneous assessment of objective behavioral measures such as discrimination, self-reports and physiological responses, providing a wide behavioral profile of effect. First, however, the training doses of GHB to be employed in the discrimination paradigm will be determined in
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study 1 by assessing the self-reported, physiological and performance effects of GHB across a wide range of doses. Self-reported, physiological, observer, and performance effects will be assessed prior to and several time points following drug administration. The results of study 1 will be used to determine peak and duration of GHB effects at each dose as well as a higher and lower dose of GHB that have discernable self-reported effects while producing minimal behavioral impairment to test as training drug stimuli in the drug discrimination procedure. A second study will then be conducted to examine the effects of GHB, the GABAb agonist baclofen, the benzodiazepine GABAa agonist triazolam, and the methylxanthine stimulant caffeine in humans trained to discriminate either a high or low dose of GHB from placebo under the instructed novelresponse discrimination procedure. The results of this study will shed light on the pharmacological specificity of the GHB stimulus at two different training doses as well as its relationship to self-reported, physiological and performance effects. This study will also potentially establish a standard methodology to characterize systematically the behavioral effects of GHB in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CLUB-DRUGS AND HIV RISK BEHAVIOR IN HIGH-RISK MEN Principal Investigator & Institution: Colfax, Grant N.; San Francisco Dept of Public Health 101 Grove St, Rm 308 San Francisco, Ca 94102 Timing: Fiscal Year 2003; Project Start 01-MAR-2003; Project End 28-FEB-2008 Summary: (provided by applicant): My goal is to become a leader in HIV prevention intervention research. K23 award support will allow me to develop the skills I need to become an independent researcher, with a focus on developing and implementing behavioral interventions to prevent HIV. I will acquire training in 1) behavioral science to better understand HIV risk behavior and theories about substance use; 2) qualitative research skills to perform formative research for intervention development; and 3) designing and implementing HIV prevention interventions by answering formative research questions and translating formative research data into a full-scale intervention. I will apply this new knowledge to the study of club-drug using men who have sex with men (MSM). While effective behavioral interventions have been developed for MSM and injection drug user (IDU) populations, less attention has been paid to club-drug use among MSM, and the relationship between club-drug use and high-risk sexual behavior. I hypothesize that 1) club drugs directly contribute to high-risk sexual behavior among MSM; 2) characterizing the size, stability, and sociodemographics of club-drug and sexual networks of MSM is critical in designing interventions to reduce club-drug associated sexual risk behavior; and 3) a network intervention is a feasible and potentially effective way to reduce sexual risk behavior associated with club-drug use. To address the current gaps in club-drug and sexual risk behavior research, the 3 specific aims of my research plan during the K award period are 1) to identify, through quantitative work, which types and combinations of club drugs are associated with high-risk sexual behavior, and to characterize MSM club-drug networks and the sexual networks of club-drug using MSM; 2) to conduct qualitative interviews and collect field observation notes among club-drug using MSM to examine the interpersonal and contextual factors associated with club-drug networks and environments, not measurable through quantitative research; and 3) using results from specific aims 1 and 2, to design and pilot the feasibility and acceptability of a club- drug network intervention to reduce sexual risk behavior associated with club-drug use. Results from these complementary specific aims will be used to secure R01 funding for a larger, phase
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Gamma Hydroxybutyrate
III randomized trial to determine the efficacy of a network-based club drug intervention to reduce high-risk HIV sexual behaviors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEPENDENCE POTENTIAL OF GHB, GBL AND 1,4-BD Principal Investigator & Institution: Weerts, Elise M.; Assistant Professor; Psychiatry and Behavioral Scis; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-AUG-2004 Summary: (provided by applicant) Gamma-hydroxybutyrate (GHB) is currently under investigation as a potential treatment for narcolepsy and alcohol dependence. Although GHB is currently classified as a Schedule I substance under the controlled substances act, illicit use of GHB, and its precursors gamma-butyrolactone (GBL) and 1,4butanediol (1,4-BD), is on the rise. The ability of GHB and its precursors to produce physical dependence has not been evaluated in controlled studies in humans or laboratory animals. The goal of the proposed research is to evaluate the physical dependence potential of GHB, GBL and 1,4-BD. Two specific aims are proposed: Aim 1 is to characterize the behavioral effects of GHB, GBL, 1,4-BD after acute and chronic intragastric drug administration in baboons. Aim 2 is to characterize physical dependence and the withdrawal syndrome for GHB and its precursors GBL and 1,4-BD in baboons. First, GHB, GBL and 1,4-BD will be administered alone and then in combination with the GHB antagonist NCS-382. Changes in food-maintained behavior, observed behaviors, and fine motor coordination, when compared to controls, will be evaluated. Next a high dose of GHB, GBL or 1,4-BD will be administered chronically via continuous i.g. infusion and changes in food-maintained behavior, observed behaviors, and fine motor coordination, when compared to vehicle control, will be evaluated. Then, the GHB antagonist NCS-382 will be administered to baboons that have been chronically treated with GHB, GBL or 1,4-BD. Evidence for a precipitated withdrawal syndrome will be determined based on changes in food-maintained behavior, observed behaviors, and fine motor coordination when compared those same behaviors recorded during the vehicle baseline and following administration of the antagonist alone. Finally, chronic treatment with GHB, GBL or 1,4-BD will be abruptly discontinued. The presence and time-course of a spontaneous withdrawal syndrome will be determined based on comparison with the same behavioral measures determined during a) the vehicle baseline condition and b) during the chronic drug dosing condition. The results of these studies will provide critical information on the behavioral pharmacology and physical dependence potential of GHB and its precursors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DRUG DISCRIMINATION AND TOLERANCE TO COMMONLY ABUSED DRUGS Principal Investigator & Institution: Stahl, Jeanne M.; Morris Brown College 643 Martin Luther King Dr Nw Atlanta, Ga 30314 Timing: Fiscal Year 2002 Summary: (Applicant?s Abstract): There are 10 aims for this project involving two different lines of research. We propose to do the following: (1) to investigate the effects of three levels of weight reduction (0 percent, 10 percent, and 20 percent) on rate of acquisition and asymptotic performance on a two-lever drug discrimination task with gamma-hydroxybutyrate (GHB) vs. saline; (2) To test the discriminative stimulus properties of GHB, gamma-butyrolactone (GBL), flunitrazepam (Rohypnol), and
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ethanol; (3) To investigate discriminative stimulus properties of GHB and GBL when given as mixtures with ethanol; (4) To partially replicate and extend preliminary results on the effect of reinforcer type on the development of tolerance to reinforcer magnitude; (5) To determine the extent to which reinforcement context affects the development and degree of tolerance to amphetamine and morphine; (6) To determine the extent to which reinforcer magnitude affects the development and degree of tolerance to amphetamine and morphine; (7) To elucidate the role of behavioral variables in modulating the behavioral effects of drugs and to highlight their potential for the treatment of drug abuse; (8) To write a comprehensive review of the literature on the status of the concept of state dependent learning (SDL) vs. drug discrimination, to seek feedback from the few existing SDL researchers, and publish in a review journal; (9) To design experiments to partially replicate and extend our research with the Maier 3-table reasoning problem to determine whether rats that demonstrate a performance deficit when experiences are given under morphine and saline demonstrate similar deficits when tested with combinations of methadone and saline or buprenorphine and & saline; and (10) To expose high school, undergraduate, and graduate minority students to a variety of research methods used in behavioral pharmacology in order to prepare them for admission to and retention in excellent graduate research programs and, potentially, drug abuse research careers. Students will be involved in every aspect of this research including research ethics, animal care and handling, animal behavioral testing, data analysis, library research, literature review, and preparation of papers for presentation and publication. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ELECTROPHYSIOLOGICAL ACTION OF GHB IN BRAIN REWARD AREAS Principal Investigator & Institution: Crunelli, Vincenzo; Cardiff University Pob 921 Cardiff, Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-JUL-2004 Summary: (provided by applicant) Gamma-hydroxybutyric acid (GHB) is an endogenous brain substance that in recent years has become more and more popular as an illicit recreational drug for the euphoric sensation that it produces, despite the serious side effects and the potential for dependence that are associated with its intake. The goal of this proposal is to characterize the electrophysiological actions of GHB in the ventral tegmental area and nucleus accumbens, two key areas of the brain reward system, as only very limited electrophysiological data is available on GHB effects in these brain regions. To achieve this goal, the following in vitro investigations will be carried out in projection neurones and interneurones of these two areas using patch electrode recordings: i) analysis of GHB effects on intrinsic voltage-dependent Na+, K+ and Ca2+ currents, and ii) analysis of GHB action on excitatory and inhibitory synaptic currents originating from extrinsic and intrinsic afferents, and their long term potentiation/depression, where present. Using carefully selected combinations of available pharmacological tools, particular attention will be devoted to identify whether GHB and/or GABAB receptors are involved in each of the observed GHB effects, as behavioural, biochemical and electrophysiological evidence in other brain areas suggest an involvement of both receptors in the pharmacological actions of GHB. By characterizing the changes in membrane currents in neurones of the nucleus accumbens and ventral tegmental area following exposure to GHB, and by identifying the location and nature of the receptors involved, this study will provide the basic information necessary to understand GHB-elicited modifications in neuronal excitability in two key
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Gamma Hydroxybutyrate
areas of the brain reward system, and thus would, for the first time, allow us to draw a detailed picture of the cellular mechanisms underlying the action of this potential drug of abuse. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ENZYME & RECEPTOR ANTAGONISTS OF GHB, GBL & 1, 4-BD Principal Investigator & Institution: Quang, Lawrence S.; Adjunct Associate Professor of Pharmacol; None; Mass College of Pharm & Allied Hlth Scis and Allied Health Sciences Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 10-MAR-2002; Project End 28-FEB-2004 Summary: (provided by applicant) The widespread abuse of gamma-hydroxybutyrate (GHB) and its chemical precursors, gamma-butyrolactone (GBL) and 1,4-butanediol (1,4BD), has resulted in escalating episodes of life-threatening acute overdoses. Because abuse of GHB and its precursors is a recently evolving phenomenon, treatment strategies for acute overdoses are currently limited. The objectives of this proposal are to address two specific research areas solicited in the request for application (DA-01-014, "Research on GHB and Its Precursors") issued by the National Institute on Drug Abuse (NIDA): 1.) overdose and toxicity of GHB and its precursors, and 2.) treatment strategies for GHB and its precursors. Although GHB and GBL were made illegal by the Hillary J. Farias and Samantha Reed Date Rape Prohibition Act of 2000 (the former is now a federal schedule I drug, and the latter is a federal list I chemical), 1,4-BD is currently recognized as a Class I Health Hazard (a potentially life-threatening hazard). This designation imposes no legal restrictions on the manufacture, distribution (in dietary supplements), or possession of 1,4-BD. Increasingly, 1,4-BD has been responsible for severe life-threatening overdoses and deaths. Thus, our laboratory has prioritized and focused its research efforts on 1,4-BD, which is currently the only legally available GHBrelated drug. Additionally, 1,4-BD is the only GHB-related drug that can directly interact with ETOH, the most commonly coingested substance with GHB-related drugs, leading to dangerous interactions. Furthermore, its complete biotransformation to GHB permitted us the unique opportunity to study indirectly GHB's interactions with ETOH and GABA-B and GHB receptors. This application has three specific research aims. The first aim is to characterize 1,4-BD and GHB toxicity after acute overdoses. The second aim is to study potential interactions of 1,4-BD and GHB with ETOH. The third aim is to investigate potential antidotes for acute 1,4-BD overdose and combined acute 1,4-BD and ETOH overdose. Potentially effective antidotes exist for 1,4-BD, specifically, and for GHB, GBL, and 1,4-BD collectively. The antidote for 1,4-BD specifically is an enzyme antagonist of alcohol dehydrogenase (4-methylpyrazole, Antizol), which may block in vivo enzymatic biotransformation of 1,4-BD to GHB. The antidotes for the GHB, GBL, and 1,4-BD collectively are receptor antagonists of GABA-B receptors (CGP-35348) and GHB-specific receptors (NCS-382), the sites of pharmacologic action of GHB, GBL, and 1,4-BD. In general, a murine model (CD-l mice) will be used to assess the acute effects of 1,4-BD, GHB, and ETOH on behavioral (open field locomotion test), neuromuscular (righting reflex, rotarod test, grip strength test), and biochemical processes (blood 1,4BD and GHB levels). This murine model will also be used to study the effects of potential therapeutic agents for acute overdoses. The results of this study will expand upon promising data from pilot studies performed in this laboratory on acute 1,4-BD and GHB toxicity as well as novel therapeutic agents for its potential medical management. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GHB ABUSE: CHEMISTRY AND NEUROBIOLOGY Principal Investigator & Institution: France, Charles P.; Professor; Pharmacology; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229 Timing: Fiscal Year 2002; Project Start 26-SEP-2001; Project End 31-JUL-2004 Summary: Gamma-Hydroxybutyric acid (GHB) occurs endogenously in the brain where it is thought to be a neurotransmitter. GHB is used clinically for treating alcoholism and narcolepsy and is used non-medicinally, both as a primary drug of abuse (presumably because of its sedative/hypnotic effects) and as a sedating agent in unsuspecting victims (e.g., "date rate drug"). Despite GHB having been described more than 30 years ago and despite its widespread use, both medicinally and non-medicinally, relatively little is known about the mechanism that mediates the various effects of GHB. A GHBassociated binding site has been reported, although it is not known whether this site mediates the abuse- related effects of GHB. The paucity of information on the mechanism(s) of action of GHB results from a very limited set of relevant compounds that are available for studying this neurobiologic system and the absence of pharmacologically selective and validated neurochemical and behavioral procedures for characterizing the effects of GHB and related compounds. To that end, the studies proposed in this application will first characterize the receptor binding and behavioral effects of GHB and related compounds. Second, these studies will design and synthesize new compounds for studying the pharmacology of GHB. The working hypothesis of these multidisciplinary studies is that the behavioral effects of GHB are due to its actions on specific sites in brain that are not related to either GABAA or GABAB receptors. Studies under Specific Aim I will design and synthesize potent and selective agonists and antagonists for GHB receptors. Specific Aim II will characterize the binding of GHB and other compounds, including compounds that are synthesized under Specific Aim I, to specific sites in rat brain that have been characterized by our group with [3H]NCS382. The functional consequences of GHB binding will be examined under Specific Aim III, including a characterization of the effects of GHB and other compounds on schedulecontrolled behavior and an evaluation of discriminative stimulus effects of GHB. These systematic characterizations of the binding and behavioral effects of GHB and the development of newly-synthesized compounds for GHB receptors will provide important new information regarding the mechanisms that mediate effects of GHB and related compounds. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GHB ABUSE: MOTIVATIONS, MEDICAL CONSEQUENCES, & RISKS Principal Investigator & Institution: Dyer, Jo E.; Clinical Pharmacy; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 25-MAY-2002; Project End 30-APR-2007 Summary: BACKGROUND: Gamma hydroxybutyrate (GHB) and its precursors (GHBP) are major causes of drug-related coma in the U.S. Dramatic and rapid changes in patterns of GHB use are associated with increasing morbidity and mortality. Despite this, little is known about the determinants of adverse outcomes following use. STUDY HYPOTHESIS: Adverse outcomes following GHB use are multi- factorial. We propose to delineate the role of psychosocial and physical factors as predictors of adverse outcomes in GHB use; including socio-demographic factors, attitudinal issues, specific exposures (GHB v. GHB-P), and pharmaco-dynamics. EXPERIMENTAL PLAN: Component C1: California Poison Control System (CPCS) surveillance will capture
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Gamma Hydroxybutyrate
demographics, exposure, and outcomes for 600 exposure subjects over the study period. Product and blood/urine testing will confirm GHB or its precursors. Component C2: Structured interviews of 390 exposed subjects, recruited from the CPCS surveillance cohort, will collect supplemental data not available from passive surveillance alone. Component C3: Controlled human exposures in 144 volunteers will compare disposition kinetics and effects of GHB and 1,4 butanediol, examining dose-dependence, gender differences, ethnic differences, genetic influences and interaction with ethanol. Component C4: Focus groups will explore the motivating factors for GHB use and abuse. Nine focus groups (54 subjects) from 3 sources (an adverse experience group from C2; experimentally exposed subjects from C3; and a community-based sample of GHB users without adverse events) will evaluate differences in hazard perception, acquisition, settings and use outcomes. Analyse s: Multivariate modeling will have sufficient power to detect RR's less than 2.0 for key risk factors and outcomes in the 20 percent incidence range. Human exposures will use paired and repeated-measures comparisons with power to detect change slightly greater than one standard deviation. SIGNIFICANCE: This study, by elucidating predictors of adverse outcomes from GHB use will provide data important for clinical and public health interventions to reduce morbidity associated with this drug of abuse. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GHB EFFECTS ON EXTRACELLULAR DOPAMINE Principal Investigator & Institution: Walker, David; Pharmacology and Cancer Biology; Duke University Durham, Nc 27710 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Illicit use of gamma-Hydroxy butyrate (GHB), a popular new "club drug," has reached mini-epidemic levels in America. GHB is also in clinical trials for treatment of narcolepsy and alcohol addiction. GHB is pharmacologically unique among drugs of abuse because it is a naturally occurring substance in mammalian brain with its own receptor(s) and uptake system. Although reports of GHB abuse are rising rapidly, information about the interactions of GHB with the central dopamine systems that mediate drug reward and craving is conflicting. The purpose of the present proposal is to determine the effect of GHB on extracellular dopamine concentrations in awake rats using fast scan cyclic voltammetry. We will: (1) Determine dose- response relationships for the effects of GHB on electrically-stimulated dopamine concentrations in the caudate and the shell of the nucleus accumbens and resolve its effects on dopamine release and uptake kinetics, (2) Determine if repeated GHB exposure modifies the regulatory mechanisms that govern extracellular dopamine concentrations and alters the acute response to GHB. This research will study five doses of GHB that reflect human doses ranging from therapeutics to abuse. I hypothesize that low doses of GHB will increase dopamine release slightly in the caudate and nucleus accumbens and that high doses will robustly elevate dopamine release in both regions. These studies will utilize gastric administration of GHB in awake rats to provide realistic information about GHB effects on central dopamine neurotransmission Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GHB TOLERANCE AND DEPENDENCE Principal Investigator & Institution: Kuhn, Cynthia M.; Professor; Pharmacology and Cancer Biology; Duke University Durham, Nc 27710 Timing: Fiscal Year 2003; Project Start 20-SEP-2003; Project End 31-MAY-2007
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Summary: (provided by applicant): The purpose of this proposal is to investigate mechanisms of Gamma hydroxy butyrate (GHB) tolerance and dependence after chronic administration of low and high doses of GHB to rats. GHB is a novel sedative-hypnotic that is an emerging drug of abuse. GHB activates GHB, GABA-B and possibly GABA-A receptors, with a unique dose response relationship for each. When recreational users escalate use, tolerance develops and a withdrawal syndrome can occur that is characterized by insomnia, anxiety, and hallucinations. Tolerance and dependence to GHB are poorly characterized in animal models. We hypothesize that tolerance is related to dose and duration of exposure. We also hypothesize that the different receptor populations adapt at varying rates. We postulate that chronic treatment with lower doses or shorter regimens will cause tolerance at GHB and perhaps GABA-B receptors, while higher doses and longer treatments will lead to marked tolerance to GHB, GABA-A and GABA-B receptors. We will assess tolerance to GHB effects on sleep time, tilt plane and plus maze performance after chronic treatment with low or high doses for 7, 14 or 21 days. We will assess spontaneous and GHB (NCS-382) and GABA-B (CGP46381) antagonist-precipitated withdrawal by measuring sleep-wake cycle, locomotion as well as blood pressure and heart rate. Cross-tolerance to GABA-B (baclofen) and GABA-A (pentobarbital, diazepam) agonists will be assessed with the same behavioral measures. We will characterize inhibitory GHB mechanisms using electrophysiologic techniques in frontal cortex. GHB effects on spontaneous, evoked and mini GABA-A IPSCs and on postsynaptic potassium conductance will be determined. The effects of low and high GHB concentrations will be contrasted, and blockade by NCS-382 and CGP46381 on all parameters will be determined. Tolerance to specific GHB and GABA-B mechanisms will be studied by evaluating the same parameters in frontal cortex slices from animals treated chronically with low or high dose GHB. Finally, we will assess GHB effects on GABA-A receptors in naive and tolerant animals by measuring effects on GABA-mediated C1 uptake into synaptoneurosomes and its modulation by benzodiazepines, barbiturates and neurosteroids. These experiments should ultimately lead to the development of more effective pharmacotherapies for GHB dependence, which is an emerging drug abuse problem. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GHB: DISCRIMINATION AND EFFECTS ON LEARNING Principal Investigator & Institution: Baker, Lisa E.; Associate Professor; Psychology; Western Michigan University 1903 W Michigan Ave Kalamazoo, Mi 49008 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-AUG-2004 Summary: (provided by applicant) Gamma-hydroxybutyrate (GHB) abuse is a growing medical and social concern. Media attention has recently focused on the rampant recreational use of this substance among America's youth, and its notorious involvement in numerous drug-facilitated sexual assaults. The precursors of GHB (GBL and 1,4-BD) are found in some industrial solvents and also present a potential health hazard because their supply is not easily controlled. Despite the fact that GHB has been used for medicinal purposes in Europe for nearly 30 years and was available over-thecounter in the U.S. until 1990, the neurobehavioral consequences of GHB abuse are not well understood. Research on the neurochemical mechanisms underlying GHB's behavioral and subjective effects is imperative to understanding the abuse potential of this drug and ultimately to developing treatments for GHB abuse. Preclinical studies that assess these mechanisms are an essential component of this research. One objective of this proposal is to characterize further the neuropharmacological mediation of GHB's discriminative stimulus effects. This will be accomplished using both two-choice and
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Gamma Hydroxybutyrate
three-choice drug discrimination techniques in rats. Because other researchers have had some difficulty maintaining adequate stimulus control with GHB, methodological parameters will be experimentally assessed to determine the optimal conditions for establishing and maintaining GHB discrimination. Additionally, because very little is known about GHB's effects on learning and performance in preclinical models, a second objective is to investigate the effects of GHB in several behavioral assays that involve operant conditioning in rats. The acute and chronic effects of GHB will be examined in rats: (a) responding a multiple schedule during 10-hr sessions; (b) initially acquiring lever-press responding with immediate and delayed reinforcement; (c) performing a conditional discrimination under a fixed-consecutive number (FCN) schedule with and without an external discriminative stimulus; (d) performing a delayed conditional discrimination (DCD); and (e) performing under a multiple schedule of reinforcement with punishment in one component. Behavior under these assays is sensitive to other abused drugs. Therefore, these assays may be of value in characterizing the effects of GHB. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GHB: EFFECTS, WITHDRAWAL AND TREATMENT Principal Investigator & Institution: Miotto, Karen A.; Associate Clinical Professor; None; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Career Goals: The candidate is a psychiatrist whose goal is to expand her research and academic activities in the field of addiction medicine. Her immediate career goal is to obtain the training and experience necessary for becoming an independent investigator. Her professional goal is to become an academic resource in the field of addiction with a focus on evaluation of medications. Research Career Development Plan: The candidate proposes to obtain a Master of Science (M.S.) in Clinical Research Design and Statistical Analysis (CRDSA) from the University of Michigan School of Public Health. This program is designed specifically for physicians and other health care professionals involved in clinical research. In addition to this coursework, the applicant's career development plan draws on the resources of a large, well established addiction research group, the Integrated Substance Abuse Program (ISAP) at UCLA, and includes a program of supervision by experts in their respective fields in the qualitative and quantitative aspects of study design and methodology. Description of the research projects: The proposed research plan is designed to objectively describe signs and symptoms of GHB withdrawal, identify predictors of withdrawal severity and treatment response, and develop and validate treatment guidelines for GHB withdrawal. There has been a sharp rise in the number of GHB related emergency room visits in the United States over the past few years, yet little is known about effective treatment of GHB withdrawal and dependence. The signs and symptoms of GHB withdrawal begin one to six hours after last use, and may escalate rapidly and unpredictably to delirium, agitation, and psychosis. Given the rapid, progressive and serious nature of GHB withdrawal symptoms, there is a crucial need to develop improved treatments. There has been little systematic study of the signs and symptoms of withdrawal, and controlled studies on the effectiveness of treatment of these symptoms are lacking. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GHB: SYMPATHOMIMETIC ACTIONS OF A CNS DEPRESSANT Principal Investigator & Institution: Hicks, Alissa R.; Pharmacology; Louisiana State Univ Hsc New Orleans New Orleans, La 70112 Timing: Fiscal Year 2004; Project Start 02-FEB-2004; Project End 01-FEB-2006 Summary: (provided by applicant): Although typically thought of as a CNS depressant, our data along with that of others show that GHB has significant sympathomimetic cardiovascular properties. The mechanisms mediating the cardiovascular responses elicited by GHB are largely unknown. This lack of knowledge is significant given the increasing recreational use of GHB and the recent interest in its therapeutic use. The proposed studies employ a variety of techniques including radio telemetry, conscious nerve recording and state-of-the-art signal analysis techniques such as coherence analysis to characterize the cardiovascular responses elicited by GHB in conscious rats. Acute studies will 1) characterize the mean arterial pressure and heart rate responses elicited by the i.v. administration of GHB 2) determine the role of GHB and GABAb receptors in mediating the cardiovascular responses elicited by GHB and, 3) assess the potential for GHB to increase sympathetic outflow by activating forebrain sympathetic pathways. Chronic studies will, for the first time, characterize the cardiovascular responses elicited by the chronic administration of GHB and assess its potential to produce cardiac toxicity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HUMAN BEHAVORIAL PHARMACOLOGY OF GHB Principal Investigator & Institution: Roll, John M.; Assistant Director of Substance Abuse &; None; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-AUG-2004 Summary: (provided by applicant) Gamma-hydoxybutyrate (GHB) is a compound with a mixed reputation. On one hand it has been used quite successfully to treat persons suffering from narcolepsy and appears to be promising in the treatment of alcohol and opiate withdrawal. Furthermore it has been investigated as a treatment for schizophrenia, cocaine abuse, Parkinson's disease and night eating syndrome. On the other hand, GHB has been abused, presumably for its' psychoactive effects, with disastrous consequences including the development of a severe withdrawal syndrome, coma and even death. GHB has also been used to facilitate the commission of sexual assaults by surreptitiously providing it to the victim. Several investigators have suggested that GHB is a reinforcer with abuse potential while others have suggested exactly the opposite. Despite this wide-ranging history, the behavioral pharmacology of GHB has not been thoroughly examined. We are proposing a rigorous, inpatient double blind, placebo controlled, experimental procedure for assessing the physiological consequences, subjective properties, relative reinforcing potential, direct effects and pharmacokinetics of GHB in a group of regular GHB users. Furthermore, we are proposing to assess the degree to which GHB will be self-administered by volunteers. We believe that the successful completion of the proposed study will provide us with much needed data about the human behavioral pharmacological profile of GHB in the GHB user. We believe the data collected in the proposed study will be useful in developing effective treatments for those who have overdosed on GHB, for those who are in withdrawal from GHB, and for those who are attempting to quit using GHB. Furthermore, it is our belief that securing a fuller understanding of this interesting compound may help explain why it has come to be abused by certain individuals. This
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Gamma Hydroxybutyrate
last point may be of particular importance as it is likely that other drugs, with profiles similar to that of GHB, will enter the "Club Drug" milieu in the future and we may be able to inform policy surrounding these future agents based on a fuller understanding of GHB. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: KETOGENIC DIET AND BRAIN AMINO ACID METABOLISM Principal Investigator & Institution: Yudkoff, Marc; Professor; Children's Hospital of Philadelphia 34Th St and Civic Ctr Blvd Philadelphia, Pa 191044399 Timing: Fiscal Year 2002; Project Start 01-JUN-1998; Project End 31-MAY-2004 Summary: (from applicant's abstract) The ketogenic diet is often used to control seizures in children who are resistant to antiepileptic drugs. The mode of action is totally unknown. The PI hypothesizes, based on their preliminary data, that one reason the ketone bodies (3-OH-butyrate and acetoacetate) are so effective in controlling seizures is that they increase the brain concentration of GABA (gamma amino butyric acid), a major inhibitory neurotransmitter, and lower the concentration of aspartate, an excitatory compound. Ketone bodies bring about these changes because they sharply reduce the rate of transamination of glutamate to aspartate. As a result, more glutamate becomes available for the synthesis of GABA. In astrocytes, more glutamate becomes available to the glutamine synthetase pathway. This results in increased synthesis of glutamine, a highly effective precursor to GABA. They propose to test this hypothesis by developing a rat model of the ketogenic diet. The model involves the prolonged (from weeks to months) feeding of rat pups with either an artificial rat milk or an isocaloric amount of a high fat (ketogenic diet). They will use stable isotopes, e.g., 15N and 13C to measure rates of glutamate metabolism to GABA, aspartate and glutamine. Mass spectrometry is used as an analytical tool with which to measure stable isotopic abundance in amino acids and tricarboxylic acid cycle intermediates. The three specific aims are: (1) To test the above hypothesis; (2) To characterize the ketogenic diet: Is high fat feeding necessary, or could ketone bodies alone be fed? How rapidly do amino acid changes develop? How sustained are they? Are changes more pronounced in less mature animals?; and (3) To determine whether the ketogenic diet can ameliorate seizures in a standard rat model of epilepsy, and whether this therapeutic effect is associated with changes of amino acid levels that mimic those noted in control animals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MEASURING AND MODIFYING ETHANOL'S REINFORCING EFFECTS Principal Investigator & Institution: Winger, Gail D.; Research Professor; Pharmacology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2007 Summary: (provided by applicant): In rhesus monkeys, the reinforcing effects of intravenously delivered ethanol lead to high ethanol intake, high ethanol blood levels, marked intoxication, and, under continuous access conditions, "binge" patterns of ethanol consumption, physiological dependence, and withdrawal signs. These are some of the characteristics of severe human alcoholism, a condition that is likely to result, at least in part, from this pharmacologically based reinforcing effect of ethanol. We suggest that response-contingent delivery of i.v. ethanol is a fairly "pure" measure of these reinforcing effects of ethanol, relatively unmodified by the aspects of taste, fluid volume,
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and gastrointestinal absorption that appear to prevent consumption by monkeys of equally large amounts of ethanol by the oral route. We propose to use behavioral economic procedures (demand curves) to quantify these reinforcing effects of i.v. ethanol and to compare them with those of other intravenously delivered drugs. In further studies, these procedures will be used to determine how the combination of ethanol and other drugs of abuse changes the reinforcing effects of both drugs. Because demand functions are unaltered by changes in drug potency, but are modified by changes in drug effectiveness, the measurements should indicate whether the various drug combinations result in a greater reinforcing effectiveness than either drug alone, or whether the potencies of the drugs as reinforcers are enhanced when they are combined. Finally, this same analysis will be used to determine how the treatment drugs of naltrexone and acamprosate modify the reinforcing effects of intravenous ethanol, again either by decreasing its reinforcing effectiveness or by decreasing its potency as a reinforcer. These studies will provide information not currently available on how ethanol compares with other drugs in terms of its reinforcing effectiveness, information that could impact policy decisions regarding legalization or decriminalization of other drugs of abuse. Data relevant to the behavioral and pharmacological mechanisms underlying polydrug abuse involving ethanol, and underlying pharmacological treatment of alcoholism will also be obtained. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISMS OF SIGNAL TRANSDUCTION OF GHB ACTION Principal Investigator & Institution: Tunnicliff, Godfrey; Biochem and Molecular Biology; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-AUG-2004 Summary: (provided by applicant) Gamma-hydroxybutyrate (GHB) has gradually gained a foothold as a substance of abuse in the U.S. and has a reputation as being used as a "date-rape" drug, particularly in the presence of alcohol. Increasingly, incidents of untoward reactions and even death have been reported with GHB misuse. Administration of this drug results in a marked central nervous system (CNS) depressant action manifested by sedation and coma at higher doses. These effects can be accompanied by seizures, particularly in experimental animals. Owing to its pronounced CNS actions and to the fact that it is an endogenous brain substance, GHB is considered to be a neurotransmitter or a substance with a significant role in regulating neuronal function. Part of GHB action appears intimately tied to the GABAergic system. For this cross-disciplinary pilot project we propose to study the process of GHB signal transduction in both cultured neurons and animal nervous tissue. In Aim 1, we plan to use neuroblastoma hybrid NCB-20 cultures to investigate the effects of GHB on forskolin-induced cAMP production and the ability of GHB to activate pertussis toxin sensitive G-proteins. These studies are expected to lead to the identification of a subfamily of G-proteins associated with the GHB receptor. In Aim 2, this GHB receptorexpressing cell line will be used to study the involvement of plasma membrane Ca2+ regulatory mechanisms (calcium channels, sodium-calcium exchanger, Ca2+ pump, passive Ca2+ permeability) in GHB signal transduction. For Aim 3, we will map the regional distribution of GHB transport sites in the brain and ascertain the kinetic specificity of the GHB transporter for its substrate. Finally in Aim 4, based on the hypothesis that GHB activity at the GABAA receptors is dependent on their subunit composition, we will study the effects of GHB on GABA-stimulated chloride influx in different brain areas and in cultured cells expressing GABAA receptors composed of
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Gamma Hydroxybutyrate
different subunits. These studies may reveal the GABAA receptor subtype specificity for the effects of GHB and possibly new targets for drugs to treat GHB dependence and toxicity. The exploratory, four-pronged approach of this project promises to expand our current, limited understanding of how GHB functions as a neuronal regulatory chemical and how its pharmacological effects are linked to cellular events. In turn, this will help to develop therapeutic and preventive strategies resulting in a lessened abuse potential of GHB. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INTOXICATION.
MECHANISMS/GHB/MODELS/ACUTE/CHRONIC
GBH
Principal Investigator & Institution: Mody, Istvan; Professor; Neurology; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-JUL-2006 Summary: Gamma-hydroxybutyrate is abused by humans occasionally or chronically due to its euphoric and sedative effects. An overdose of GHB can lead to a severe depression of the consciousness, seizures, vomiting and even death, while long-term abuse can be associated with a marked withdrawal syndrome. Thus, ingestion of GHB causes biological changes in the brain that may have major influence on the well-being of the individual. The goal of this proposal is to characterize specific alterations in the brain in a mouse model of GHB abuse. The fundamental hypothesis to be tested by the present proposal is that chronic GHB administration affects the mammalian brain through GHB effects via GABAB receptors. This causes behavioral alterations attributable to changes in physiological processes, such as neuronal firing and excitatory and inhibitory synaptic transmission. As GABAB receptors may be the major target of GHB action, the chronic effects of oral GHB should be dampened by GABAB receptor antagonists, or should be absent in animals where the GABAB receptor has been genetically ablated. Presently, changes in the CNS caused by GHB abuse are poorly understood. We propose a number of investigations relying on behavioral and electrophysiological examination of orally GHB-treated mice. Each of the three specific aims addresses critical features of the mechanism of action of GHB. The aims are 1) to determine the in vivo neuronal correlates of chronic, oral GHB-administration and withdrawal in wild-type mice and in GABAB receptor knockout mice; 2) to establish the cellular and neuronal network changes in the cerebral cortex in the mice after chronic, oral GHB- administration; and 3) to ascertain whether GABAB-receptor antagonists and GHB-receptor antagonist NCS-382 offer protection against the GHB-induced changes in behavior and cellular properties. To accomplish these goals, oral treatment with GHB will be carried out in mice subjected to behavioral and electrophysiological tests. Furthermore, high resolution electrophysiological recordings will be obtained from neurons identified with IR-DIC methods and anatomical reconstruction of the recorded cells. Selective GABAB receptor antagonists will be used, while the newly generated GABAB receptor knockout animals will serve as an advanced tool to test the involvement of GABAB receptors in these processes. The study is expected to yield novel and specific insights into the GHB-induced changes in the mammalian brain. By developing and characterizing a mouse model of GHB abuse, our study will open the possibility of further using genetically altered mice for studying the effects of GHB on the brain or other organs. Understanding the specific alterations that accompany GHB abuse will lead to a better grasp of the clinical problems associated with GHB ingestion, including acute intoxication, long-term abuse, and the GHB withdrawal syndrome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NEUROPHARMACOLOGY OF GHB DISCRIMINATION Principal Investigator & Institution: Koek, Wouter; Psychiatry; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2006 Summary: (provided by applicant): Recreational use of gamma-hydroxybutyrate (GHB) is increasing dramatically. The pharmacological mechanisms by which GHB produces its abuse-related effects are poorly understood. GHB abuse is likely related to its subjective effects, and subjective effects of drugs in humans can often be predicted from drug discrimination experiments in animals. The discriminative stimulus effects of GHB are likely to be multidimensional and to involve several different receptor mechanisms. Some of these mechanisms may be unique to GHB (i.e., those involving specific GHB receptors), whereas others may be in common with other compounds (i.e., those involving GABAA and GABAB receptors). The studies proposed here will examine the involvement of these mechanisms in the discriminative stimulus effects of GHB under various conditions. Studies under Specific Aim I examine the ability of positive GABAA modulators and agonists at GABAA, GABAB and GHB receptors to substitute for GHB, and the ability of negative GABAA modulators and antagonists at GABAA, GABAB and GHB receptors to attenuate the discriminative stimulus effects of GHB. These substitution and antagonism studies are conducted under conditions involving different training doses of GHB, because the training dose often affects the pharmacological selectivity of the discrimination. Not only the training dose, but also the alterative training condition can affect the pharmacological selectivity, as shown by drug-drug discrimination studies. Studies under Specific Aim II attempt to increase the pharmacological selectivity of the discriminative stimulus effects of GHB by training to discriminate GHB not only from saline, but also from other drugs that share receptor mechanisms with GHB. It is hypothesized that 1) GABAA, GABAB, and GHB receptors each are involved in the discriminative stimulus of GHB, 2) when a low training dose is used the role of GABAA receptors is more prominent, and when a high training dose is used the discrimination will primarily involve GABAB and GHB receptors, and 3) when a high dose of GHB can be discriminated from a GABAB agonist, its discriminative stimulus effects will involve only GHB receptors. By identifying the role of specific receptors in abuse-related effects of GHB, future studies may be better able to develop specific, pharmacologically targeted therapies for GHB abuse. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: RAPID SCREENING METHOD: GAMMA-HYDROXYBUTYRATE DETECTION Principal Investigator & Institution: Mash, Deborah C.; Professor; Neurology; University of Miami-Medical Box 248293 Coral Gables, Fl 33124 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-AUG-2004 Summary: (provided by applicant) This R21 application request support for the development of a rapid method for: gamma-hydroxybutyrate (GHB) detection and measurement in biological fluids. An increasing number of reports indicate that the abuse of GHB is widespread. GHB is regularly encountered in cases of intoxicated drivers and fatal GHB overdoses are reported throughout the country. In Dade County, Florida, a number of fatal intoxications have been documented, some of them due to GHB alone. There are also reports suggesting that GHB is often used to facilitate sexual assault. Particularly in suspected poisoning cases, the need for a rapid method to detect and quantify GHB is obvious, since the symptomatology may be similar to, but the
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management and treatment different from, that of other kinds of intoxications. The analytical methods currently available are mainly based on gas chromatography with flame ionization (GC-FID) or mass spectrometric (GC-MS) techniques that involve laborious extraction steps for sample preparation. These methods are very timeconsuming and inexpedient for use in emergency settings. We propose to develop an enzymatic assay based on the conversion of GHB to succinic semialdehyde as a rapid and specific method for the detection and measurement of GHB in biological fluids. This reaction is catalysed by a group of highly selective GHB dehydrogenase enzymes that utilize either NADP+ or NAD+ as cofactors. The NADPH or NADR produced in stoichiometric quantity by the reaction can be measured spectrophotometrically. Our approach is based upon the same principles as the classic alcohol dehydrogenase method for analysis of ethanol with substitution of highly selective GHB dehydrogenase. The GHB dehydrogenase of Syrian hamster liver, which has been purified and well characterized, will be used to evaluate the accuracy and reliability of the rapid spectrophotometric method of analysis. The rapid and sensitive analytical approach based on 4-hydroxybutyrate catabolism and spectrophotometric detection of the reaction product will be evaluated by comparing the results with a highly specific GC-MS method, currently in use at the toxicology unit of the Miami-Dade County Medical Examiner Office under the direction of Dr. W. Lee Ream. A novel approach will be to extend the methods developed in hamster liver for use with GHB dehydrogenase of Clostridium kluyveri. In this approach, a plasmid vector containing genes that express stable levels of 4-hydroxybutyrate dehydrogenase is grown and expressed in Escherichia coli. The enzyme will be isolated from the culture medium and employed in a reagent system adaptable to automated chemistry analyzers of the types used in medical and drug screening laboratories. In addition, we plan to extend the enzymatic method to develop a rapid spot test based on the same principle. Proof-of-concept and inter-assay validity will be evaluated by comparing the results of both these methods with GC-MS. Both of these methods will be tested on GHB-spiked controls and residual blood and urine specimens obtained from the Miami-Dade County Medical Examiner Department and the Emergency Department of Jackson Memorial Hospital. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RAT MODELS TO SCREEN COMPOUNDS INDUCING SLOW-WAVE SLEEP Principal Investigator & Institution: Bergmann, Bernard M.; Slowave 20 N Wacker Dr, Ste 2200 Chicago, Il 60606 Timing: Fiscal Year 2003; Project Start 01-SEP-2000; Project End 30-JUN-2004 Summary: (provided by applicant): A main goal of SloWave, Inc. is to develop a novel class of sleep-enhancing compounds that, unlike all currently available hypnotics, stimulate slow-wave sleep (SWS), the deepest and most restorative stage of sleep. SloWave plans to develop structural analogs of a natural neuromodulator, gammahydroxybutyrate (GHB), which is a potent stimulant of SWS, and has a specific newly identified receptor system in the brain. The objective of this Phase II proposal is to synthesize and screen compounds with the most potent effects on SWS. The specific aims are: 1. To test about 50 GHB agonists, identified by binding assays to have affinity for the GHB receptor, for their ability to induce changes in locomotor activity and body temperature, and to later test about 10 of the lead compounds for their effects on EEG sleep-wake states. 2. To test important hypotheses concerning the mechanisms of action of GHB by examining the effects of various GABAergic or dopaminergic antagonists on GHB-induced alterations in behavioral or physiological state. 3. To determine the effect
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of chronic treatment with GHB on sleep, and to determine if withdrawal from chronic drug exposure leads to sleep disturbances. The completion of these studies will result in: 1. The identification of 2-3 novel compounds that will subsequently be tested for toxicity prior to human Phase I studies. 2. Increased understanding of the mechanisms of action of GHB on sleep information, which is critical for the design of clinical studies. 3. The definition of the effects of chronic GHB treatment on sleep information, which is important for later pre-clinical studies on the chronic effects of our compounds. The development of GHB related compounds will represent a major breakthrough in the treatment of conditions which involve decreased or abnormal slow-wave sleep, such as aging depression, fibromyalgia and narcolepsy, which together affects many millions of individuals. PROPOSED COMMERCIAL APPLICATION: SloWave will develop a novel class of sleep-enhancing compounds acting via the GHB system which, unlike currently available hypnotics, stimulate slow-wave sleep, the deepest and most restorative stage of sleep, and have a pharmacokinetic profile consistent with the maintenance of sleep and a heightened level of alertness upon awakening. These new compounds will represent a major breakthrough in the treatment of conditions and illnesses which involve disturbed sleep. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SLEEP REGULATION
AND
CIRCADIAN
RHYTHMICITY
IN
GLUCOSE
Principal Investigator & Institution: Van Cauter, Eve; Professor; Medicine; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2002; Project Start 01-JUL-1989; Project End 30-APR-2005 Summary: (Adapted from applicant's abstract): The overall goal of this application is to determine whether decreased resiliency of the HPA axis, (as reflected by increased evening cortisol levels) and/or sleep disturbances (and the associated decreased amounts of slow-wave sleep (SWS) and growth hormone (GH) secretion) adversely affect components of glucose tolerance. Studies to be performed in healthy young subjects will involve the manipulation of stress responses and/or one of its major neuroendocrine correlates (cortisol levels), as well as of sleep and/or one of its major neuroendocrine correlates (GH secretion). These manipulations will include: activation of the HPA axis by exposure to physical exercise or brief psychological stressors, entrainment of insulin secretion and insulin sensitivity to exogenously controlled oscillations of cortisol levels, acute partial sleep deprivation, chronic sleep curtailment and sleep extension, suppression and restoration of nocturnal GH secretion. Studies in middle-aged non-obese adults, who have shallow sleep, decreased GH secretion but normal cortisol profiles will test the hypothesis that the restoration of deep sleep by pharmacological treatment will increase nocturnal GH secretion and improve components of glucose tolerance on the next day. Studies in young obese subjects, who have normal sleep, decreased GH secretion and elevated evening cortisol levels will test the hypotheses that the abnormal diurnal variation in glucose tolerance associated with obesity is partially caused by the elevation of evening cortisol levels and that the restoration of sleep onset GH secretion by bedtime injection of exogenous GH will have beneficial effects on glucose regulation. In all studies, the primary output measures will be components of glucose tolerance, including beta-cell responsivity, insulin sensitivity, glucose effectiveness and insulin clearance. Taken together, the results of these studies should demonstrate the interactive roles of sleep quality and resilience to stress in the maintenance of normal glucose tolerance, and determine whether approaches to correct
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Gamma Hydroxybutyrate
age-related reductions in sleep quality could prevent or delay the development of impaired glucose tolerance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TRENDS IN CLUB DRUG USE Principal Investigator & Institution: Krebs, Christopher P.; Research Social Scientist; Research Triangle Institute Box 12194, 3040 Cornwallis Rd Research Triangle Park, Nc 277092194 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 30-MAY-2004 Summary: (provided by the applicant): Recent evidence suggests that club drugs, such as lysergic acid diethylamide (LSD), methylene-dioxy-methamphetamine (MDMA or Ecstasy), gamma-hydroxybutyrate (GHB), Ketamine, Rohypnol, methamphetamine, and psilocybin, are gaining in popularity, users are getting younger, and serious consequences can result from using these substances. These factors have caused alarm among many in the public health, law enforcement, and policy-making communities. Much of this concern stems from the fact that we know very little about the factors that affect club drug trends, the people who use these substances, and the exact method in which they are used. The proposed study involves interviewing a sample of 250 juvenile offenders in Lane County (Eugene), Oregon, that is racially/ethnically diverse, includes both genders, and reports high rates of club drug use. Additionally, a sample 30 juveniles who have extensive experience with club drugs and the rave scene will be administered a detailed, qualitative interview. The proposed investigation will (1) determine whether users of various club drugs are "different" from non-club drug users or users of other drugs in terms of demographic characteristics, life experiences, etc.; (2) identify how, where, and from whom youth learn about and obtain various club drugs and how much they spend on them; (3) ascertain where, when, how, and in what social contexts youth use club drugs and what substances they mix with them; (4) document youth attitudes and beliefs about various club drugs and reasons why they use them; and (5) determine whether youth have experienced or witnessed any consequences of using various club drugs. Simple descriptive analyses, as well as multivariate binomial logistic, multinomial logistic, mixed-effects ordinal regression, latent class, and attributable risk models, will be employed to achieve the specific aims outlined above. An effort will be made to test several etiological models of club drug use, identify risk and protective factors, and understand the subculture that embraces these substances. This information will help inform subsequent research on club drugs and substancespecific education/prevention and interdiction initiatives. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: YOUTH, TECHNOLOGY, AND THE PROLIFERATION OF DRUG USE Principal Investigator & Institution: Murguia, Edward E.; Associate Professor; Sociology; Texas A&M University System College Station, Tx 778433578 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-AUG-2003 Summary: (provided by the applicant): Several drugs, popularly used by adolescents at dance parties, raves, and clubs, have been shown to be a serious health concern to medical researchers. MDMA (ecstasy), Lysergic Acid Diethylamide (LSD), Rohypnol, Methamphetamine, Ketamine, and Gammahydroxybutyrate (GBH) are substances generally labeled "club drugs." Such drugs, while not necessarily new, have gained recent popularity though use at raves. The impact of these drugs on the health of youth
Studies
21
has been researched in recent decades. While results are mixed, studies do suggest that ecstasy in particular may be associated with convulsions, cardiac and pulmonary problems, hypothermia, and in rare instances, death. However, ecstasy and other club drugs are most dangerous when used in combination. According to a recent SAMHSA Dawn Report, most medical emergency incidents involving club drugs also involved the use of alcohol, marijuana, cocaine, and other club drugs. Additional work also suggests that the use of polydrugs is common in the rave/club scene. This study proposes to explore the relationship between the Internet and the transmission of information among youth about "club drugs." The Internet has figured prominently in the "rave scene" since the early years of the movement. The Internet has been a primary site of communication about rave parties, DJs, and artists. Moreover, it provides space for youth to connect with others involved in the rave scene through chat rooms and email subscription lists. While raves, house and bush parties change locale often, the setting of web-based interaction remains static and constant. The role of Internet interaction in the use of club drugs has been unexplored. The current research proposes an Internet-based qualitative study of youth involved in Internet chat rooms and discussion boards. The goal of the research is to solicit new and pertinent information related to the context and setting of club drug use (e.g., when, where, and with whom are drugs primarily used; under what circumstances are some drugs chosen over others; etc.). Moreover, it will explore the role of the Internet in transferring and mediating information regarding drug use across settings (e.g., is the Internet a source of new information about drugs among users, how is Internet use related to the local club scene; do drug use trends disseminate through a "virtual community" or through local, geographically tied networks, how can the Internet be used a prevention and education tool among "club drug" users; etc.). For these reasons, the methodology for this project will involve the extension and adaptation of traditional ethnographic methods to the practice of cyberethnography. The project team will combine, as well as adapt field methods for what will at first be a largely unseen group of subjects. We will engage in a two-pronged approach to capture both the online and off-line (so-called 'real life') interactions and networks of the subjects. Primarily, field notes will be generated by monitoring online sites and participant observation in site-communications and other Internet-based communications with members of these communities (e.g. email and America Online Instant Messaging). In addition, we will construct an online survey administered to interested members. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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.3 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. 3
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.
22
Gamma Hydroxybutyrate
To generate your own bibliography of studies dealing with gamma hydroxybutyrate, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “gamma hydroxybutyrate” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for gamma hydroxybutyrate (hyperlinks lead to article summaries): •
"Grievous bodily harm:" gamma hydroxybutyrate abuse leading to a WernickeKorsakoff syndrome. Author(s): Friedman J, Westlake R, Furman M. Source: Neurology. 1996 February; 46(2): 469-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8614515
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"There is no substantive due process right to conduct human-subject research": the saga of the Minnesota Gamma Hydroxybutyrate Study. Author(s): Hammerschmidt DE. Source: Irb. 1997 May-August; 19(3-4): 13-5. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11656944
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Acute toxicity from home-brewed gamma hydroxybutyrate. Author(s): Hodges B, Everett J. Source: The Journal of the American Board of Family Practice / American Board of Family Practice. 1998 March-April; 11(2): 154-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9542708
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Another case of gamma hydroxybutyrate (GHB) overdose. Author(s): James C. Source: Journal of Emergency Nursing: Jen : Official Publication of the Emergency Department Nurses Association. 1996 April; 22(2): 97. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8716296
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Cardiovascular reactions to gamma hydroxybutyrate in man. Author(s): Virtue RW, Lund LO, Beckwitt HJ, Vogel JH. Source: Can Anaesth Soc J. 1966 March; 13(2): 119-23. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5959489
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Gamma hydroxybutyrate (GHB) and gamma butyrolactone (GBL) withdrawal: five case studies. Author(s): McDaniel CH, Miotto KA. Source: J Psychoactive Drugs. 2001 April-June; 33(2): 143-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11476261
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•
Gamma hydroxybutyrate (GHB): report of a mass intoxication and review of the literature. Author(s): Eckstein M, Henderson SO, DelaCruz P, Newton E. Source: Prehosp Emerg Care. 1999 October-December; 3(4): 357-61. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10534040
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Gamma hydroxybutyrate is not a GABA agonist. Author(s): Feigenbaum JJ, Howard SG. Source: Progress in Neurobiology. 1996 September; 50(1): 1-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8931105
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Gamma hydroxybutyrate overdose: two cases illustrate the unique aspects of this dangerous recreational drug. Author(s): Ross TM. Source: Journal of Emergency Nursing: Jen : Official Publication of the Emergency Department Nurses Association. 1995 October; 21(5): 374-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7500561
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Gamma hydroxybutyrate poisoning. Author(s): Libetta C. Source: Journal of Accident & Emergency Medicine. 1997 November; 14(6): 411. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9413785
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Gamma hydroxybutyrate withdrawal in an orthopedic trauma patient. Author(s): Slagel B, Kingstone E, Bhalerao S. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2003 March; 48(2): 131-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12655920
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Gamma hydroxybutyrate. Author(s): Snead OC 3rd. Source: Life Sciences. 1977 June 15; 20(12): 1935-43. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=329034
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Gamma hydroxybutyrate--a coma inducing recreational drug. Author(s): Ryan JM, Stell I. Source: Journal of Accident & Emergency Medicine. 1997 July; 14(4): 259-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9248920
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Gamma Hydroxybutyrate
•
Long-term therapy using GHB (sodium gamma hydroxybutyrate) for treatmentresistant chronic alcoholics. Author(s): Maremmani I, Lamanna F, Tagliamonte A. Source: J Psychoactive Drugs. 2001 April-June; 33(2): 135-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11476260
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Pediatric gamma hydroxybutyrate intoxication. Author(s): Suner S, Szlatenyi CS, Wang RY. Source: Academic Emergency Medicine : Official Journal of the Society for Academic Emergency Medicine. 1997 November; 4(11): 1041-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9383489
•
Sodium gamma hydroxybutyrate: laboratory and clinical studies. Author(s): Lund LO, Humphries JH, Virtue RW. Source: Can Anaesth Soc J. 1965 July; 12(4): 379-85. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5891226
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The effect of gamma hydroxybutyrate on serum osmolality. Author(s): Ingels M, Kelner MJ, Clark RF. Source: Journal of Toxicology. Clinical Toxicology. 2001; 39(4): 417-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11527239
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Unsupported "Efficacy" claims of gamma hydroxybutyrate (GHB). Author(s): Zvosec DL, Smith SW. Source: Academic Emergency Medicine : Official Journal of the Society for Academic Emergency Medicine. 2003 January; 10(1): 95-6; Author Reply 96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12511324
25
CHAPTER
2.
NUTRITION AND HYDROXYBUTYRATE
GAMMA
Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and gamma hydroxybutyrate.
Finding Nutrition Studies on Gamma Hydroxybutyrate 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.4 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 “gamma hydroxybutyrate” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.
4 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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Gamma Hydroxybutyrate
The following information is typical of that found when using the “Full IBIDS Database” to search for “gamma hydroxybutyrate” (or a synonym): •
Acute poisoning from gamma hydroxybutyrate (GHB). Author(s): Department of Emergency Medicine, Truman Medical Center, University of Missouri-Kansas City School of Medicine, USA. Source: Steele, M T Watson, W A Mo-Med. 1995 July; 92(7): 354-7 0026-6620
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
•
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/
•
WebMDHealth: http://my.webmd.com/nutrition
Nutrition
•
WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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CHAPTER 3. ALTERNATIVE MEDICINE AND GAMMA HYDROXYBUTYRATE Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to gamma hydroxybutyrate. At the conclusion of this chapter, we will provide additional sources.
National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to gamma hydroxybutyrate and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “gamma hydroxybutyrate” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to gamma hydroxybutyrate: •
A simple, cheap, effective and safe procedure for general anesthesia. Author(s): Lelkens JP. Source: Acta Anaesthesiol Belg. 1976; 27(2): 25-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1024453
•
Acute poisoning from gamma hydroxybutyrate (GHB). Author(s): Steele MT, Watson WA. Source: Mo Med. 1995 July; 92(7): 354-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7651315
•
Adverse events, including death, associated with the use of 1,4-butanediol. Author(s): Zvosec DL, Smith SW, McCutcheon JR, Spillane J, Hall BJ, Peacock EA.
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Gamma Hydroxybutyrate
Source: The New England Journal of Medicine. 2001 January 11; 344(2): 87-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11150358 •
Alstroemeria L. (Peruvian lily). Author(s): McGovern TW. Source: American Journal of Contact Dermatitis : Official Journal of the American Contact Dermatitis Society. 1999 September; 10(3): 172-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10444112
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Botanical briefs: Peruvian lily--Alstroemeria (L.) spp. Author(s): McGovern TW, Barkley TM. Source: Cutis; Cutaneous Medicine for the Practitioner. 1999 March; 63(3): 137-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10190060
•
Continuum of sedation, activation and hypnosis or hallucinosis: a comparison of low dose effects of pentobarbital, diazepam or gamma-hydroxybutyrate in the cat. Author(s): Winters WD, Kott KS. Source: Neuropharmacology. 1979 November; 18(11): 877-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=575917
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Dose-dependent pharmacokinetics and hypnotic effects of sodium gammahydroxybutyrate in the rat. Author(s): Lettieri JT, Fung HL. Source: The Journal of Pharmacology and Experimental Therapeutics. 1979 January; 208(1): 7-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=759616
•
Drug dependence studies and regulations: an overview of the past and present. Author(s): Harris LS. Source: Nihon Shinkei Seishin Yakurigaku Zasshi. 2001 November; 21(5): 171-4. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11797422
•
Drugs, drink'n and smok'n. Part II. Author(s): Moreno M. Source: Surviv News (Atlanta Ga). 2001 September; : 10-1, 20. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11682788
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EEG-synchronizing effect of gamma-hydroxybutyrate and 1-hydroxy-3-aminopyrrolidone-2 (HA-966) in relation to dopaminergic brain function. Author(s): Dzoljic MR, Bonta IL, Godschalk M, Lagendijk A, Stefanko S.
Alternative Medicine 31
Source: Neuropharmacology. 1975 August; 14(8): 591-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=170556 •
Effects of drugs on the electrical activity of the brain: anesthetics. Author(s): Winters WD. Source: Annual Review of Pharmacology and Toxicology. 1976; 16: 413-26. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=779620
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Elevated GHB in citrate-buffered blood. Author(s): LeBeau MA, Montgomery MA, Jufer RA, Miller ML. Source: Journal of Analytical Toxicology. 2000 July-August; 24(5): 383-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10926365
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Emerging drugs of abuse in Connecticut. Author(s): Weiner AL. Source: Conn Med. 2000 January; 64(1): 19-23. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10697361
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Gamma-hydroxybutyrate, gamma-butyrolactone, and 1,4-butanediol: a case report and review of the literature. Author(s): Shannon M, Quang LS. Source: Pediatric Emergency Care. 2000 December; 16(6): 435-40. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11138892
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gamma-Hydroxybutyrate: a health-food product producing coma and seizurelike activity. Author(s): Dyer JE. Source: The American Journal of Emergency Medicine. 1991 July; 9(4): 321-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2054002
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Involvement of drugs in sexual assault. Author(s): Slaughter L. Source: J Reprod Med. 2000 May; 45(5): 425-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10845178
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Ligand-specific control of src-suppressed C kinase substrate gene expression. Author(s): Coats SR, Pabon-Pena LM, Covington JW, Vaughan DE. Source: Biochemical and Biophysical Research Communications. 2002 October 11; 297(5): 1112-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12372401
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Methylation of adjacent CpG sites affects Sp1/Sp3 binding and activity in the p21(Cip1) promoter. Author(s): Zhu WG, Srinivasan K, Dai Z, Duan W, Druhan LJ, Ding H, Yee L, VillalonaCalero MA, Plass C, Otterson GA. Source: Molecular and Cellular Biology. 2003 June; 23(12): 4056-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12773551
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Narcolepsy: pathogenesis and nursing care. Author(s): Bergstrom DL, Keller C. Source: The Journal of Neuroscience Nursing : Journal of the American Association of Neuroscience Nurses. 1992 June; 24(3): 153-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1645038
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Near-fatal gamma-butyrolactone intoxication--first report in the UK. Author(s): Dupont P, Thornton J. Source: Human & Experimental Toxicology. 2001 January; 20(1): 19-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11339620
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Procedure of bidirectional selective outbreeding for production of two rat lines differing in sensitivity to the sedative/hypnotic effect of gamma-hydroxybutyric acid. Author(s): Lobina C, Colombo G, Brunetti G, Diaz G, Melis S, Pani M, Serra S, Vacca G, Gessa GL, Carai MA. Source: Brain Research. Brain Research Protocols. 2001 August; 8(1): 74-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11522530
•
The many faces of ecstasy. Author(s): Doyon S. Source: Current Opinion in Pediatrics. 2001 April; 13(2): 170-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11317061
•
Verve and Jolt: deadly new Internet drugs. Author(s): Winickoff JP, Houck CS, Rothman EL, Bauchner H. Source: Pediatrics. 2000 October; 106(4): 829-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11015528
Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •
Alternative Medicine Foundation, Inc.: http://www.herbmed.org/
•
AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats
Alternative Medicine 33
•
Chinese Medicine: http://www.newcenturynutrition.com/
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drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html
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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm
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Google: http://directory.google.com/Top/Health/Alternative/
•
Healthnotes: http://www.healthnotes.com/
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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine
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Open Directory Project: http://dmoz.org/Health/Alternative/
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HealthGate: http://www.tnp.com/
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WebMDHealth: http://my.webmd.com/drugs_and_herbs
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
•
Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/
The following is a specific Web list relating to gamma hydroxybutyrate; 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: •
Herbs and Supplements HMB (Hydroxymethyl Butyrate) Source: Prima Communications, Inc.www.personalhealthzone.com
General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.
35
CHAPTER
4.
DISSERTATIONS ON HYDROXYBUTYRATE
GAMMA
Overview In this chapter, we will give you a bibliography on recent dissertations relating to gamma hydroxybutyrate. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “gamma hydroxybutyrate” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on gamma hydroxybutyrate, we have not necessarily excluded non-medical dissertations in this bibliography.
Dissertations on Gamma Hydroxybutyrate ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to gamma hydroxybutyrate. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •
The pharmacology of gamma valerolactone (GVL) as compared to gamma hydroxybutyrate (GHB), gamma butyrolactone (GBL), 1,4 butanediol (1,4 BD), ethanol (EtOH) and baclofen (BAC) in the rat by Marinetti, Laureen J., PhD from Wayne State University, 2003, 219 pages http://wwwlib.umi.com/dissertations/fullcit/3116516
Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.
37
CHAPTER 5. PATENTS ON GAMMA HYDROXYBUTYRATE 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.5 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 “gamma hydroxybutyrate” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on gamma hydroxybutyrate, we have not necessarily excluded non-medical patents in this bibliography.
Patent Applications on Gamma Hydroxybutyrate As of December 2000, U.S. patent applications are open to public viewing.6 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 gamma hydroxybutyrate:
5Adapted
from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm. 6 This has been a common practice outside the United States prior to December 2000.
38
•
Gamma Hydroxybutyrate
Detection of abused substances and their metabolites using nucleic acid sensor molecules Inventor(s): Seiwert, Scott; (Pacifica, CA) Correspondence: Mcdonnell Boehnen Hulbert & Berghoff; 300 South Wacker Drive; Suite 3200; Chicago; IL; 60606; US Patent Application Number: 20030224435 Date filed: May 16, 2003 Abstract: Nucleic acid sensor molecules (allozymes, allosteric ribozymes, allosteric DNAzymes), aptamers and methods are provided for the detection and quantitation of small molecules, including drugs, drug analogs, and drug metabolites, for example recreational drugs, mood-altering drugs, and performance enhancing drugs such as 4MTA (4-methylthioamphetamine), Alpha-ethyltryptamine, Amphetamine, Amyl nitrite, Benzocaine, Cocaine, Dimethyltryptamine, Ecstasy (MDA, MDMA, MDEA), Ephedrine, Erythropoietine (Epogen), Fentanyl, Gamma Hydroxybutyrate (GHB), GBL (Gamma butyrolactone), GHB (Gamma Hydroxybutyrate), Hashish, Heroin, Isobutyl nitrite, Ketamine, Lidocaine, LSD (Lysergic acid diethylamide), Mannitol, Marijuana (THC), Mescaline, Methadone, Methamphetamine, Methaqualone, Methcathinone, Methylphenidate (ritalin), Morphine, Nexus (2CB), Nicotine, Opium, Oxycodone, OxyContin, PCP (phencyclidine), Peyote, Phenobarbital, Procaine, Psilocybin, Psilocybin/psilocin, Pseudoephedrine, Rohypnol, Scopolamine, Steroids, Strychnine, and Talwin. Also provided are kits for detection. The nucleic acid sensor molecules, methods and kits provided herein can be used in diagnositic applications for detecting drugs, analogs, and metabolites thereof. Excerpt(s): This patent application claims the benefit of U.S. Ser. No. 60/381,006, filed May 16, 2002. This application is hereby incorporated by reference herein in its entirety including the drawings. This invention relates generally to the field of drug and drug metabolite detection in biological samples. More specifically, it provides a system for detecting or confirming the presence of a particular drug analyte in a sample that potentially contains interfering substances. This invention specifically relates to novel molecular sensors that utilize enzymatic nucleic acid constructs whose activity can be modulated by the presence or absence of signaling agents that include compounds and substances of abuse, such as recreational drugs, mood altering drugs, performance enhancing drugs, analgesics, and metabolites thereof. The present invention further relates to the use of the enzymatic nucleic acid constructs as molecular sensors capable of modulating the activity, function, or physical properties of other molecules useful in detecting compounds and substances of abuse and metabolites thereof. The invention also relates to the use of the enzymatic nucleic acid constructs as diagnostic reagents, useful in identifying such signaling agents in a variety of applications, for example, in screening biological samples or fluids for compounds and substances of abuse and metabolites thereof. The ability to perform rapid screening tests in diagnostic analysis of biological samples has been considerably facilitated by the evolving art of immunoassay. Antibodies can be raised that have exquisite specificity and sensitivity for small molecules of diagnostic interest, such as drugs and drug metabolites. In combination with other reagents that have a separating or labeling function, specific antibodies can be used as part of a rapid screening test for the presence of the small molecule in a clinical sample. Similarly, nucleic acid technology can be applied to develop polynucleotide based detection systems comprising nucleic acid molecules with high affinity for a particular small molecule target. Furthermore, the functionality of enzymatic nucleic acid molecules can be coupled with these recognition properties in
Patents 39
the design of nucleic acid sensor molecules having both recognition and signal generating capability. 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 gamma hydroxybutyrate, 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 “gamma hydroxybutyrate” (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 gamma hydroxybutyrate. You can also use this procedure to view pending patent applications concerning gamma hydroxybutyrate. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.
41
CHAPTER 6. PERIODICALS AND NEWS ON GAMMA HYDROXYBUTYRATE Overview In this chapter, we suggest a number of news sources and present various periodicals that cover gamma hydroxybutyrate.
News Services and Press Releases One of the simplest ways of tracking press releases on gamma hydroxybutyrate 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 “gamma hydroxybutyrate” (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 gamma hydroxybutyrate. 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 “gamma hydroxybutyrate” (or synonyms).
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Gamma Hydroxybutyrate
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 “gamma hydroxybutyrate” (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 “gamma hydroxybutyrate” (or synonyms). If you know the name of a company that is relevant to gamma hydroxybutyrate, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “gamma hydroxybutyrate” (or synonyms).
Periodicals and News
43
Academic Periodicals covering Gamma Hydroxybutyrate Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to gamma hydroxybutyrate. In addition to these sources, you can search for articles covering gamma hydroxybutyrate 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.”
45
APPENDICES
47
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 Institute7: •
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/
7
These publications are typically written by one or more of the various NIH Institutes.
48
Gamma Hydroxybutyrate
•
National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm
•
National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
•
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
•
National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
•
National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
•
National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
•
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
•
National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
•
National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
•
National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
•
National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm
•
National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
•
National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
•
Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
•
National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
•
National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
•
Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
•
Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm
Physician Resources
49
NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.8 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:9 •
Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html
•
HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
•
NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html
•
Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/
•
Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html
•
Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
•
Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
•
Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
•
Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html
•
Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
•
MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html
8
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). 9 See http://www.nlm.nih.gov/databases/databases.html.
50
Gamma Hydroxybutyrate
•
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 Gateway10 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.11 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “gamma hydroxybutyrate” (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 1238 5 576 1 7 1827
HSTAT12 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.13 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.14 Simply search by “gamma hydroxybutyrate” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
10
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
11
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). 12 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 13 14
The HSTAT URL is http://hstat.nlm.nih.gov/.
Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.
Physician Resources
51
Coffee Break: Tutorials for Biologists15 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.16 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.17 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/.
15 Adapted 16
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. 17 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 gamma hydroxybutyrate 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 gamma hydroxybutyrate. 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 gamma hydroxybutyrate. 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 “gamma hydroxybutyrate”:
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Gamma Hydroxybutyrate
Anabolic Steroids http://www.nlm.nih.gov/medlineplus/anabolicsteroids.html Club Drugs http://www.nlm.nih.gov/medlineplus/clubdrugs.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 gamma hydroxybutyrate. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats
•
Family Village: http://www.familyvillage.wisc.edu/specific.htm
•
Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
•
Med Help International: http://www.medhelp.org/HealthTopics/A.html
•
Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
•
Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
•
WebMDHealth: http://my.webmd.com/health_topics
Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to gamma hydroxybutyrate. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with gamma hydroxybutyrate.
Patient Resources
55
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 gamma hydroxybutyrate. 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 “gamma hydroxybutyrate” (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 “gamma hydroxybutyrate”. 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 “gamma hydroxybutyrate” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “gamma hydroxybutyrate” (or a synonym) into the search box, and click “Submit Query.”
57
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.18
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
18
Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.
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Gamma Hydroxybutyrate
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)19: •
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
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California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/
•
California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/
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California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/
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California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html
•
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/
19
Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
Finding Medical Libraries
59
•
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
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Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
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Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
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Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
•
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
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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
61
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Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm
•
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
63
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
65
GAMMA HYDROXYBUTYRATE DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Acetone: A colorless liquid used as a solvent and an antiseptic. It is one of the ketone bodies produced during ketoacidosis. [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] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of cyclic AMP and pyrophosphate from ATP. EC 4.6.1.1. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [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] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] 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
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substances. [EU] Alcohol Dehydrogenase: An enzyme that catalyzes reversibly the final step of alcoholic fermentation by reducing an aldehyde to an alcohol. In the case of ethanol, acetaldehyde is reduced to ethanol in the presence of NADH and hydrogen. The enzyme is a zinc protein which acts on primary and secondary alcohols or hemiacetals. EC 1.1.1.1. [NIH] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] 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] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amphetamine: A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is dextroamphetamine. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH]
Dictionary 67
Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] 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] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]
Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticonvulsants: Drugs used to prevent seizures or reduce their severity. [NIH] Antidote: A remedy for counteracting a poison. [EU] Antiepileptic: An agent that combats epilepsy. [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] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Aseptic: Free from infection or septic material; sterile. [EU] Aspartate: A synthetic amino acid. [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] Baclofen: A GABA derivative that is a specific agonist at GABA-B receptors. It is used in the treatment of spasticity, especially that due to spinal cord damage. Its therapeutic effects
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result from actions at spinal and supraspinal sites, generally the reduction of excitatory transmission. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [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] Barbiturates: A class of chemicals derived from barbituric acid or thiobarbituric acid. Many of these are medically important as sedatives and hypnotics (sedatives, barbiturate), as anesthetics, or as anticonvulsants. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Benzene: Toxic, volatile, flammable liquid hydrocarbon biproduct of coal distillation. It is used as an industrial solvent in paints, varnishes, lacquer thinners, gasoline, etc. Benzene causes central nervous system damage acutely and bone marrow damage chronically and is carcinogenic. It was formerly used as parasiticide. [NIH] Benzodiazepines: A two-ring heterocyclic compound consisting of a benzene ring fused to a diazepine ring. Permitted is any degree of hydrogenation, any substituents and any Hisomer. [NIH] 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] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [NIH] Bladder: The organ that stores urine. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber.
Dictionary 69
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] Bronchiseptica: A small, gram-negative, motile bacillus. A normal inhabitant of the respiratory tract in man, dogs, and pigs, but is also associated with canine infectious tracheobronchitis and atrophic rhinitis in pigs. [NIH] Buprenorphine: A derivative of the opioid alkaloid thebaine that is a more potent and longer lasting analgesic than morphine. It appears to act as a partial agonist at mu and kappa opioid receptors and as an antagonist at delta receptors. The lack of delta-agonist activity has been suggested to account for the observation that buprenorphine tolerance may not develop with chronic use. [NIH] Butyric Acid: A four carbon acid, CH3CH2CH2COOH, with an unpleasant odor that occurs in butter and animal fat as the glycerol ester. [NIH] Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium Channels: Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue. [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] Cardiovascular: Having to do with the heart and blood vessels. [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
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excreted compounds. [EU] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Caudate Nucleus: Elongated gray mass of the neostriatum located adjacent to the lateral ventricle of the brain. [NIH] 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 membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Cortex: The thin layer of gray matter on the surface of the cerebral hemisphere that develops from the telencephalon and folds into gyri. It reaches its highest development in man and is responsible for intellectual faculties and higher mental functions. [NIH] 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] Chromosomal: Pertaining to chromosomes. [EU] Chronic: A disease or condition that persists or progresses over a long period of time. [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] Coca: Any of several South American shrubs of the Erythroxylon genus (and family) that yield cocaine; the leaves are chewed with alum for CNS stimulation. [NIH] Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. [NIH] 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
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high content of polar groups which are responsible for its swelling properties. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [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] 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]
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Consciousness: Sense of awareness of self and of the environment. [NIH] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] 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 Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curare: Plant extracts from several species, including Strychnos toxifera, S. castelnaei, S. crevauxii, and Chondodendron tomentosum, that produce paralysis of skeletal muscle and are used adjunctively with general anesthesia. These extracts are toxic and must be used with the administration of artificial respiration. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] Delirium: (DSM III-R) an acute, reversible organic mental disorder characterized by reduced ability to maintain attention to external stimuli and disorganized thinking as manifested by rambling, irrelevant, or incoherent speech; there are also a reduced level of consciousness, sensory misperceptions, disturbance of the sleep-wakefulness cycle and level of psychomotor activity, disorientation to time, place, or person, and memory impairment. Delirium may be caused by a large number of conditions resulting in derangement of cerebral metabolism, including systemic infection, poisoning, drug intoxication or withdrawal, seizures or head trauma, and metabolic disturbances such as hypoxia, hypoglycaemia, fluid, electrolyte, or acid-base imbalances, or hepatic or renal failure. Called also acute confusional state and acute brain syndrome. [EU] Delusions: A false belief regarding the self or persons or objects outside the self that persists despite the facts, and is not considered tenable by one's associates. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dextroamphetamine: The d-form of amphetamine. It is a central nervous system stimulant and a sympathomimetic. It has also been used in the treatment of narcolepsy and of attention deficit disorders and hyperactivity in children. Dextroamphetamine has multiple
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mechanisms of action including blocking uptake of adrenergics and dopamine, stimulating release of monamines, and inhibiting monoamine oxidase. It is also a drug of abuse and a psychotomimetic. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrimination: The act of qualitative and/or quantitative differentiation between two or more stimuli. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [EU] Disposition: A tendency either physical or mental toward certain diseases. [EU] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Diuresis: Increased excretion of urine. [EU] Diurnal: Occurring during the day. [EU] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Drug Combinations: Single preparations containing two or more active agents, for the purpose of their concurrent administration as a fixed dose mixture. It is differentiated from combination drug therapy in which two or more drugs are administered separately for a combined effect. [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] 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]
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Electrode: Component of the pacing system which is at the distal end of the lead. It is the interface with living cardiac tissue across which the stimulus is transmitted. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endorphins: One of the three major groups of endogenous opioid peptides. They are large peptides derived from the pro-opiomelanocortin precursor. The known members of this group are alpha-, beta-, and gamma-endorphin. The term endorphin is also sometimes used to refer to all opioid peptides, but the narrower sense is used here; opioid peptides is used for the broader group. [NIH] Enkephalins: One of the three major families of endogenous opioid peptides. The enkephalins are pentapeptides that are widespread in the central and peripheral nervous systems and in the adrenal medulla. [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] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [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] Ergot: Cataract due to ergot poisoning caused by eating of rye cereals contaminated by a fungus. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [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] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excitability: Property of a cardiac cell whereby, when the cell is depolarized to a critical level (called threshold), the membrane becomes permeable and a regenerative inward current causes an action potential. [NIH]
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Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Exhaustion: The feeling of weariness of mind and body. [NIH] 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] Extrapyramidal: Outside of the pyramidal tracts. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] 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] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Flame Ionization: Pyrolysis of organic compounds at the temperature of a hydrogen-air flame to produce ionic intermediates which can be collected and the resulting ion current measured by gas chromatography. [NIH] Flatus: Gas passed through the rectum. [NIH] Flunitrazepam: Benzodiazepine with pharmacologic actions similar to those of diazepam. The United States Government has banned the importation of this drug. Steps are being taken to reclassify this substance as a Schedule 1 drug with no accepted medical use. [NIH] Focus Groups: A method of data collection and a qualitative research tool in which a small group of individuals are brought together and allowed to interact in a discussion of their opinions about topics, issues, or questions. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Forskolin: Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant Coleus forskohlii. Has antihypertensive, positive ionotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland. [NIH] Gamma-hydroxybutyrate: Anxiolytic. [NIH]
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Gap Junctions: Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of connexins, the family of proteins which form the junctions. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]
Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Genetic 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] 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] Glottis: The vocal apparatus of the larynx, consisting of the true vocal cords (plica vocalis) and the opening between them (rima glottidis). [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 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] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]
Glutamine: A non-essential amino acid present abundantly throught the body and is involved in many metabolic processes. It is synthesized from glutamic acid and ammonia. It is the principal carrier of nitrogen in the body and is an important energy source for many cells. [NIH] Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid
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metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]
Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Hallucinogen: A hallucination-producing drug, a category of drugs producing this effect. The user of a hallucinogenic drug is almost invariably aware that what he is seeing are hallucinations. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Hepatic: Refers to the liver. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]
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] 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] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [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] Hydrogenation: Specific method of reduction in which hydrogen is added to a substance by the direct use of gaseous hydrogen. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypnotic: A drug that acts to induce sleep. [EU]
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Hypoglycaemia: An abnormally diminished concentration of glucose in the blood, which may lead to tremulousness, cold sweat, piloerection, hypothermia, and headache, accompanied by irritability, confusion, hallucinations, bizarre behaviour, and ultimately, convulsions and coma. [EU] Hypotension: Abnormally low blood pressure. [NIH] Hypothermia: Lower than normal body temperature, especially in warm-blooded animals; in man usually accidental or unintentional. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Immune response: The activity of the immune system against foreign substances (antigens). [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] Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] 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] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Incubation period: The period of time likely to elapse between exposure to the agent of the disease and the onset of clinical symptoms. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]
Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU]
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Inoculum: The spores or tissues of a pathogen that serve to initiate disease in a plant. [NIH] Inotropic: Affecting the force or energy of muscular contractions. [EU] Insomnia: Difficulty in going to sleep or getting enough sleep. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Intestinal: Having to do with the intestines. [NIH] Intestines: The section of the alimentary canal from the stomach to the anus. It includes the large intestine and small intestine. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intraocular: Within the eye. [EU] Intraocular pressure: Pressure of the fluid inside the eye; normal IOP varies among individuals. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Involuntary: Reaction occurring without intention or volition. [NIH] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] Ion Exchange: Reversible chemical reaction between a solid, often an ION exchange resin, and a fluid whereby ions may be exchanged from one substance to another. This technique is used in water purification, in research, and in industry. [NIH] 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] 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] Ketamine: A cyclohexanone derivative used for induction of anesthesia. Its mechanism of action is not well understood, but ketamine can block NMDA receptors (receptors, NMethyl-D-Aspartate) and may interact with sigma receptors. [NIH] Ketone Bodies: Chemicals that the body makes when there is not enough insulin in the blood and it must break down fat for its energy. Ketone bodies can poison and even kill body cells. When the body does not have the help of insulin, the ketones build up in the blood and then "spill" over into the urine so that the body can get rid of them. The body can also rid itself of one type of ketone, called acetone, through the lungs. This gives the breath a fruity odor. Ketones that build up in the body for a long time lead to serious illness and coma. [NIH] Kinetic: Pertaining to or producing motion. [EU] Latent: Phoria which occurs at one distance or another and which usually has no
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troublesome effect. [NIH] Lipid: Fat. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Locomotor: Of or pertaining to locomotion; pertaining to or affecting the locomotive apparatus of the body. [EU] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lysergic acid: A compound close in chemical structure to LSD-25 but without hallucinogenic effects; one of the direct chemical predecessors of LSD-25. Sometimes LSD-25 is erroneously called by this name. [NIH] Lysergic Acid Diethylamide: Semisynthetic derivative of ergot (Claviceps purpurea). It has complex effects on serotonergic systems including antagonism at some peripheral serotonin receptors, both agonist and antagonist actions at central nervous system serotonin receptors, and possibly effects on serotonin turnover. It is a potent hallucinogen, but the mechanisms of that effect are not well understood. [NIH] Manic: Affected with mania. [EU] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] 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] Mesolimbic: Inner brain region governing emotion and drives. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Methamphetamine: A central nervous system stimulant and sympathomimetic with actions and uses similar to dextroamphetamine. The smokable form is a drug of abuse and is referred to as crank, crystal, crystal meth, ice, and speed. [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]
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Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microglia: The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling. [NIH] 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] Monoamine: Enzyme that breaks down dopamine in the astrocytes and microglia. [NIH] Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. [NIH] Motor Activity: The physical activity of an organism as a behavioral phenomenon. [NIH] Motor nerve: An efferent nerve conveying an impulse that excites muscular contraction. [NIH]
Muscle relaxant: An agent that specifically aids in reducing muscle tension, as those acting at the polysynaptic neurons of motor nerves (e.g. meprobamate) or at the myoneural junction (curare and related compounds). [EU] Muscle tension: A force in a material tending to produce extension; the state of being stretched. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Naltrexone: Derivative of noroxymorphone that is the N-cyclopropylmethyl congener of naloxone. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. The FDA has approved naltrexone for the treatment of alcohol dependence. [NIH] Narcolepsy: A condition of unknown cause characterized by a periodic uncontrollable tendency to fall asleep. [NIH] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [EU] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH]
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Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neuroblastoma: Cancer that arises in immature nerve cells and affects mostly infants and children. [NIH] Neuroendocrine: Having to do with the interactions between the nervous system and the endocrine system. Describes certain cells that release hormones into the blood in response to stimulation of the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] 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] 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] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleus Accumbens: Collection of pleomorphic cells in the caudal part of the anterior horn of the lateral ventricle, in the region of the olfactory tubercle, lying between the head of the caudate nucleus and the anterior perforated substance. It is part of the so-called ventral striatum, a composite structure considered part of the basal ganglia. [NIH] Nursing Care: Care given to patients by nursing service personnel. [NIH] Opiate: A remedy containing or derived from opium; also any drug that induces sleep. [EU] Opium: The air-dried exudate from the unripe seed capsule of the opium poppy, Papaver somniferum, or its variant, P. album. It contains a number of alkaloids, but only a few morphine, codeine, and papaverine - have clinical significance. Opium has been used as an analgesic, antitussive, antidiarrheal, and antispasmodic. [NIH] Osmolality: The concentration of osmotically active particles in solution expressed in terms of osmoles of solute per kilogram of solvent. The osmolality is directly proportional to the
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colligative properties of solutions; osmotic pressure, boiling point elevation, freezing point depression, and vapour pressure lowering. [EU] Osmoles: The standard unit of osmotic pressure. [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] Overdose: An accidental or deliberate dose of a medication or street drug that is in excess of what is normally used. [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] 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] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Particle: A tiny mass of material. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]
Penicillin: An antibiotic drug used to treat infection. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Pertussis: An acute, highly contagious infection of the respiratory tract, most frequently affecting young children, usually caused by Bordetella pertussis; a similar illness has been associated with infection by B. parapertussis and B. bronchiseptica. It is characterized by a catarrhal stage, beginning after an incubation period of about two weeks, with slight fever, sneezing, running at the nose, and a dry cough. In a week or two the paroxysmal stage
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begins, with the characteristic paroxysmal cough, consisting of a deep inspiration, followed by a series of quick, short coughs, continuing until the air is expelled from the lungs; the close of the paroxysm is marked by a long-drawn, shrill, whooping inspiration, due to spasmodic closure of the glottis. This stage lasts three to four weeks, after which the convalescent stage begins, in which paroxysms grow less frequent and less violent, and finally cease. Called also whooping cough. [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] Phencyclidine: A hallucinogen formerly used as a veterinary anesthetic, and briefly as a general anesthetic for humans. Phencyclidine is similar to ketamine in structure and in many of its effects. Like ketamine, it can produce a dissociative state. It exerts its pharmacological action through inhibition of NMDA receptors (receptors, N-methyl-Daspartate). As a drug of abuse, it is known as PCP and Angel Dust. [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] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]
Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasmid: An autonomously replicating, extra-chromosomal DNA molecule found in many bacteria. Plasmids are widely used as carriers of cloned genes. [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] Pleomorphic: Occurring in various distinct forms. In terms of cells, having variation in the size and shape of cells or their nuclei. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH]
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Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] 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] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] 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] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychoactive: Those drugs which alter sensation, mood, consciousness or other psychological or behavioral functions. [NIH] Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Psychosis: A mental disorder characterized by gross impairment in reality testing as evidenced by delusions, hallucinations, markedly incoherent speech, or disorganized and agitated behaviour without apparent awareness on the part of the patient of the incomprehensibility of his behaviour; the term is also used in a more general sense to refer to mental disorders in which mental functioning is sufficiently impaired as to interfere grossly with the patient's capacity to meet the ordinary demands of life. Historically, the term has been applied to many conditions, e.g. manic-depressive psychosis, that were first
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described in psychotic patients, although many patients with the disorder are not judged psychotic. [EU] Psychotomimetic: Psychosis miming. [NIH] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] 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] Punishment: The application of an unpleasant stimulus or penalty for the purpose of eliminating or correcting undesirable behavior. [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] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Reality Testing: The individual's objective evaluation of the external world and the ability to differentiate adequately between it and the internal world; considered to be a primary ego function. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [NIH] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Relaxant: 1. Lessening or reducing tension. 2. An agent that lessens tension. [EU] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [NIH]
Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Response rate: The percentage of patients whose cancer shrinks or disappears after treatment. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Ritalin: Drug used to treat hyperactive children. [NIH]
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Saline: A solution of salt and water. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] Sedatives, Barbiturate: Those derivatives of barbituric or thiobarbituric acid that are used as hypnotics or sedatives. The structural class of all such derivatives, regardless of use, is barbiturates. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Sensitization: 1. Administration of antigen to induce a primary immune response; priming; immunization. 2. Exposure to allergen that results in the development of hypersensitivity. 3. The coating of erythrocytes with antibody so that they are subject to lysis by complement in the presence of homologous antigen, the first stage of a complement fixation test. [EU] Sensor: A device designed to respond to physical stimuli such as temperature, light, magnetism or movement and transmit resulting impulses for interpretation, recording, movement, or operating control. [NIH] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [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] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]
Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU]
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Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Sleep Deprivation: The state of being deprived of sleep under experimental conditions, due to life events, or from a wide variety of pathophysiologic causes such as medication effect, chronic illness, psychiatric illness, or sleep disorder. [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]
Sneezing: Sudden, forceful, involuntary expulsion of air from the nose and mouth caused by irritation to the mucous membranes of the upper respiratory tract. [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] Sodium-Calcium Exchanger: An electrogenic ion exchange protein that maintains a steady level of calcium by removing an amount of calcium equal to that which enters the cells. It is widely distributed in most excitable membranes, including the brain and heart. [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] Spasmodic: Of the nature of a spasm. [EU] 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] 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] 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] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [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] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or
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tension. Stress may be either physical or psychologic, or both. [NIH] Striatum: A higher brain's domain thus called because of its stripes. [NIH] 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] Subculture: A culture derived from another culture or the aseptic division and transfer of a culture or a portion of that culture (inoculum) to fresh nutrient medium. [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] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Supraspinal: Above the spinal column or any spine. [NIH] Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symptomatology: 1. That branch of medicine with treats of symptoms; the systematic discussion of symptoms. 2. The combined symptoms of a disease. [EU] Synapse: The region where the processes of two neurons come into close contiguity, and the nervous impulse passes from one to the other; the fibers of the two are intermeshed, but, according to the general view, there is no direct contiguity. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synaptic Transmission: The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors. These activated receptors modulate ion channels and/or secondmessenger systems to influence the postsynaptic cell. Electrical transmission is less common in the nervous system, and, as in other tissues, is mediated by gap junctions. [NIH] Systemic: Affecting the entire body. [NIH] Telencephalon: Paired anteriolateral evaginations of the prosencephalon plus the lamina terminalis. The cerebral hemispheres are derived from it. Many authors consider cerebrum a synonymous term to telencephalon, though a minority include diencephalon as part of the cerebrum (Anthoney, 1994). [NIH]
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Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [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] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Topical: On the surface of the body. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Translating: Conversion from one language to another language. [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] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Triazolam: A short-acting benzodiazepine used in the treatment of insomnia. Some countries temporarily withdrew triazolam from the market because of concerns about adverse reactions, mostly psychological, associated with higher dose ranges. Its use at lower doses with appropriate care and labeling has been reaffirmed by the FDA and most other countries. [NIH] Tubercle: A rounded elevation on a bone or other structure. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the
Dictionary 91
"personal unconscious". [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [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] Vasodilator: An agent that widens blood vessels. [NIH] 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] Venter: Belly. [NIH] Ventral: 1. Pertaining to the belly or to any venter. 2. Denoting a position more toward the belly surface than some other object of reference; same as anterior in human anatomy. [EU] Ventral Tegmental Area: A region in the mesencephalon which is dorsomedial to the substantia nigra and ventral to the red nucleus. The mesocortical and mesolimbic dopaminergic systems originate here, including an important projection to the nucleus accumbens. Overactivity of the cells in this area has been suspected to contribute to the positive symptoms of schizophrenia. [NIH] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] 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] 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] Wakefulness: A state in which there is an enhanced potential for sensitivity and an efficient responsiveness to external stimuli. [NIH] Whooping Cough: A respiratory infection caused by Bordetella pertussis and characterized by paroxysmal coughing ending in a prolonged crowing intake of breath. [NIH] Whooping Cough: A respiratory infection caused by Bordetella pertussis and characterized by paroxysmal coughing ending in a prolonged crowing intake of breath. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU]
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Gamma Hydroxybutyrate
Xenograft: The cells of one species transplanted to another species. [NIH]
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INDEX A Acetone, 65, 79 Acetylcholine, 65, 82 Adaptation, 21, 65 Adenosine, 65, 69, 84 Adenylate Cyclase, 65, 75 Adjustment, 65 Adrenal Cortex, 65, 72 Adrenergic, 65, 73, 74, 89 Adverse Effect, 65, 87 Affinity, 18, 38, 65, 67, 88 Agonist, 5, 17, 23, 65, 67, 69, 73, 80 Alcohol Dehydrogenase, 8, 18, 66 Alertness, 19, 66, 69 Algorithms, 66, 68 Alkaline, 66, 69 Alkaloid, 66, 69, 70, 81 Allergen, 66, 87 Alternative medicine, 42, 66 Amino acid, 14, 66, 67, 76, 77, 83, 85, 87, 89, 90 Amino Acid Sequence, 66, 67, 76 Ammonia, 66, 76 Amphetamine, 4, 7, 38, 66, 72 Analgesic, 66, 69, 81, 82 Anatomical, 16, 66, 78, 81 Anesthesia, 29, 66, 72, 79 Anesthetics, 31, 66, 68, 74 Animal model, 11, 67 Antagonism, 17, 67, 69, 80 Antibiotic, 67, 83 Antibodies, 38, 67, 77, 84 Antibody, 65, 67, 71, 77, 78, 87, 88 Anticonvulsants, 67, 68 Antidote, 8, 67 Antiepileptic, 14, 67 Antigen, 65, 67, 71, 77, 78, 81, 87 Antihypertensive, 67, 75 Anxiety, 11, 67 Arterial, 13, 67, 85 Arteries, 67, 69, 72, 80 Artery, 67, 72 Aseptic, 67, 89 Aspartate, 14, 67, 79, 84 Assay, 4, 18, 67, 78 Astrocytes, 14, 67, 81 B Baclofen, 5, 11, 35, 67
Bacteria, 67, 68, 71, 80, 81, 84, 90 Bacterial Physiology, 65, 68 Bactericidal, 68, 74 Bacteriophage, 68, 90 Barbiturates, 11, 68, 87 Basal Ganglia, 68, 82 Benzene, 68 Benzodiazepines, 11, 68 Bile, 68, 80, 88 Biochemical, 7, 8, 31, 68, 87 Biosynthesis, 68, 75 Biotechnology, 21, 42, 49, 68 Biotransformation, 8, 68 Bladder, 68, 91 Blood Coagulation, 68, 69 Blood pressure, 11, 67, 68, 78, 88 Blood vessel, 68, 69, 88, 91 Body Fluids, 69, 88 Bronchiseptica, 69, 83 Buprenorphine, 7, 69 Butyric Acid, 14, 69 C Caffeine, 5, 69 Calcium, 15, 69, 71, 88 Calcium Channels, 15, 69 Carbohydrate, 69, 76, 77 Carcinogenic, 68, 69, 85, 88 Cardiac, 13, 21, 69, 74, 81, 88 Cardiovascular, 4, 13, 22, 66, 69, 87 Case report, 31, 69 Catabolism, 18, 69 Catecholamine, 70, 73 Caudal, 70, 82 Caudate Nucleus, 70, 82 Cell, 15, 19, 65, 68, 69, 70, 71, 72, 74, 75, 76, 78, 79, 80, 81, 82, 84, 85, 86, 89, 90 Cell membrane, 69, 70, 76, 84 Central Nervous System, 15, 65, 66, 68, 69, 70, 72, 76, 77, 80, 81, 87 Cerebral, 16, 68, 70, 72, 74, 85, 89 Cerebral Cortex, 16, 70, 74 Cerebrum, 70, 89 Chromosomal, 70, 84 Chronic, 4, 6, 11, 12, 13, 16, 19, 24, 69, 70, 78, 88 Clinical Medicine, 70, 85 Clinical trial, 3, 10, 49, 70, 86 Cloning, 68, 70
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Gamma Hydroxybutyrate
Coca, 70 Cocaine, 13, 21, 38, 70 Collagen, 66, 70, 84 Complement, 71, 87 Complementary and alternative medicine, 29, 33, 71 Complementary medicine, 29, 71 Computational Biology, 49, 71 Conjugation, 68, 71 Consciousness, 16, 66, 72, 73, 85 Contraindications, ii, 72 Convulsions, 21, 72, 78 Coordination, 6, 72 Coronary, 72, 80 Coronary Thrombosis, 72, 80 Cortex, 11, 72, 86 Cortical, 72, 75, 87 Cortisol, 19, 72 Cultured cells, 15, 72 Curare, 72, 81 Curative, 72, 90 Cyclic, 10, 65, 69, 72, 75 D Data Collection, 72, 75 Delirium, 12, 72 Delusions, 72, 85 Dendrites, 72, 82 Dextroamphetamine, 66, 72, 80 Diagnostic procedure, 37, 42, 73 Digestion, 68, 73, 80, 88 Direct, iii, 13, 70, 73, 77, 80, 86, 89 Discrimination, 4, 6, 12, 17, 73 Disinfectant, 73, 74 Disorientation, 72, 73 Disposition, 10, 73 Dissociation, 65, 73 Distal, 73, 74 Diuresis, 69, 73 Diurnal, 19, 73 Dopamine, 10, 66, 70, 73, 81, 82 Drug Combinations, 15, 73 Drug Tolerance, 73, 90 E Efficacy, 4, 6, 24, 73 Electrode, 7, 74 Electrolyte, 72, 74, 85, 88 Electrophysiological, 7, 16, 74 Endocrine System, 74, 82 Endogenous, 7, 15, 73, 74 Endorphins, 74, 82 Enkephalins, 74, 82 Environmental Health, 48, 50, 74
Enzymatic, 8, 18, 38, 66, 69, 71, 74 Enzyme, 8, 18, 65, 66, 74, 75, 81, 89, 91 Epidemic, 10, 74 Epinephrine, 65, 73, 74, 82, 90 Ergot, 74, 80 Erythrocytes, 74, 87 Ethanol, 7, 10, 14, 18, 35, 66, 74, 75 Evoke, 74, 88 Excitability, 7, 74 Excitation, 75, 82 Excitatory, 7, 14, 16, 68, 75, 76 Exhaustion, 67, 75 Exogenous, 19, 68, 74, 75 Extracellular, 10, 67, 75, 88 Extraction, 18, 75 Extrapyramidal, 73, 75 F Family Planning, 49, 75 Fat, 14, 69, 75, 79, 80 Fermentation, 66, 75 Fixation, 75, 87 Flame Ionization, 18, 75 Flatus, 75, 76 Flunitrazepam, 6, 75 Focus Groups, 10, 75 Forearm, 69, 75 Forskolin, 15, 75 G Gamma-hydroxybutyrate, 6, 8, 11, 15, 16, 17, 18, 20, 30, 31, 75 Gap Junctions, 76, 89 Gas, 18, 66, 75, 76, 77, 82 Gastric, 10, 76 Gastrin, 76, 77 Gastrointestinal, 15, 74, 76, 87, 89 Gastrointestinal tract, 74, 76, 87 Gene, 31, 68, 76 Gene Expression, 31, 76 Genetic Code, 76, 82 Gland, 65, 76, 83, 84, 87, 88 Glottis, 76, 84 Glucose, 19, 76, 78, 79 Glucose tolerance, 19, 76 Glucose Tolerance Test, 76 Glutamate, 14, 76 Glutamic Acid, 76, 82 Glutamine, 14, 76 Glycerol, 69, 76, 84 Glycine, 66, 77, 82 Glycoproteins, 69, 77, 79 Governing Board, 77, 85
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H Hallucinogen, 77, 80, 84 Haptens, 65, 77 Headache, 69, 77, 78 Hepatic, 72, 76, 77 Heredity, 76, 77 Heterogeneity, 65, 77 Homologous, 77, 87, 89 Hormone, 19, 72, 74, 76, 77, 79 Hybrid, 15, 77 Hydrogen, 66, 69, 75, 77, 81, 83 Hydrogenation, 68, 77 Hydrolysis, 68, 77, 85 Hydroxyproline, 66, 70, 77 Hypersensitivity, 66, 77, 87 Hypnotic, 9, 11, 30, 32, 77 Hypoglycaemia, 72, 78 Hypotension, 72, 78 Hypothermia, 21, 78 Hypoxia, 72, 78 I Immune response, 67, 77, 78, 87, 89, 91 Immunization, 78, 87 Immunoassay, 38, 78 Immunologic, 78 Immunology, 65, 78 Impairment, 4, 5, 72, 78, 80, 85 In vitro, 7, 78 In vivo, 8, 16, 78 Incubation, 78, 83 Incubation period, 78, 83 Infarction, 72, 78, 80 Infection, 67, 72, 78, 83, 89, 91 Infusion, 6, 78 Ingestion, 16, 76, 78, 84 Inhalation, 78, 84 Inoculum, 79, 89 Inotropic, 73, 79 Insomnia, 11, 79, 90 Insulin, 19, 76, 79 Insulin-dependent diabetes mellitus, 79 Intestinal, 76, 79 Intestines, 76, 79 Intoxication, 14, 16, 23, 24, 32, 72, 79, 91 Intracellular, 69, 78, 79, 85 Intraocular, 75, 79 Intraocular pressure, 75, 79 Intravenous, 15, 78, 79 Intrinsic, 7, 65, 79 Involuntary, 79, 81, 86, 88 Ion Channels, 67, 79, 89 Ion Exchange, 79, 88
Ions, 69, 73, 74, 77, 79 K Kb, 48, 79 Ketamine, 20, 38, 79, 84 Ketone Bodies, 14, 65, 79 Kinetic, 15, 79 L Latent, 20, 79 Lipid, 76, 79, 80 Liver, 18, 68, 76, 77, 80 Locomotion, 8, 11, 80, 84 Locomotor, 18, 80 Lymphoid, 67, 80 Lysergic acid, 20, 38, 80 Lysergic Acid Diethylamide, 20, 80 M Manic, 80, 85 Mediate, 9, 10, 73, 80 MEDLINE, 49, 80 Meiosis, 80, 89 Membrane, 7, 15, 67, 70, 71, 74, 79, 80, 83, 84 Memory, 72, 80 Meninges, 70, 80 Mental, iv, 3, 48, 50, 70, 72, 73, 80, 85, 86, 87 Mental Disorders, 80, 85 Mental Health, iv, 3, 48, 50, 80, 86 Mesolimbic, 80, 91 Metabolite, 38, 68, 80 Methamphetamine, 20, 38, 80 MI, 63, 80 Microbe, 80, 90 Microbiology, 65, 81 Microglia, 67, 81 Modeling, 10, 81 Modification, 66, 81 Molecular, 15, 32, 38, 49, 51, 68, 71, 81, 90 Molecule, 38, 67, 71, 73, 75, 77, 81, 83, 84, 86, 91 Monoamine, 66, 73, 81 Morphine, 4, 7, 38, 69, 81, 82 Motor Activity, 72, 81 Motor nerve, 81 Muscle relaxant, 4, 81 Muscle tension, 81 Myocardium, 80, 81 N Naltrexone, 15, 81 Narcolepsy, 6, 9, 10, 13, 19, 32, 72, 81 Narcotic, 81 Necrosis, 78, 80, 81
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Gamma Hydroxybutyrate
Nerve, 13, 65, 66, 72, 81, 82, 85, 88, 90 Nervous System, 66, 70, 81, 82, 83, 89 Networks, 5, 21, 82 Neuroblastoma, 15, 82 Neuroendocrine, 19, 82 Neuromuscular, 8, 65, 82 Neuronal, 7, 15, 16, 69, 82 Neurons, 15, 16, 70, 72, 75, 81, 82, 89 Neurotransmitter, 9, 14, 15, 65, 66, 73, 76, 77, 79, 82, 89 Nitrogen, 66, 75, 76, 82 Norepinephrine, 65, 73, 82 Nucleic acid, 38, 76, 82 Nucleus, 7, 10, 72, 80, 82, 85, 91 Nucleus Accumbens, 7, 10, 82, 91 Nursing Care, 32, 82 O Opiate, 13, 81, 82 Opium, 38, 81, 82 Osmolality, 24, 82 Osmoles, 82, 83 Osmotic, 83 Overdose, 8, 16, 22, 23, 83 Oxidation, 68, 83 Oxidation-Reduction, 68, 83 P Palliative, 83, 90 Pancreas, 79, 83 Paroxysmal, 83, 91 Particle, 83, 90 Patch, 7, 83 Pathogenesis, 32, 83 Penicillin, 67, 83 Peptide, 66, 83, 85 Perception, 10, 83, 87 Peripheral Nervous System, 74, 82, 83, 89 Pertussis, 15, 83, 91 Pharmacokinetic, 19, 84 Pharmacologic, 8, 66, 75, 84, 90 Phencyclidine, 38, 84 Phospholipids, 75, 84 Phosphorus, 69, 84 Physiologic, 65, 68, 84, 86 Physiology, 74, 84 Pituitary Gland, 75, 84 Plants, 66, 70, 76, 82, 84, 90 Plasma, 15, 67, 70, 76, 84 Plasma cells, 67, 84 Plasmid, 18, 84, 91 Platelet Aggregation, 75, 84 Pleomorphic, 82, 84 Pneumonia, 72, 84
Poisoning, 17, 23, 26, 29, 72, 74, 79, 84 Polypeptide, 66, 70, 85 Postsynaptic, 11, 85, 89 Potassium, 11, 85 Potentiation, 7, 85 Practice Guidelines, 50, 85 Preclinical, 11, 85 Precursor, 14, 73, 74, 82, 85, 90 Presynaptic, 82, 85, 89 Progression, 67, 85 Progressive, 12, 73, 81, 85, 86 Projection, 7, 82, 85, 86, 91 Promoter, 32, 85 Prophase, 85, 89 Protein S, 68, 76, 85 Proteins, 15, 66, 67, 70, 71, 76, 81, 82, 83, 84, 85, 87 Psychiatric, 80, 85, 88 Psychic, 80, 85, 87 Psychoactive, 13, 22, 24, 85, 91 Psychomotor, 72, 85 Psychosis, 12, 85, 86 Psychotomimetic, 66, 73, 86 Public Health, 5, 10, 12, 20, 50, 86 Public Policy, 49, 86 Pulmonary, 21, 69, 86, 91 Pulmonary Artery, 69, 86, 91 Punishment, 12, 86 R Randomized, 6, 73, 86 Reagent, 18, 86 Reality Testing, 85, 86 Receptor, 8, 9, 10, 11, 15, 16, 17, 18, 65, 67, 73, 86, 87 Recombinant, 86, 91 Rectum, 75, 76, 86 Red Nucleus, 86, 91 Refer, 1, 71, 74, 75, 80, 85, 86, 90 Reflex, 8, 86 Regimen, 73, 86 Relaxant, 75, 86 Reliability, 18, 86 Renal failure, 72, 86 Response rate, 4, 86 Risk factor, 10, 86 Ritalin, 38, 86 S Saline, 6, 17, 87 Schizoid, 87, 91 Schizophrenia, 13, 87, 91 Schizotypal Personality Disorder, 87, 91 Screening, 18, 38, 70, 87
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Secretion, 19, 79, 81, 87 Secretory, 87, 89 Sedative, 4, 9, 11, 16, 32, 87 Sedatives, Barbiturate, 68, 87 Seizures, 14, 15, 16, 67, 72, 83, 87 Sensitization, 4, 87 Sensor, 38, 39, 87 Serologic, 78, 87 Serotonin, 80, 82, 87 Serum, 24, 71, 87 Shock, 87, 90 Side effect, 7, 65, 87, 90 Signs and Symptoms, 12, 88 Sleep Deprivation, 19, 88 Small intestine, 77, 79, 88 Smooth muscle, 69, 75, 81, 88, 89 Sneezing, 83, 88 Sodium, 15, 24, 30, 88 Sodium-Calcium Exchanger, 15, 88 Solvent, 65, 68, 74, 77, 82, 83, 88 Spasmodic, 84, 88 Specialist, 55, 88 Species, 72, 74, 77, 80, 88, 91, 92 Specificity, 5, 15, 38, 65, 69, 88 Spinal cord, 67, 70, 80, 82, 83, 86, 88, 89 Steroid, 72, 88 Stimulant, 5, 18, 66, 69, 72, 80, 88 Stimulus, 4, 6, 9, 11, 17, 74, 75, 79, 86, 88, 90 Stomach, 76, 77, 79, 88 Stress, 19, 70, 72, 88 Striatum, 82, 89 Subclinical, 78, 87, 89 Subculture, 20, 89 Substance P, 80, 87, 89 Substrate, 15, 31, 89 Suppression, 19, 89 Supraspinal, 68, 89 Sympathetic Nervous System, 89 Sympathomimetic, 13, 66, 72, 73, 74, 80, 82, 89 Symptomatology, 17, 89 Synapse, 65, 85, 89, 90 Synaptic, 7, 16, 82, 89 Synaptic Transmission, 16, 89 Systemic, 69, 72, 74, 78, 89
T Telencephalon, 68, 70, 89 Therapeutics, 10, 30, 90 Threshold, 74, 90 Tissue, 15, 67, 69, 70, 73, 74, 78, 80, 81, 82, 84, 87, 88, 90 Tolerance, 4, 7, 11, 19, 69, 76, 90 Tooth Preparation, 65, 90 Topical, 74, 90 Toxic, iv, 68, 71, 72, 90 Toxicity, 8, 13, 16, 19, 22, 90 Toxicology, 18, 24, 31, 32, 50, 90 Toxin, 15, 90 Transduction, 15, 90 Transfection, 68, 90 Translating, 5, 90 Translation, 66, 90 Transmitter, 65, 67, 73, 79, 82, 90 Trauma, 23, 72, 77, 81, 90 Triazolam, 5, 90 Tubercle, 82, 90 Tyrosine, 73, 90 U Unconscious, 66, 90 Urethra, 91 Urine, 10, 18, 68, 73, 79, 91 V Vasodilator, 73, 91 Vector, 18, 90, 91 Vein, 79, 91 Venter, 91 Ventral, 7, 82, 91 Ventral Tegmental Area, 7, 91 Ventricle, 70, 82, 86, 91 Veterinary Medicine, 49, 91 Viral, 90, 91 Virulence, 90, 91 Virus, 68, 90, 91 Vitro, 91 Vivo, 91 W Wakefulness, 72, 91 Whooping Cough, 84, 91 Withdrawal, 6, 11, 12, 13, 14, 16, 19, 22, 23, 72, 91 X Xenograft, 67, 92
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Gamma Hydroxybutyrate
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100
Gamma Hydroxybutyrate
