BARBITURATES 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., 1960Barbiturates: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-84348-1 1. Barbiturates-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 barbiturates. 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 BARBITURATES .......................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Barbiturates................................................................................... 5 E-Journals: PubMed Central ....................................................................................................... 16 The National Library of Medicine: PubMed ................................................................................ 17 CHAPTER 2. NUTRITION AND BARBITURATES ................................................................................ 29 Overview...................................................................................................................................... 29 Finding Nutrition Studies on Barbiturates ................................................................................. 29 Federal Resources on Nutrition ................................................................................................... 31 Additional Web Resources ........................................................................................................... 32 CHAPTER 3. ALTERNATIVE MEDICINE AND BARBITURATES .......................................................... 33 Overview...................................................................................................................................... 33 National Center for Complementary and Alternative Medicine.................................................. 33 Additional Web Resources ........................................................................................................... 35 General References ....................................................................................................................... 38 CHAPTER 4. DISSERTATIONS ON BARBITURATES ............................................................................ 39 Overview...................................................................................................................................... 39 Dissertations on Barbiturates ...................................................................................................... 39 Keeping Current .......................................................................................................................... 39 CHAPTER 5. PATENTS ON BARBITURATES....................................................................................... 41 Overview...................................................................................................................................... 41 Patents on Barbiturates................................................................................................................ 41 Patent Applications on Barbiturates............................................................................................ 57 Keeping Current .......................................................................................................................... 61 CHAPTER 6. BOOKS ON BARBITURATES .......................................................................................... 63 Overview...................................................................................................................................... 63 Book Summaries: Online Booksellers........................................................................................... 63 Chapters on Barbiturates ............................................................................................................. 64 CHAPTER 7. PERIODICALS AND NEWS ON BARBITURATES ............................................................ 65 Overview...................................................................................................................................... 65 News Services and Press Releases................................................................................................ 65 Academic Periodicals covering Barbiturates................................................................................ 67 CHAPTER 8. RESEARCHING MEDICATIONS .................................................................................... 69 Overview...................................................................................................................................... 69 U.S. Pharmacopeia....................................................................................................................... 69 Commercial Databases ................................................................................................................. 70 APPENDIX A. PHYSICIAN RESOURCES ............................................................................................ 75 Overview...................................................................................................................................... 75 NIH Guidelines............................................................................................................................ 75 NIH Databases............................................................................................................................. 77 Other Commercial Databases....................................................................................................... 79 APPENDIX B. PATIENT RESOURCES ................................................................................................. 81 Overview...................................................................................................................................... 81 Patient Guideline Sources............................................................................................................ 81 Finding Associations.................................................................................................................... 83 APPENDIX C. FINDING MEDICAL LIBRARIES .................................................................................. 85 Overview...................................................................................................................................... 85 Preparation................................................................................................................................... 85 Finding a Local Medical Library.................................................................................................. 85
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Medical Libraries in the U.S. and Canada ................................................................................... 85 ONLINE GLOSSARIES.................................................................................................................. 91 Online Dictionary Directories ..................................................................................................... 93 BARBITURATES DICTIONARY ................................................................................................. 95 INDEX .............................................................................................................................................. 149
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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 barbiturates 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 barbiturates, 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 barbiturates, 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 barbiturates. 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 barbiturates, 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 barbiturates. 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 BARBITURATES Overview In this chapter, we will show you how to locate peer-reviewed references and studies on barbiturates.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and barbiturates, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “barbiturates” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •
Dental and Medical Considerations of Patients with Renal Disease Source: CDA Journal. Journal of the California Dental Association. 26(10): 762-770. October 1998. Contact: Available from California Dental Association (CDA). 1201 K Street, Sacramento, CA 95814. (916) 443-0505. Summary: Often a dentist will have a patient with a complicated medical condition that needs to be taken into consideration when providing dental care. This article offers a detailed discussion of the medical and dental considerations of patients with renal (kidney) disease. The authors first briefly review normal renal physiology, then define chronic renal disease and end stage renal disease (ESRD) and their treatments. The authors then cover complications of ESRD, including fluid and electrolyte disturbances,
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metabolic acidosis, anemia, bleeding disorders, immunocompromise (including that induced by drug therapy for transplant patients), viral infections, endocrine metabolic disturbances, cardiovascular disease, gastrointestinal abnormalities, neurologic abnormalities, and dermatologic or oral manifestations of kidney disease. Another section discusses drug indications for these patients, including antibiotics, analgesics, antihistamines, decongestants, barbiturates, and sedatives. For the patient with chronic renal failure and ESRD, the goal for treatment should be to establish the best oral hygiene possible and to remove all sources of infection. In the transplant patient, dental hygiene is crucial because these patients are even more susceptible to the highly morbid consequences of infection. Dental procedures are best performed on nondialysis days for two reasons: conflicting scheduling problems and the use of heparin during dialysis. 3 tables. 38 references. •
Oral Management of the Patient with End-Stage Liver Disease and the Liver Transplant Patient Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 86(1): 55-64. July 1998. Contact: Available from Mosby, Inc. 11830 Westline Industrial Drive, St. Louis, MO 63146-3318. (800) 453-4351 or (314) 453-4351. Summary: This article addresses the oral management of the patient with end stage liver disease and the liver transplant patient. The authors emphasize that the patient with end stage liver disease, who is in need of a liver transplant, should have a pretransplant dental evaluation. Such a patient faces lifelong immunosuppression with an increased risk of infection. The article discusses both the need for control of oral diseases before liver transplantation and guidelines for oral care in the immediately postoperative and long term transplant patient. Specific indications for antibiotic prophylaxis and antibiotic regimens are presented; in addition, the adverse reactions and side effects of immunosuppressant drugs are discussed. The authors review pertinent drug interactions related to the dental management of patients with end stage liver disease, and present specific management recommendations. Specific drugs covered include cyclosporine, FK 506, prednisone, monoclonal antibody (OKT3), azathioprine, antilymphocyte globulin (ATG), morphine, codeine, nonsteroidal antiinflammatory drugs (NSAIDs), sedatives and anxiolytic drugs, local anesthetics, barbiturates, and propofol. 5 tables. 95 references. (AA-M).
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Management of the Psychotic Patient Source: Oral and Maxillofacial Clinics of North America. 10(3): 457-464. August 1998. Contact: Available from W.B. Saunders. Periodicals Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452. Website: www.wbsaunders.com. Summary: This article reviews the pharmacologic management of the psychotic patient, to familiarize oral and maxillofacial surgeons with the care of these patients. The author notes that the trend to outpatient care extends to the psychiatric patient and more health care providers will be faced with the care of this patient population. The author reviews potential drug interactions and clinical considerations for patients already under maintenance therapy. The article covers antipsychotic agents, mood disorders, HCAs (including tricyclic drugs), MAOIs (derivatives of hydrazine or amphetamine), SSRIs (antidepressants), bipolar disorder, and antianxiety agents, specifically benzodiazepines, barbiturates, and buspirone. The emphasis in each section is on pharmacodynamics, drug interactions, and anesthetic concerns. 3 tables. 25 references.
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Federally Funded Research on Barbiturates The U.S. Government supports a variety of research studies relating to barbiturates. 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 barbiturates. 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 barbiturates. The following is typical of the type of information found when searching the CRISP database for barbiturates: •
Project Title: ADENOSINE AND TRAUMATIC BRAIN INJURY Principal Investigator & Institution: Kochanek, Patrick M.; Associate Professor; Critical Care Medicine; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 02-AUG-1999; Project End 31-JUL-2003 Summary: Traumatic brain injury (TBI) is an enormous public heath problem; however, targeted therapies are lacking. After severe TBI, ischemia and energy failure frequently occur. Adenosine is a purine nucleotide that acts as a powerful endogenous neuroprotectant during ischemia-induced energy failure by decreasing neuronal metabolism and increasing cerebral blood flow (CBF), among other mechanisms. These effects are mediated through interaction of adenosine with specific receptors. The synergistic effects of increasing CBF and decreasing metabolism suggest an important neuroprotectant role for adenosine after TBI, particularly during secondary insults. Further augmenting the effects of adenosine in brain may reduce neuronal damage. Two strategies to achieve this are particularly relevant to TBI and this application, namely, 1) the inhibition of adenosine metabolism or 2) the local administration of adenosine analogs. Defining four Specific Aims, we will use an established rat model of TBI and applying cerebral microdialysis, contemporary MRI tools, functional outcome testing, and histology, we will first determine the magnitude of the adenosine response (brain interstital levels of adenosine and purine degradation products) to experimental TBI. We will then examine effects of these two defined strategies of augmenting adenosine effects both on key mechanisms of secondary damage (excitotoxicity [brain interstitial levels of glutamate, CBF by perfusion MRI, and Ca++ accumulation in brain by Mn++contrast-enhanced MRI) and both functional and histopathological outcome. Finally, in a fifth Specific Aim, we will bridge bench to bedside by using cerebral microdialysis methods to define the participation of adenosine (and its relationship to CBF and excitotoxicity) after severe TBI in humans, during the application of contemporary therapeutic interventions (CSF drainage, mannitol, hyperventilation, and barbiturates) in the treatment of intracranial hypertension. If successful, these studies will set the
2 Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
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stage for a clinical trial, and provide important mechanistic information on the role of adenosine after TBI in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANESTHETIC EFFECTS ON GLYCINE AND GABA-A RECEPTORS Principal Investigator & Institution: Mihic, S John.; Associate Professor; Neurobiology; University of Texas Austin 101 E. 27Th/Po Box 7726 Austin, Tx 78712 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 30-JUN-2005 Summary: (provided by applicant): The overall objective of the proposed work in this developmental grant application is to further understanding of the mechanisms of ligand-gated ion channel activation, desensitization and allosteric modulator action. To this end we propose the electrophysiological characterization of newly-discovered mutants of glycine alpha1 and GABA-A alpha1 and beta2 receptor subunits. Single amino acid mutations of these subunits have been identified that result in channels that open spontaneously and desensitize in the absence of agonist. Tonic opening is revealed by a reversible strychnine- or bicuculline-induced outward current. Tonically-opening glycine and GABA-A receptors will be transiently expressed in mammalian HEK 293 cells and characterized using a fast drug application system. The use of a fast drug exchange system will allow for an accurate assessment of rates of channel opening, closing and desensitization after applying GABA-A and glycine receptor agonists or antagonists to receptors composed of wild-type or mutated subunits. Single channel outside-out patch recordings of our tonically-open channels are hypothesized to display bursts of channel opening events separated by quiescent, desensitized periods. We will then take advantage of the tonic opening and desensitization that occur spontaneously in these mutated receptors to clarify the molecular mechanisms underlying the actions of allosteric modulators. GABA and glycine receptor function is allosterically modulated by numerous classes of agents such as the barbiturates, benzodiazepines and steroidal and volatile anesthetics. Using the receptor mutants we have already created, and new mutants we propose to make, we will test the hypothesis that modulatory concentrations of these agents affect the functioning of tonically-open GABA-A and glycine receptors in the absence of agonist binding to the neurotransmitter receptor binding site, allowing us to dissociate modulator-induced stabilization of open channel states and effects on desensitization from their effects on increasing the affinity of neurotransmitter for its receptor. The work proposed will increase understanding not only of basic receptor/channel processes, but also shed insight into the molecular mechanisms of receptor modulation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BENZODIAZEPINE-INDUCED GABAA RECEPTOR PLASTICITY Principal Investigator & Institution: Olsen, Richard W.; Professor; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002 Summary: The GABA inhibitory synaptic system plays a major role in the central nervous system and is implicated in human neurological and psychiatric disorders such as epilepsy, stress, anxiety and panic disorders, sleep disorders, and drug dependence, especially to benzodiazepines and ethanol. The major postsynaptic GABA receptors involved in rapid inhibitory neurotransmission are the GABA/A receptors (GABA). GABAR proteins are subject to regulation at the level of transcription, translation, assembly, cell targeting, and the functional level. Endogenous regulation includes
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modulation by phosphorylation, zinc ions, and neuroactive steroids. GABAR are the known target of numerous clinically relevant drugs, including anti-epileptic antianxiety, and sedative/hypnotic/aesthetic agents. These include the widely used benzodiazepines, barbiturates, and possibly alcohol. GABAR are widely accepted as the major candidate molecular target of general anesthetic action. Their predominant role in the brain makes GABA likely players in the normal plasticity mechanisms that accompany ordinary and extraordinary experiences. By subjecting rats, or in some cases, cells, to somewhat extraordinary experiences that are considered to involve GABAR, we will investigate whether plastic changes in GABAR occur and the molecular and cellular mechanisms of the long-term modifications. In particular, chronic exposure of rats to benzodiazepines, but probably an elevation of GABAR function, leads to tolerance, especially to the anti-epileptic actions of these drugs. Tolerance is accompanied by a reduced GABAR function, reduced enhancement of GABAR function by benzodiazepines, and uncoupling of GABA- benzodiazepine binding measured in vitro. Tolerance to benzodiazepines can be mimicked in cells expressing recombinant GABAR that lack normal transcriptional control, and can be reversed rapidly by exposure in rats and in cells by exposure to the benzodiazepine antagonist flumazenil. This strongly suggests that the tolerance and reversal result from a physicochemical modification of the GABAR protein itself. This project will attempt to unearth this molecular mechanisms of plasticity. Ultimately therapeutic strategies could be based on our studies, aimed rationally at preventing the unwanted or pathological alterations in GABA/A receptors characteristic of several neurological and psychiatric disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DIRECT INTERACTION BETWEEN GABA-A AND GABA-B RECEPTORS Principal Investigator & Institution: Hall, Randy A.; Pharmacology; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2008 Summary: (provided by applicant): Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the mammalian brain. GABA exerts its physiological actions in the brain via the activation of two distinct types of receptor: GABA-A receptors, which are ligand-gated ion channels, and GABA-B receptors, which are G proteincoupled receptors. GABA-A and GABA-B receptors are known to exhibit forms of cross-talk and mutual regulation for which no mechanism has been defined. This project aims to study the importance of a novel and direct interaction found between the GABA-BR1 receptor and the gamma2 subunit of the GABA-A receptor. This physical association may provide a mechanism to allow for direct cross-talk between GABA-A and GABA-B receptors. The structural determinants and physiological significance of this interaction, however, are completely unknown at the present time. The specific regions of GABA-BR1 and the gamma2 subunit of the GABA-A receptor involved in mediating their interaction will be elucidated using a mutagenesis approach in combination with both co-immunoprecipitation and fusion protein pull-down studies. The effects of GABA-A receptor association on GABA-B receptor pharmacology will be studied in ligand binding assays, and GABA-A receptor modulation of GABA-B receptor signaling and internalization will also be analyzed. Furthermore, GABA-B receptor regulation of GABA-A receptor pharmacology, channel activity and phosphorylation will be examined, with an emphasis on determining the functional importance of the direct interaction between GABA-BR1 and the GABA-A receptor gamma2 subunit. These studies will shed new light on the regulation of cellular
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responses to GABA and the molecular basis for cross-talk between GABA-A and GABAB receptors. Such information is critical for a comprehensive understanding of pharmaceuticals acting on GABA receptors. GABA-A receptors are the targets for such commonly prescribed therapeutic drugs as benzodiazepines and barbiturates, while the more recently-identified GABA-B receptors represent excellent potential targets for novel therapeutic drugs aimed at treating disorders such as schizophrenia, epilepsy, anxiety, chronic pain and depression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DISTINCTIVE INTEROCEPTIVE EFFECTS OF ALPHA 1 SELECTIVE GABA MODULATOR ZOLPIDEM Principal Investigator & Institution: Rowlett, James K.; Assistant Professor; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 30-APR-2003 Summary: Zolpidem (Ambien ) is a commonly prescribed sleep-aid that exhibits selectivity for benzodiazepine (BZ)/GABAA receptors containing the alpha-1 subunit Previous studies have suggested that zolpidem has a characteristic profile of subjective effects that differ from those of conventional BZ agonists The present study assessed the ability of BZs and barbiturates, which typically share interoceptive effects with BZs, to reproduce the effects of zolpidem in squirrel monkeys trained to discriminate zolpidem from vehicle The effects of zolpidem also were assessed in squirrel monkeys trained to discriminate another sleep-aid, triazolam (Halcion ) Under test conditions, zolpidem engendered a dose-dependent increase in zolpidem-lever responding, reaching an average maximum of r80% Triazolam and diazepam also engendered r80% zolpidemlever responding However, other BZ agonists including chlordiazepoxide and lorazepam, as well as the barbiturates pentobarbital, bar bital, and methohexital, engendered maximums of only 20-70% zolpidem-lever responding up to doses that markedly reduced response rate In contrast, zolpidem, chlordiazepoxide and lorazepam substituted fully in monkeys trained to discriminate triazolam using a similar procedure These results suggest that zolpidem's selectivity for the alpha-1 subunit of the BZ/GABAA receptor complex confers a profile of interoceptive effects that is unique compared to typical BZ agonists Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DRUGS OF ABUSE: NEURONAL SURVIVAL AND SIGNALING Principal Investigator & Institution: Moulder, Krista L.; Psychiatry; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 01-FEB-2003; Project End 31-JAN-2005 Summary: (provided by applicant): The broadest objective of the proposed research is to characterize the changes in synaptic signaling that accompany increases and decrease in electrical activity. Chronic exposure to drugs of abuse such as ethanol, barbiturates, and benzodiazepines causes a downregulation in electrical activity, which ultimately leads to neuronal death. The goal of Aim 1 is to determine whether this decrease in neuronal activity results in reduced neurotransmitter release because of drug effects on Ca2+ currents, or in enhanced neurotransmitter release through initiation of homeostatic mechanisms. Such changes in synaptic signaling could either lessen or intensify the effects of drugs of abuse on neuronal survival. The goal of Aim 2 is to determine the effects on synaptic signaling caused by mimicking increased electrical activity with K+ depolarization. Preliminary data indicate that depolarization curtails development of
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glutamatergic synapses, while leaving inhibitory currents intact. Experiments will be conducted to distinguish whether a presynaptic and a postsynaptic mechanism accounts for this effect of K+ on excitatory currents. Both Aim 1 and Aim 2 will utilize whole-cell, patch-clamp techniques in a hippocampal microculture paradigm, which will facilitate examination of synaptic electrophysiology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RECEPTORS
GENERAL
ANESTHETIC
INTERACTIONS
WITH
GABA-A
Principal Investigator & Institution: Akabas, Myles H.; Associate Professor; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2002 Summary: (taken from the application): The gamma-aminobutyric acid Type A (GABAA) receptors form ligand-activated, anion-selective channels. They are the primary, fastacting, post-synaptic receptors for GABA, the major inhibitory neurotransmitter in the central nervous system. Current hypotheses suggest that GABA-A receptors may be a primary target for the actions of many general anesthetics. At low concentrations general anesthetics, such as propofol, etomidate, barbiturates and enflurane, potentiate GABA-induced currents, whereas at higher concentrations these anesthetics directly activate GABA-A receptors but do not appear to bind in the GABA binding sites. In order to understand the molecular basis of anesthetic action it is necessary to define the binding sites for these drugs, the conformational changes that occur following binding and the structure of the binding site. Mutations in the alpha-1 subunit of Ser270 (M2) and Ala291 (M3), residues near the extracellular ends of the M2 and M3 membranespanning segments, altered the efficacy of the inhaled ether anesthetics (enflurane and isoflurane) to potentiate GABA-induced currents. Whereas, mutations of the aligned residues in the beta subunits altered the efficacy of intravenous anesthetics (etomidate, barbiturates and perhaps propofol) to potentiate GABA-induced. It is uncertain whether these residues are part of anesthetic binding sites or are part of the transduction pathway. Cysteine substituted for these residues in the alpha-1 subunit were accessible to react with the negatively charged, sulfhydryl-specific reagent, pCMBS, applied extracellularly indicating that they are on the water-accessible surface of the protein. If these residues form a binding site(s) for anesthetics then anesthetics should protect the Cys-substituted mutants from modification by pCMBS. The ability of anesthetics to protect these Cys-substitution mutants will be determined. It was previously shown that Cys substituted for six of seventeen residues in the M3 segment were accessible to react with pCMBS. Reaction at four of the six positions was state dependent, it only occurred in the presence of GABA. It will be determined whether potentiating or directly activating concentrations of anesthetics induce changes in the accessibility of M3 segment substituted Cys mutants similar to those induced by GABA. Finally, if the M2 and M3 membrane-spanning segments participate in forming an anesthetic binding site or interactions between them are important for transduction of anesthetic effects then they should be in close proximity. Disulfide bond formation will be used as a molecular ruler to determine the relative proximity, mobility and orientation of the M2 and M3 segments within a single subunit. The successful completion of this proposal could provide new insights into the binding and transduction of anesthetic effects in the GABA-A receptors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENETIC VULNERABILITY TO DRUGS OF ABUSE Principal Investigator & Institution: Buck, Kari J.; Associate Professor; Behavioral Neuroscience; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2003; Project Start 01-AUG-1989; Project End 31-MAR-2005 Summary: Quantitative trait loci (QTLs) are chromosomal regions containing genes that influence a complex trait such as drug withdrawal severity. We have established that there is a great deal of common genetic influence on withdrawal from barbiturates, benzodiazepines, nitrous oxide, and alcohol. During the current period, we have mapped several QTLs that jointly have a major influence on the severity of pentobarbital (PB) withdrawal. The three largest QTLs are on mouse chrs 1, 4 and 11. QTLs in each of these regions have also been provisionally mapped for diazepam withdrawal, and definitively mapped for ethanol withdrawal: the chr 1 QTL was also provisionally mapped for nitrous oxide withdrawal. Using congenic strains to isolate each of the three QTLs against a uniform (inbred) genetic background, we propose to continue toward the eventual identification of the genes that underlie each PB withdrawal QTL. We propose to: (1) Test congenics for the strongest PB QTLs for their pleiotropic effects on withdrawal from other drugs of abuse; (2) Produce polycongenics in different combinations to determine whether gene-gene (epistatic) interactions are additive, potentiating in some combinations, or epistatic in some other way; (3) Narrow each QTL interval from our present approximately 20 cM to approximately 1 cM using interval specific congenic strains (ISCS); (4) Scan promising candidate genes for cDNA differences between B6 and D2 genotypes by SSCP; (5) Produce polycongenics from specific donor segment (SDS) congenics produced from appropriate interval specific congenic strains, and test for epistatic interactions among QTLs, as well as QTL pleiotropisms for withdrawal from other drugs, and for other drug-related responses known to be genetically correlated with PB withdrawal severity; and (6) Start with an F2 population, screen for additional QTLs not previously ascertained and produce additional congenics to facilitate eventual cloning of the genes. 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 27706 Timing: Fiscal Year 2003; Project Start 20-SEP-2003; Project End 31-MAY-2007 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
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(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: HYPOTHERMIA DURING INTRACRANIAL ANEURYSM SURGERY Principal Investigator & Institution: Todd, Michael M.; Anesthesia; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002; Project Start 05-SEP-1999; Project End 31-MAY-2004 Summary: Aneurysmal subarachnoid hemorrhage (SAH) remains a major cause of morbidity and mortality. Since the incidence peaks in mid-life, and since many survivors are permanently damaged, the human and economic costs are immense. Much of the death and disability is the acute and delayed result of blood in the subarachnoid space (e.g. vasospasm). However, an unknown - but we believe substantial - fraction of the adverse outcomes are a complication of surgery performed to obliterate the source of bleeding; as many as 25 percent of patients who undergo craniotomy for aneurysm clipping will have a new neurologic deficit when examined 12-24hrs postoperatively. This danger is well known, and almost all surgical teams utilize some method to protect patients during surgery, including barbiturates, etomidate, steroids, mannitol or varying degrees of hypothermia. Unfortunately, in spite of the popularity of such interventions, none has ever been systematically tested in humans (other than deep hypothermia and circulatory arrest), and none are known to provide any benefit at all. Of the aforementioned therapies, we believe the best laboratory evidence supports the use of hypothermia. Our goal, therefore, is to perform a prospective, randomized clinical trial to evaluate the safety and efficacy of intraoperative hypothermia (t=33 degrees C) as a means of reducing early and long-term postoperative neurologic morbidity following surgery for clipping of intracranial aneurysm. Control patients will remain normothermic during and after surgery; in hypothermic patients, body temperature will be normalized as quickly as possible after the aneurysm clip is in place. All other aspects of pre- and postoperative care will be managed routinely. We hypothesize that hypothermia, even when limited to the intraoperative period, will result in an improvement in neurologic outcome as measured by Glasgow Outcome Scale at 3months following surgery, and will also result in more rapid improvement during the first postoperative week. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MECHANISM OF ACTION OF BENZODIAZEPINES ON GABA RECEPTORS Principal Investigator & Institution: Weiss, David S.; Professor; Neurobiology; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2003; Project Start 01-APR-1997; Project End 28-FEB-2007 Summary: (provided by applicant): Gamma aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian brain. The binding of GABA to postsynaptic GABA receptors opens a chloride-selective ion pore that is an integral component of the multimeric receptor complex. The resulting chloride flux across the cell membrane inhibits the postsynaptic neuron. Dysfunctions in GABA-mediated inhibition have been implicated in the etiology of a variety of neurological and psychological disorders. Furthermore, GABA receptors are a primary target for several neuroactive drugs including barbiturates, steroids, general anesthetics, and benzodiazepines (BZ); the latter of which is the subject of this proposal. Although it has been known for quite some time that BZs modulate GABA receptors, the molecular mechanism is still unresolved. This proposal will use a combination of molecular biology, electrophysiology, single oocyte radioactive ligand binding, and site directed fluorescent labeling to gain structural and functional insights into the actions of BZs on GABA receptors. Some of these techniques are new to the BZ field and it is hoped they will bring some fresh perspectives to the problem. The design of more efficacious BZs that can target the many different GABA receptor subtypes that have been identified in the brain will ultimately depend on understanding the structural requirements and precise mechanism of action of this important class of neuroactive compounds. The results from these proposed studies are expected to contribute to that effort. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MECHANISMS MODULATION
OF
INHIBITORY
GLYCINE
RECEPTOR
Principal Investigator & Institution: Thio, Kwee L.; Neurology; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2007 Summary: K. Liu Lin Thio, MD, PhD is a pediatric epileptologist who is interested in developing a research career in ion channel modulation because of its importance to understanding and treating neurological diseases such as epilepsy. He has extensive experience with cellular neurophysiology but would like to probe the molecular mechanisms underlying ion channel modulation. This requires that he learn the basic techniques of molecular biology, which is one of the goals of this proposal. Several neurological disorders including epilepsy may result, in part, from cortical inhibitory glycine receptor (GlyR) dysfunction. Thus, GlyR modulation is important to understanding and treating neurological disease. Although several modulators of GlyR have been identified, their mechanisms of action are unknown because quantitative pharmacological and electrophysiological studies have not been performed. This study proposes to test three hypotheses regarding the mechanism by which three known GlyR modulators act: 1) GlyR and gamma-aminobutyric acidA (GABAA) receptors interact through the cytoskeleton; 2) Sulfhydryl reducing agents inhibit GlyR by chelating extracellular zinc; 3) Potentiation and inhibition of GlyR currents by barbiturates occur at distinct sites. These hypotheses will be tested by studying the electrophysiological properties of native GlyR in cultured embryonic mouse hippocampal neurons and GlyR expressed at Xenopus oocytes and human embryonic kidney (HEK) 293 cells.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEURAL ACTIONS OF TOLUENE Principal Investigator & Institution: Woodward, John J.; Professor; Physiology and Neuroscience; Medical University of South Carolina 171 Ashley Ave Charleston, Sc 29425 Timing: Fiscal Year 2002; Project Start 15-APR-2002; Project End 28-FEB-2007 Summary: (provided by applicant): Volatile solvents such as toluene, benzene and trichloroethane are widely distributed in a variety of products encountered in both industrial and home settings. These include glues, thinners, rubber cements, aerosol sprays, nail polish removers, correction fluid and dry cleaning solvents. Although the occupational hazards of exposure to these solvents have been previously examined in a variety of toxicological studies, the cellular and molecular sites of action that account for their intoxicating effects are virtually unknown. Surveys of drug use show that a significant percentage of the population has used volatile solvents for their intoxicating properties and such use is especially prevalent among adolescents and teens who may have easy access to these products. Previous behavioral studies show that toluene and other abused volatile solvents display actions similar to that observed for CNS depressants such as ethanol, barbiturates, benzodiazepines, and anesthetics. Thus, we hypothesize that abused solvents, like other CNS depressants, may exert some of its neurobehavioral effects by altering the function of specific ion channels that are involved in mediating and modulating neuronal transmission. We have generated data to support this hypothesis and have demonstrated that toluene and other volatile solvents inhibit the function of recombinant and native NMDA and acetylcholine receptors expressed in oocytes and cultured neurons. This inhibition was dosedependent and was influenced by the subunit composition expressed. In contrast to ethanol, toluene had negligible effects on currents mediated by non-NMDA receptors or on G-protein coupled potassium channels. These results suggest that abused solvents may show greater selectivity than alcohol with respect to their ability to modulate the activity of neuronal ion channels. Studies outlined in this proposal will test this hypothesis by determining the sensitivity of recombinant and native ion channels to toluene and other volatile solvents that are subject to abuse. Two-electrode voltageclamp and patch-clamp electrophysiology will be used to analyze the solvent sensitivity of recombinant ionotropic receptors expressed in oocytes and HEK cells. The molecular sites of action for toluene will be explored by testing whether sites known to regulate the alcohol/anesthetic sensitivity of these channels also regulate solvent sensitivity. Finally, the relevance of the findings obtained in recombinant receptor systems will be assessed by measuring the effects of toluene and other abused solvents on ion channels expressed in cultured brain neurons using whole-cell patch clamp and calcium imaging. Results obtained from these studies outlined are expected to greatly expand our knowledge of the cellular and molecular targets of these important drugs of abuse. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: RECOMBINANT/NATIVE GABAA RECEPTORS Principal Investigator & Institution: Macdonald, Robert L.; Professor; Neurology; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 01-MAY-1995; Project End 30-APR-2004 Summary: (from applicant's abstract) GABA is the major inhibitory neurotransmitter in the brain. Fast inhibitory post-synaptic potentials are mediated by GABAA receptors
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(GABARs), which contain binding sites for many clinically relevant drugs such as benzodiazepines, barbiturates, and general anesthetics. GABAR currents are also modulated by neurosteroids and lanthanum and antagonized by penicillin, picrotoxin, bicuculline, furosemide, and zinc. The GABAR is a hetero-oligomeric protein complex composed of five subunits which together form a transmembrane chloride ion channel. Four different subunit families (alpha, beta, gamma, delta) have been studied extensively and two new subunit families pi and epsilon have been identified recently. Each subunit family is composed of one or more subtypes. Six alpha (alpha1-alpha6), three beta (beta1-beta3), three gamma(gamma1-gamma3), and delta(delta1), one e (e1) and one pi(pi1) subunit subtypes have been identified. Pharmacological studies of recombinant receptors have shown that individual subtypes confer different sensitivities to GABAR modulators such as benzodiazepines, barbiturates, propofol, loreclezole, alcohol, furosemide, zinc, other divalent cations and lanthanum. The hypotheses to be tested are the following: 1) GABAR subunit subtypes contain binding and modulatory sites that are subtype specific. 2) Allosteric modulators bind to N-terminal, extracellular portions of M2 or M2-M2 extracellular domains. 3) Binding of allosteric modulators bind to a restricted number of amino acid residues on these extracellular domains. 4) The kinetic properties of GABARs, including gating and desensitization, are subunit subtype specific. 5) Specific functional domains are present in the transmembrane portion of GABAR subunit subtypes that determine their kinetic properties. The specific aims are to determine: 1) Binding site(s) on GABAR beta and/or alpha subtypes for zinc and other divalent cations. 2) Modulatory sites on alpha, gamma, delta, and epsilon subtypes that regulate sensitivity to zinc and other divalent cations. 3) Binding sites on GABAR subtypes for lanthanum enhancement and inhibitions of GABAR current. 4) Binding sites on GABAR subtypes for furosemide inhibition of GABAR current. 5) Binding sites on GABAR subtypes for barbiturate enhancement of GABAR current and direct activation of current. 6) Biophysical properties of recombinant GABAR isoforms assembled from GABAR subtypes that are expressed in hippocampal dentate granule cells. 7) Structural bases for the biophysical properties of recombinant GABAR isoforms that are assembled from GABAR subtypes expressed in hippocampal dentate granule cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF NEURONAL RECEPTORS Principal Investigator & Institution: Barnes, Eugene M.; Professor of Biochemistry; Biochem and Molecular Biology; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-AUG-1991; Project End 30-APR-2003 Summary: GABAA receptors (GABAARs) are the major sites for fast synaptic inhibition in the brain. The long-term goal of this project is to understand the neuronal regulation of GABAAR density and subcellular distribution. The investigators have previously demonstrated that acute exposure of cortical neurons to GABA or benzodiazepine agonists induces the transfer of surface GABAARs into a labile intracellular pool. In order to examine the underlying mechanisms and to evaluate their role in agonistevoked GABAAR downregulation, three specific objectives are developed in this proposal. (1) To test the hypothesis that acute exposure of cortical neurons to benzodiazepines induces the sequestration of GABAAR subunits. Exoplasmic regions of GABAAR polypeptides on living neurons will be labeled with impermeant cleavable reagents. Following acute exposure to agonists, sequestered receptors will be recovered by stripping the surface label and doubly immunoprecipitating cell extracts with
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antibodies against GABAAR alpha1, beta2, and beta4 subunits. (2) To test the hypothesis that interactions of GABAARs with coated-pit proteins are evoked by agonists. The agonist-induced interactions of GABAAR subunits with inositol polyphosphate binding proteins as well as proteins identified by yeast two-hybrid screening will be examined by co-precipitation. (3) To test the hypothesis that GABAARs are degraded by distinct agonist-dependent and agonist-independent pathways. GABAAR subunits will be labeled internally by incorporation of 35S-Met/Cys and externally by impermeant noncleavable reagents. The effect of agonists and protease inhibitors on the turnover rates will be determined. It is suggested that this project will provide new insights into pathways which modulate synaptic function. By means of these regulatory mechanisms, cell-cell communication and drug-cell interaction can produce persistent changes in neuronal excitability. Furthermore, these are likely to represent molecular mechanisms which establish tolerance and habituation to benzodiazepines, barbiturates, and alcohol. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SELF-ADMINISTRATION OF ABUSED INHALANTS IN MICE Principal Investigator & Institution: Bowen, Scott E.; Psychology; Wayne State University 656 W. Kirby Detroit, Mi 48202 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2005 Summary: (provided by applicant): Although the abuse of inhalants continues to be a significant public health problem throughout the U.S. and the world, there has been very little systematic examination of the reinforcing properties of these compounds. Therefore, the aim of this research proposal is to investigate and develop a method of inhalant self-administration that can be used long-term in mice to simulate the full array of human behaviors associated with solvent abuse including acquisition, maintenance, extinction and reinstatement of both inhalant-seeking and inhalant-taking behavior. This research will focus on the current hypothesis that a majority of the abused inhalants produce a profile of neurobehavioral effects that are analogous to those produced by abused depressant drugs (e.g. barbiturates, alcohol, benzodiazepines) [Evans and Balster, 1991]. A key objective of this research proposal is the design and implementation of a preclinical model of inhalant self-administration with a primary focus on the abused inhalants toluene and 1,1,1-trichloroethane. We are proposing two series of studies for this grant. In the first series, we propose to characterize the subjective and psychomotor effects of toluene and 1,1,1-trichloroethane and to compare them to other abused inhalants. The information collected from the first series of tests will then be used as a guide for our next series of studies. In the second series of studies, we propose to design and build an apparatus (i.e., a dynamic solvent delivery system interfaced with an operant monitoring system), which will reliably deliver a "dose" of inhalant on an intermittent basis. Once completed, we will use the system to develop and validate this method of solvent inhalation by training mice to press a lever for inhalant delivery and by varying both the "dose" of inhalant and the response requirements necessary for obtaining it. Finally, the research described in the present application will extend the knowledge base of psychomotor and subjective effects of abused inhalants. In addition, this research will have important implications for understanding basic mechanisms underlying and controlling inhalant abuse, for the development of treatment medications and behavioral techniques for modifying the abuse of inhalants. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: STRUCTURE OF THE GABA A RECEPTOR BINDING SITES Principal Investigator & Institution: Czajkowski, Cynthia M.; Associate Professor; Physiology; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2004; Project Start 01-DEC-1996; Project End 30-NOV-2007 Summary: (provided by applicant): Gamma-aminobutyric acid type A receptors (GABAARs) mediate the majority of synaptic inhibition in the brain and the actions of drugs such as benzodiazepines, barbiturates and anesthetics. Recently, mutations in the receptor have been linked to epilepsy. The long-term goal of our research program is to understand the function of the GABAAR in terms of its molecular structure. Work during the current project period significantly advanced our understanding of the structure of the GABA and benzodiazepine (BZD) binding sites. Experiments proposed herein build on this information to advance our understanding, on a structural level, of how GABA binding triggers channel activation and how BZD binding is coupled to receptor modulation. We propose to 1) identify local movements within the GABA binding site that couple binding to gating, 2) identify residues in the juxta-pore region that couple movements in the binding site to movements in the transmembrane domains and 3) identify residues that directly couple the GABA and BZD binding sites. The approach combines site-directed mutagenesis, disulfide crosslinking, mutant cycle analysis, substituted cysteine accessibility method, patch-clamping and kinetic analysis. The successful completion of these aims will not only increase our understanding of how GABAARs function in health and disease states but will also establish testable hypotheses for elucidating how other related ligand-gated ion channels function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “barbiturates” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for barbiturates in the PubMed Central database: •
New guidelines for barbiturate-containing analgesics: Don't start, and help stop! by McLean W.; 2000 Aug 22; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=80376
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Thiobarbiturate-reacting Materials in Microorganisms. by Vincent WF, Cameron JA.; 1967 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=314983
3 4
Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.
With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.
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The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with barbiturates, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “barbiturates” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for barbiturates (hyperlinks lead to article summaries): •
A barbiturate screening assay for the Abbott AxSYM analyzer. Author(s): Adamczyk M, Douglas J, Grote J, Harrington CA. Source: Journal of Analytical Toxicology. 1998 March-April; 22(2): 105-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9547406&dopt=Abstract
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A rapid cost-effective high-performance liquid chromatographic (HPLC) assay of serum lamotrigine after liquid-liquid extraction and using HPLC conditions routinely used for analysis of barbiturates. Author(s): Hart AP, Mazarr-Proo S, Blackwell W, Dasgupta A. Source: Therapeutic Drug Monitoring. 1997 August; 19(4): 431-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9263385&dopt=Abstract
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A single amino acid confers barbiturate sensitivity upon the GABA rho 1 receptor. Author(s): Belelli D, Pau D, Cabras G, Peters JA, Lambert JJ. Source: British Journal of Pharmacology. 1999 June; 127(3): 601-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10401548&dopt=Abstract
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A single hydrophobic residue confers barbiturate sensitivity to gamma-aminobutyric acid type C receptor. Author(s): Amin J. Source: Molecular Pharmacology. 1999 March; 55(3): 411-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10051524&dopt=Abstract
6 PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.
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Automated preparation and analysis of barbiturates in human urine using the combined system of PrepStation and gas chromatography-mass spectrometry. Author(s): Namera A, Yashiki M, Okada K, Iwasaki Y, Ohtani M, Kojima T. Source: J Chromatogr B Biomed Sci Appl. 1998 March 20; 706(2): 253-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9551811&dopt=Abstract
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Automated procedure for determination of barbiturates in serum using the combined system of PrepStation and gas chromatography-mass spectrometry. Author(s): Namera A, Yashiki M, Iwasaki Y, Ohtani M, Kojima T. Source: J Chromatogr B Biomed Sci Appl. 1998 September 25; 716(1-2): 171-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9824230&dopt=Abstract
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Barbiturate anesthesia and brain proton spectroscopy. Author(s): Lundbom NM, Manner T, Komu M, Peltola O, Leino KA, Kirvela OA. Source: Ajnr. American Journal of Neuroradiology. 1999 September; 20(8): 1543-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10512243&dopt=Abstract
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Barbiturate anticonvulsants: a neuropsychological and quantitative electroencephalographic study. Author(s): Willis J, Nelson A, Black FW, Borges A, An A, Rice J. Source: Journal of Child Neurology. 1997 April; 12(3): 169-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9130089&dopt=Abstract
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Barbiturate coma for intracranial hypertension: clinical observations. Author(s): Dereeper E, Berre J, Vandesteene A, Lefranc F, Vincent JL. Source: Journal of Critical Care. 2002 March; 17(1): 58-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12040550&dopt=Abstract
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Barbiturate coma in severe hemispheric stroke: useful or obsolete? Author(s): Schwab S, Spranger M, Schwarz S, Hacke W. Source: Neurology. 1997 June; 48(6): 1608-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9191775&dopt=Abstract
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Barbiturate coma may promote reversible bone marrow suppression in patients with severe isolated traumatic brain injury. Author(s): Stover JF, Stocker R. Source: European Journal of Clinical Pharmacology. 1998 September; 54(7): 529-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9832294&dopt=Abstract
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Barbiturates and lung cancer: a re-evaluation. Author(s): Friedman GD, Habel LA. Source: International Journal of Epidemiology. 1999 June; 28(3): 375-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10405836&dopt=Abstract
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Barbiturates and the brain. Author(s): Pearce RA. Source: Anesthesiology. 1999 November; 91(5): 1190-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10551566&dopt=Abstract
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Barbiturates for acute traumatic brain injury. Author(s): Roberts I. Source: Cochrane Database Syst Rev. 2000; (2): Cd000033. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10796689&dopt=Abstract
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Barbiturates in the treatment of epilepsy in people with intellectual disability. Author(s): Alvarez N. Source: Journal of Intellectual Disability Research : Jidr. 1998 December; 42 Suppl 1: 1623. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10030427&dopt=Abstract
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Barbiturates inhibit progesterone synthesis in cultured Leydig tumor cells and human granulosa cells. Author(s): Gocze PM, Szabo I, Porpaczy Z, Freeman DA. Source: Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology. 1999 October; 13(5): 305-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10599546&dopt=Abstract
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Barbiturates, smoking, and bladder cancer risk. Author(s): Habel LA, Bull SA, Friedman GD. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 1998 November; 7(11): 1049-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9829715&dopt=Abstract
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Barbiturates. Author(s): Coupey SM. Source: Pediatrics in Review / American Academy of Pediatrics. 1997 August; 18(8): 260-4; Quiz 265. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9255991&dopt=Abstract
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Biological determinants of P300: the effects of a barbiturate on latency and amplitude. Author(s): Fowler B, Mitchell I. Source: Biological Psychology. 1997 August 22; 46(2): 113-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9288409&dopt=Abstract
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Cerebral hypoperfusion after cardiac surgery and anesthetic strategies: a comparative study with high dose fentanyl and barbiturate anesthesia. Author(s): Gunaydin B, Babacan A. Source: Ann Thorac Cardiovasc Surg. 1998 February; 4(1): 12-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9501262&dopt=Abstract
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Comparative effects of hypothermia, barbiturate, and osmotherapy for cerebral oxygen metabolism, intracranial pressure, and cerebral perfusion pressure in patients with severe head injury. Author(s): Nara I, Shiogai T, Hara M, Saito I. Source: Acta Neurochir Suppl (Wien). 1998; 71: 22-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9779133&dopt=Abstract
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Comparison of the serum barbiturate fluorescence polarization immunoassay by the COBAS INTEGRA to a GC/MS method. Author(s): Cannon RD, Wong SH, Gock SB, Jentzen JJ. Source: Therapeutic Drug Monitoring. 1999 October; 21(5): 553-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10519455&dopt=Abstract
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Depth of EEG suppression and outcome in barbiturate anesthetic treatment for refractory status epilepticus. Author(s): Krishnamurthy KB, Drislane FW. Source: Epilepsia. 1999 June; 40(6): 759-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10368075&dopt=Abstract
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Determination in serum of some barbiturates using micellar liquid chromatography with direct injection. Author(s): Elisa Capella-Peiro M, Gil-Agusti M, Martinavarro-Dominguez A, EsteveRomero J. Source: Analytical Biochemistry. 2002 October 15; 309(2): 261-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12413460&dopt=Abstract
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Determination of barbiturates in urine by micellar liquid chromatography and direct injection of sample. Author(s): Martin-Biosca Y, Sagrado S, Villaneuva-Camanas RM, Medina-Hernandez MJ. Source: Journal of Pharmaceutical and Biomedical Analysis. 1999 November; 21(2): 3318. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10703988&dopt=Abstract
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Does barbiturate therapy cause severe hypokalemia? Author(s): Irita K, Kawasaki T, Uenotsuchi T, Sakaguchi Y, Takahashi S. Source: Anesthesia and Analgesia. 1998 January; 86(1): 214. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9428881&dopt=Abstract
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Effect of barbiturate on central pain: difference between intravenous administration and oral administration. Author(s): Koyama T, Arakawa Y, Shibata M, Mashimo T, Yoshiya I. Source: The Clinical Journal of Pain. 1998 March; 14(1): 86-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9535318&dopt=Abstract
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Effect of barbiturates on hydroxyl radicals, lipid peroxidation, and hypoxic cell death in human NT2-N neurons. Author(s): Almaas R, Saugstad OD, Pleasure D, Rootwelt T. Source: Anesthesiology. 2000 March; 92(3): 764-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10719955&dopt=Abstract
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Effect of some psychotropic drugs and a barbiturate on mycoplasmas. Author(s): Lind K, Kristiansen JE. Source: International Journal of Antimicrobial Agents. 2000 April; 14(3): 235-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10773494&dopt=Abstract
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Effects of barbiturates on facilitative glucose transporters are pharmacologically specific and isoform selective. Author(s): Haspel HC, Stephenson KN, Davies-Hill T, El-Barbary A, Lobo JF, Croxen RL, Mougrabi W, Koehler-Stec EM, Fenstermacher JD, Simpson IA. Source: The Journal of Membrane Biology. 1999 May 1; 169(1): 45-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10227851&dopt=Abstract
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Effects of combining midazolam and barbiturate on the response to tracheal intubation: changes in autonomic nervous system. Author(s): Nishiyama T, Misawa K, Yokoyama T, Hanaoka K. Source: Journal of Clinical Anesthesia. 2002 August; 14(5): 344-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12208438&dopt=Abstract
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Efficacy of five days' barbiturate anesthesia in the treatment of intractable epilepsies in children. Author(s): Rantala H, Saukkonen AL, Remes M, Uhari M. Source: Epilepsia. 1999 December; 40(12): 1775-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10612343&dopt=Abstract
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Emergency! Barbiturate overdose. Author(s): Lisanti P. Source: The American Journal of Nursing. 1998 October; 98(10): 38. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9803217&dopt=Abstract
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Evaluation of Emit tox benzodiazepine and barbiturate assays on the Vitalab Viva analyser and FPIA on the Abbott ADx analyser. Author(s): Charlier CJ, Plomteux GJ. Source: Clinical Chemistry and Laboratory Medicine : Cclm / Fescc. 2000 July; 38(7): 615-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11028766&dopt=Abstract
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Extensive subdural empyema treated with drainage and barbiturate therapy under intracranial pressure monitoring: case report. Author(s): Kageyama G, Park KC, Yoshimine Y, Yokota J. Source: Neurological Research. 2000 September; 22(6): 601-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11045023&dopt=Abstract
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Forced diuresis after barbiturates. Author(s): Ohlsson WT. Source: Lancet. 1967 October 21; 2(7521): 888. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12389552&dopt=Abstract
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GC/MS confirmation of barbiturates in blood and urine. Author(s): Meatherall R. Source: J Forensic Sci. 1997 November; 42(6): 1160-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9397563&dopt=Abstract
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GLUT1-deficiency: barbiturates potentiate haploinsufficiency in vitro. Author(s): Klepper J, Fischbarg J, Vera JC, Wang D, De Vivo DC. Source: Pediatric Research. 1999 December; 46(6): 677-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10590023&dopt=Abstract
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Granulocyte colony-stimulating factor ameliorates life-threatening infections after combined therapy with barbiturates and mild hypothermia in patients with severe head injuries. Author(s): Ishikawa K, Tanaka H, Takaoka M, Ogura H, Shiozaki T, Hosotsubo H, Shimazu T, Yoshioka T, Sugimoto H. Source: The Journal of Trauma. 1999 June; 46(6): 999-1007; Discussion 1007-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10372615&dopt=Abstract
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Guidelines for the acute medical management of severe traumatic brain injury in infants, children, and adolescents. Chapter 13. The use of barbiturates in the control of intracranial hypertension in severe pediatric traumatic brain injury. Author(s): Adelson PD, Bratton SL, Carney NA, Chesnut RM, du Coudray HE, Goldstein B, Kochanek PM, Miller HC, Partington MD, Selden NR, Warden CR, Wright DW; American Association for Surgery of Trauma; Child Neurology Society; International Society for Pediatric Neurosurgery; International Trauma Anesthesia and Critical Care Society; Society of Critical Care Medicine; World Federation of Pediatric Intensive and Critical Care Societies. Source: Pediatric Critical Care Medicine : a Journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies. 2003 July; 4(3 Suppl): S49-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12847349&dopt=Abstract
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Hypertonic saline solution for control of elevated intracranial pressure in patients with exhausted response to mannitol and barbiturates. Author(s): Horn P, Munch E, Vajkoczy P, Herrmann P, Quintel M, Schilling L, Schmiedek P, Schurer L. Source: Neurological Research. 1999 December; 21(8): 758-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10596385&dopt=Abstract
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In vitro reaction of barbiturates with formaldehyde. Author(s): Gannett PM, Daft JR, James D, Rybeck B, Knopp JB, Tracy TS. Source: Journal of Analytical Toxicology. 2001 September; 25(6): 443-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11550818&dopt=Abstract
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Inhibition of glucose transport and direct interactions with type 1 facilitative glucose transporter (GLUT-1) by etomidate, ketamine, and propofol: a comparison with barbiturates. Author(s): Stephenson KN, Croxen RL, El-Barbary A, Fenstermacher JD, Haspel HC. Source: Biochemical Pharmacology. 2000 September 1; 60(5): 651-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10927023&dopt=Abstract
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Is there an indication for the use of barbiturate-containing analgesic agents in the treatment of pain? Guidelines for their safe use and withdrawal management. Canadian Pharmacists Association. Author(s): McLean W, Boucher EA, Brennan M, Holbrook A, Orser R, Peachey J, Sellers E. Source: Can J Clin Pharmacol. 2000 Winter; 7(4): 191-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11118965&dopt=Abstract
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Life-threatening hyperkalaemia following therapeutic barbiturate coma. Author(s): Cairns CJ, Thomas B, Fletcher S, Parr MJ, Finfer SR. Source: Intensive Care Medicine. 2002 September; 28(9): 1357-60. Epub 2002 July 18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12209290&dopt=Abstract
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Mutation of the GABAA receptor M1 transmembrane proline increases GABA affinity and reduces barbiturate enhancement. Author(s): Greenfield LJ Jr, Zaman SH, Sutherland ML, Lummis SC, Niemeyer MI, Barnard EA, Macdonald RL. Source: Neuropharmacology. 2002 March; 42(4): 502-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11955521&dopt=Abstract
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New fluorescence polarization immunoassays for analysis of barbiturates and benzodiazepines in serum and urine: performance characteristics. Author(s): Schwenzer KS, Pearlman R, Tsilimidos M, Salamone SJ, Cannon RC, Wong SH, Gock SB, Jentzen JJ. Source: Journal of Analytical Toxicology. 2000 November-December; 24(8): 726-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11110029&dopt=Abstract
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New guidelines for barbiturate-containing analgesics: don't start, and help stop! Author(s): McLean W. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2000 August 22; 163(4): 414-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10976258&dopt=Abstract
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Positive screening tests for barbiturates in urine samples in the York area over a 1year period. Author(s): Holbrook I, Sinclair M, Turley P, Tetlow T. Source: Annals of Clinical Biochemistry. 2001 September; 38(Pt 5): 559-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11587136&dopt=Abstract
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Pro: arguments for use of barbiturates in infants and children undergoing deep hypothermic circulatory arrest. Author(s): Reid RW, Warner DS. Source: Journal of Cardiothoracic and Vascular Anesthesia. 1998 October; 12(5): 591-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9801985&dopt=Abstract
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Profound increase in epinephrine concentration in plasma and cardiovascular stimulation after mu-opioid receptor blockade in opioid-addicted patients during barbiturate-induced anesthesia for acute detoxification. Author(s): Kienbaum P, Thurauf N, Michel MC, Scherbaum N, Gastpar M, Peters J. Source: Anesthesiology. 1998 May; 88(5): 1154-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9605673&dopt=Abstract
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Recombinant human 5-HT3A receptors in outside-out patches of HEK 293 cells: basic properties and barbiturate effects. Author(s): Barann M, Meder W, Dorner Z, Bruss M, Bonisch H, Gothert M, Urban BW. Source: Naunyn-Schmiedeberg's Archives of Pharmacology. 2000 September; 362(3): 255-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10997728&dopt=Abstract
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Risk of drug dependence and abuse posed by barbiturate-containing analgesics. Author(s): Sellers EM, Hoornweg K, Busto UE, Romach MK. Source: Can J Clin Pharmacol. 1999 Spring; 6(1): 18-25. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10465862&dopt=Abstract
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Screening for drugs of abuse (II): Cannabinoids, lysergic acid diethylamide, buprenorphine, methadone, barbiturates, benzodiazepines and other drugs. Author(s): Simpson D, Braithwaite RA, Jarvie DR, Stewart MJ, Walker S, Watson IW, Widdop B. Source: Annals of Clinical Biochemistry. 1997 September; 34 ( Pt 5): 460-510. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9293303&dopt=Abstract
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Shoulder-hand syndrome in neurosurgical patients treated with barbiturates. A long term evaluation. Author(s): De Santis A, Ceccarelli G, Cesana BM, Bello L, Spagnoli D, Villani RM. Source: Journal of Neurosurgical Sciences. 2000 June; 44(2): 69-75; Discussion 75-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11105834&dopt=Abstract
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Suicide by injection of a veterinarian barbiturate euthanasia agent: report of a case and toxicological analysis. Author(s): Romain N, Giroud C, Michaud K, Mangin P. Source: Forensic Science International. 2003 January 28; 131(2-3): 103-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12590047&dopt=Abstract
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The 1.8-A crystal structure of a matrix metalloproteinase 8-barbiturate inhibitor complex reveals a previously unobserved mechanism for collagenase substrate recognition. Author(s): Brandstetter H, Grams F, Glitz D, Lang A, Huber R, Bode W, Krell HW, Engh RA. Source: The Journal of Biological Chemistry. 2001 May 18; 276(20): 17405-12. Epub 2001 January 22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11278347&dopt=Abstract
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The history of intravenous anaesthesia: the barbiturates. Part 1. Author(s): Ball C, Westhorpe R. Source: Anaesthesia and Intensive Care. 2001 April; 29(2): 97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11314844&dopt=Abstract
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The history of intravenous anaesthesia: the barbiturates. Part 2. Author(s): Ball C, Westhorpe R. Source: Anaesthesia and Intensive Care. 2001 June; 29(3): 219. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11439791&dopt=Abstract
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The history of intravenous anaesthesia: the barbiturates. Part 3. Author(s): Ball C, Westhorpe R. Source: Anaesthesia and Intensive Care. 2001 August; 29(4): 323. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11512641&dopt=Abstract
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Theoretical modeling of oral absorption of barbiturates. Author(s): Ghafourian T, Barzegar-Jalali M. Source: Farmaco (Societa Chimica Italiana : 1989). 2002 July; 57(7): 565-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12164215&dopt=Abstract
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Thiobarbiturates interfere with the Dade Behring aca ammonia test. Author(s): Cochrane Database Syst Rev. 2001;(2):CD000164 Source: Clinical Chemistry. 2000 May; 46(5): 735-6. /entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11405952
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Transient diffuse cerebral hypoperfusion in Tc-99m HMPAO SPECT of the brain during withdrawal syndrome following acute barbiturate poisoning. Author(s): Kamijo Y, Soma K, Kondo R, Ohwada T. Source: Vet Hum Toxicol. 2002 December; 44(6): 348-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12458639&dopt=Abstract
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Transmembrane water influx via aquaporin-1 is inhibited by barbiturates and propofol in red blood cells. Author(s): Voigtlaender J, Heindl B, Becker BF. Source: Naunyn-Schmiedeberg's Archives of Pharmacology. 2002 September; 366(3): 209-17. Epub 2002 July 03. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12172703&dopt=Abstract
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Use of barbiturates in the treatment of cyclic vomiting during childhood. Author(s): Gokhale R, Huttenlocher PR, Brady L, Kirschner BS. Source: Journal of Pediatric Gastroenterology and Nutrition. 1997 July; 25(1): 64-7. Erratum In: J Pediatr Gastroenterol Nutr 1997 November; 25(5): 559. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9226529&dopt=Abstract
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CHAPTER 2. NUTRITION AND BARBITURATES Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and barbiturates.
Finding Nutrition Studies on Barbiturates The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail:
[email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “barbiturates” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.
7 Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.
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The following information is typical of that found when using the “Full IBIDS Database” to search for “barbiturates” (or a synonym): •
Barbiturates induce mitochondrial depolarization and potentiate excitotoxic neuronal death. Author(s): Department of Neurology, University of California, San Francisco, USA. Source: Anderson, C M Norquist, B A Vesce, S Nicholls, D G Soine, W H Duan, S Swanson, R A J-Neurosci. 2002 November 1; 22(21): 9203-9 1529-2401
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Barbiturates inhibit stress-induced analgesia. Source: Kissin, I Mason, J O 3rd Vinik, H R McDanal, J Bradley, E L Can-J-Anaesth. 1987 March; 34(2): 146-51 0832-610X
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Benzodiazepines and barbiturate potentiate the pre- and postsynaptic gammaaminobutyric acid (GABA)A receptor-mediated response in the enteric nervous system of guinea pig small intestine. Author(s): Department of Pharmacology, Kobe University School of Medicine, Japan. Source: Taniyama, K Hashimoto, S Hanada, S Tanaka, C J-Pharmacol-Exp-Ther. 1988 April; 245(1): 250-6 0022-3565
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Blockade of glutamate receptors and barbiturate anesthesia: increased sensitivity to pentobarbital-induced anesthesia despite reduced inhibition of AMPA receptors in GluR2 null mutant mice. Author(s): Department of Anaesthesia, University of Toronto, Ontario, Canada. Source: Joo, D T Xiong, Z MacDonald, J F Jia, Z Roder, J Sonner, J Orser, B A Anesthesiology. 1999 November; 91(5): 1329-41 0003-3022
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Comparison of the effects of convulsant and depressant barbiturate stereoisomers on AMPA-type glutamate receptors. Author(s): Department of Anesthesiology, Yokohama City University School of Medicine, Japan. Source: Kamiya, Y Andoh, T Furuya, R Hattori, S Watanabe, I Sasaki, T Ito, H Okumura, F Anesthesiology. 1999 June; 90(6): 1704-13 0003-3022
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Depressant and convulsant barbiturates both inhibit neuronal nicotinic acetylcholine receptors. Author(s): Department of Anesthesiology, Yokohama City University School of Medicine, Yokohama, Japan. Source: Watanabe, I Andoh, T Furuya, R Sasaki, T Kamiya, Y Itoh, H Anesth-Analg. 1999 June; 88(6): 1406-11 0003-2999
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Effects of oxybarbiturates on fern spore germination and gametophyte development. Source: Bannon, M.E. Kordan, H.A. Sheffield, E. ATLA,-Altern-lab-anim. Nottingham : Fund for the Replacement of Animals in Medical Experiments. July 1991. volume 19 (3) page 308-315. 0261-1929
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Improved maintenance of adult rat hepatocytes in a new serum-free medium in the presence or absence of barbiturates. Author(s): Division of Pathology, Okayama University Medical School, Japan. Source: Miyazaki, M Suzuki, Y Oda, M Kawai, A Bai, L Y Sato, J In-Vitro-Cell-Dev-Biol. 1989 September; 25(9): 839-48 0883-8364
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Increases in neuronal Ca2+ flux after withdrawal from chronic barbiturate treatment. Author(s): Psychology Department, Durham University, UK. Source: Rabbani, M Little, H J Eur-J-Pharmacol. 1999 January 8; 364(2-3): 221-7 0014-2999
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Mechanisms of neurotransmission of valproate sodium in suppressing barbiturate and phenytoin withdrawal syndrome. Author(s): University of Medicine, Department of Pharmacology and Medicinal Toxicology, Plovdiv, Bulgaria. Source: Peichev, L Folia-Med-(Plovdiv). 1992; 34(2): 14-9 0204-8043
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Modulation of the developing rat sympathetic GABAA receptor by Zn++, benzodiazepines, barbiturates and ethanol. Author(s): Laboratory of Neuropharmacology, Catholic University at Valparaiso, Chile. Source: Aguayo, L G Alarcon, J M J-Pharmacol-Exp-Ther. 1993 December; 267(3): 141422 0022-3565
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Production of hydrogen peroxide by alveolar macrophages. Effect of barbiturates. Author(s): Department of Medical Chemistry and Biochemistry, Second Faculty of Medicine, Charles University, Prague, Czech Republic. Source: Wilhelm, J Sojkova, J Herget, J Physiol-Res. 1995; 44(6): 369-75 0862-8408
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Promotion of liver carcinogenesis: interactions of barbiturates and a choline-deficient diet. Source: Shinozuka, H. Demetris, A.J. Katyal, S.L. Perera, M.I.R. A-C-S-Symp-Ser-AmChem-Soc. Washington, D.C. : The Society. 1985. (277) page 327-336. 0097-6156
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Study of the participation of the dopaminergic transmission system in the effects of two newly synthesized barbiturates. Author(s): Experimental Pharmacology Department, Bulgarian Academy of Sciences. Source: Getova, D Markovska, V Acta-Physiol-Pharmacol-Bulg. 1988; 14(2): 56-62 03239950
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Suppression of experimental barbiturate and phenytoin withdrawal syndrome using valproate sodium. Author(s): Department of Pharmacology and Drug Toxicology, University of Medicine, Plovdiv, Bulgaria. Source: Peichev, L Folia-Med-(Plovdiv). 1992; 34(3-4): 3-7 0204-8043
Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •
healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0
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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov
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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov
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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/
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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/
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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/
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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/
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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/
Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html
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Google: http://directory.google.com/Top/Health/Nutrition/
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Healthnotes: http://www.healthnotes.com/
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Open Directory Project: http://dmoz.org/Health/Nutrition/
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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/
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WebMD®Health: http://my.webmd.com/nutrition
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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CHAPTER 3. ALTERNATIVE MEDICINE AND BARBITURATES Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to barbiturates. 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 barbiturates 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 “barbiturates” (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 barbiturates: •
“Hotness” stability of chicken hot-wing products as affected by preparation methods and storage. Author(s): Chang MH, Chen TC. Source: Poultry Science. 1998 April; 77(4): 627-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9565248&dopt=Abstract
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“Recovered memory” therapy for eating disorders: implications of the Ramona verdict. Author(s): Pope HG Jr, Hudson JI. Source: The International Journal of Eating Disorders. 1996 March; 19(2): 139-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8932552&dopt=Abstract
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3,4,5-Trihydroxy benzoic acid (gallic acid), the hepatoprotective principle in the fruits of Terminalia belerica-bioassay guided activity. Author(s): Anand KK, Singh B, Saxena AK, Chandan BK, Gupta VN, Bhardwaj V.
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Source: Pharmacological Research : the Official Journal of the Italian Pharmacological Society. 1997 October; 36(4): 315-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9425622&dopt=Abstract •
3,5-Dichloroaniline toxicity in Fischer 344 rats pretreated with inhibitors and inducers of cytochrome P450. Author(s): Valentovic MA, Lo HH, Brown PI, Rankin GO. Source: Toxicology Letters. 1995 August; 78(3): 207-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7624891&dopt=Abstract
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Barbiturate induced benzophenanthridine alkaloid formation proceeds by gene transcript accumulation in the California poppy. Author(s): Haider G, Kislinger T, Kutchan TM. Source: Biochemical and Biophysical Research Communications. 1997 December 18; 241(2): 606-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9425319&dopt=Abstract
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Effects of atipamezole, an alpha 2-adrenoceptor antagonist, on the anesthesia induced by barbiturates and medetomidine. Author(s): Kauppila T, Jyvasjarvi E, Pertovaara A. Source: Anesthesia and Analgesia. 1992 September; 75(3): 416-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1354946&dopt=Abstract
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Electrophysiology of ethanol, nitrous oxide, and barbiturate on presumed subtypes of cerebellar granule cells. Author(s): Huang C, Liu G, Hsiao CF, Huang R. Source: Annals of the New York Academy of Sciences. 1991; 625: 264-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2058885&dopt=Abstract
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Inferior colliculus unitary activity in wakefulness, sleep and under barbiturates. Author(s): Torterolo P, Falconi A, Morales-Cobas G, Velluti RA. Source: Brain Research. 2002 May 10; 935(1-2): 9-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12062467&dopt=Abstract
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Normative N1 audiogram data for the barbiturate-anaesthetised domestic cat. Author(s): Rajan R, Irvine DR, Cassell JF. Source: Hearing Research. 1991 May; 53(1): 153-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2066283&dopt=Abstract
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Potentiating effect of 1,2,4-thiadiazolidines on barbiturate-induced hypnosis in albino mice. Author(s): Srivastava K, Siddiqui N, Pandeya SN.
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Source: Pharmazie. 1992 May; 47(5): 394-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1409838&dopt=Abstract •
Response map properties of units in the dorsal cochlear nucleus of barbiturateanesthetized gerbil (Meriones unguiculatus). Author(s): Gdowski GT, Voigt HF. Source: Hearing Research. 1997 March; 105(1-2): 85-104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9083807&dopt=Abstract
Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •
Alternative Medicine Foundation, Inc.: http://www.herbmed.org/
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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats
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Chinese Medicine: http://www.newcenturynutrition.com/
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drkoop.com®: http://www.drkoop.com/InteractiveMedicine/IndexC.html
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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm
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Google: http://directory.google.com/Top/Health/Alternative/
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Healthnotes: http://www.healthnotes.com/
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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine
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Open Directory Project: http://dmoz.org/Health/Alternative/
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HealthGate: http://www.tnp.com/
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WebMD®Health: http://my.webmd.com/drugs_and_herbs
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/
The following is a specific Web list relating to barbiturates; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •
General Overview Cutaneous Drug Reactions Source: Integrative Medicine Communications; www.drkoop.com Insomnia Source: Integrative Medicine Communications; www.drkoop.com
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Insomnia Source: Prima Communications, Inc.www.personalhealthzone.com Serum Sickness Source: Integrative Medicine Communications; www.drkoop.com Sleeplessness Source: Integrative Medicine Communications; www.drkoop.com •
Herbs and Supplements Anticonvulsants Source: Healthnotes, Inc.; www.healthnotes.com Ava Source: Integrative Medicine Communications; www.drkoop.com Barbiturates Source: Healthnotes, Inc.; www.healthnotes.com Barbiturates Source: Integrative Medicine Communications; www.drkoop.com Butalbital Source: Healthnotes, Inc.; www.healthnotes.com Dehydroepiandrosterone (DHEA) Source: Integrative Medicine Communications; www.drkoop.com DHEA Source: Integrative Medicine Communications; www.drkoop.com English Lavendar Source: Integrative Medicine Communications; www.drkoop.com French Lavendar Source: Integrative Medicine Communications; www.drkoop.com General Anesthetics Source: Healthnotes, Inc.; www.healthnotes.com Hydrastis Alternative names: Goldenseal; Hydrastis canadensis L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Kava Alternative names: Piper methysticum Source: Healthnotes, Inc.; www.healthnotes.com Kava Kava Alternative names: Ava Source: Integrative Medicine Communications; www.drkoop.com
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Lavandula Angustifolia Source: Integrative Medicine Communications; www.drkoop.com Lavender Alternative names: Lavandula angustifolia, English Lavendar, French Lavendar Source: Integrative Medicine Communications; www.drkoop.com Lepidium Sp Alternative names: Cress; Lepidium sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Mad-Dog Skullcap Alternative names: Skullcap Source: Integrative Medicine Communications; www.drkoop.com Melissa Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10043,00.html Passiflora Incarnata Alternative names: Passionflower Source: Integrative Medicine Communications; www.drkoop.com Passionflower Alternative names: Passiflora incarnata Source: Integrative Medicine Communications; www.drkoop.com Phenobarbital Source: Healthnotes, Inc.; www.healthnotes.com Piper Methysticum Alternative names: Kava Kava Source: Integrative Medicine Communications; www.drkoop.com Scutellaria Lateriflora Alternative names: Skullcap Source: Integrative Medicine Communications; www.drkoop.com Skullcap Alternative names: Mad-dog Skullcap Source: Integrative Medicine Communications; www.drkoop.com Valerian Alternative names: Valeriana officinalis Source: Healthnotes, Inc.; www.healthnotes.com Valerian Alternative names: Valeriana officinalis Source: Integrative Medicine Communications; www.drkoop.com
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Valerian Source: Prima Communications, Inc.www.personalhealthzone.com Valeriana Officinalis Alternative names: Valerian Source: Integrative Medicine Communications; www.drkoop.com Zolpidem Source: Healthnotes, Inc.; www.healthnotes.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.
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CHAPTER 4. DISSERTATIONS ON BARBITURATES Overview In this chapter, we will give you a bibliography on recent dissertations relating to barbiturates. 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 “barbiturates” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on barbiturates, we have not necessarily excluded nonmedical dissertations in this bibliography.
Dissertations on Barbiturates 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 barbiturates. 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: •
Differential Pharmacological Effects of Ethanol, Barbiturates and Opiates in the Isolated Guinea-Pig Ileum Preparation and in the Rat by Mayer, Joel M; PhD from University of Toronto (Canada), 1983 http://wwwlib.umi.com/dissertations/fullcit/NK59832
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The Influence of Thyroxine and Barbiturates on Monoamine Oxidase Activity by Quevedo, Evaristo; AdvDeg from University of Ottawa (Canada), 1970 http://wwwlib.umi.com/dissertations/fullcit/NK08584
Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.
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CHAPTER 5. PATENTS ON BARBITURATES 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.8 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 “barbiturates” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on barbiturates, we have not necessarily excluded nonmedical patents in this bibliography.
Patents on Barbiturates By performing a patent search focusing on barbiturates, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an 8Adapted
from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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example of the type of information that you can expect to obtain from a patent search on barbiturates: •
5-benzyl barbiturate derivatives Inventor(s): Cha; Sungman (Providence, RI), el Kouni; Mahmoud H. (Providence, RI), Naguib; Fardos N. M. (Providence, RI), Panzica; Raymond (Narragansett, RI) Assignee(s): Brown University Research Foundation (providence, Ri) Patent Number: 5,141,943 Date filed: April 12, 1990 Abstract: 5-benzyl barbiturate compounds for use as water-soluble uridine phosphorylase inhibitors are disclosed. These compounds are useful for reducing the toxicity and anemia induced by antiviral drugs such as AZT, as well as for potentiating anticancer drugs and combatting their host-toxicity. Excerpt(s): This invention relates to the synthesis and measurement of novel benzyl barbiturate derivatives useful as uridine phosphorylase inhibitors in cancer and viral therapies. It is known in the art that uridine phosphorylase inhibitors possess a number of clinically useful attributes. For example, uridine phosphorylase inhibitors have been proposed as means to increase the selectivity and efficacy of various uracil and uridine derivatives in cancer chemotherapy. In another application (U.S. application Ser. No. 180,525), uridine phosphorylase inhibitors have been proposed recently as rescue agents for reducing the toxicity of antiviral agents such as 3'-azido-3'deoxythymidine (AZT). To be useful, the uridine phosphorylase inhibitors should be potent, specific, and non-toxic, and readily soluble in aqueous solutions buffered within the physiological pH range. In addition, the compounds should also be easy to make and to use. In the field of cancer chemotherapy, the use of halogenated pyrimidine bases such as 5-fluorouracil (5-FUra), and halogenated pyrimidine nucleosides such as 5-fluoro-2'-deoxyuridine (5-FdUrd) as chemotherapeutic agents is well documented in the art (Heidelberger, C., in Antineoplastic and Immune Suppressive Agents Part II, A. C. Sartorelli and D. G. Jones ed.s, pp. 193-231, (Springer-Verlag, Heidelberg, 1975)). However, the halogenated pyrimidine nucleosides are rapidly degraded to their respective pyrimidine bases, reducing their effectiveness against the cancer tissue they are meant to treat. Moreover, the pyrimidine bases, like 5-fluorouracil, are generally more toxic to the host (nontumor) tissue. Web site: http://www.delphion.com/details?pn=US05141943__
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Aminophenyl esters of 5-carboxyalkyl barbituric acids Inventor(s): Focella; Antonino (Clifton, NJ), Heveran; John Edward (Fairfield, NJ), Teitel; Sidney (Clifton, NJ), Weigele; Manfred (North Caldwell, NJ) Assignee(s): Hoffmann-la Roche Inc. (nutley, Nj) Patent Number: 4,101,549 Date filed: May 26, 1976 Abstract: Aminoaryl esters and amino-lower alkyl amides of carboxy substituted barbiturates are linked via an amide linkage to carboxylated latex polymers to form reagents which are useful in a sensitive diagnostic test to detect the presence of barbiturates in body fluids.The large increase in the abuse of therapeutic agents,
Patents 43
particularly the barbiturates, by the general population as well as military personnel, has brought with it a substantial need to improve analytical techniques for the determination of such agents in biological fluids. In many instances, medical treatment centers are faced with the immediate need for determining the identity of a barbiturate taken by a patient who is unable, being in a comatose condition, or unwilling to supply such information to the treating physician. Early procedures involved the identification of barbiturates by extraction and thin-layer, gas chromatographic and spectrophotometric methods. These techniques have the disadvantages of being relatively time-consuming, laborious and lacking great sensitivity. Recently, a rapid and sensitive immunoassay procedure involving the reaction between antibodies and barbiturate antigen was described by S. Spector in U.S. Pat. No. 3,766,162 and by S. Spector and E. J. Flynn in Science, 174, 1037 (1971). This procedure, however, requires sophisticated and expensive equipment, such as scintillation counters. Therefore, it would be desirable to develop a rapid and highly sensitive assay for detecting the presence of barbiturates in biological fluids which would not require sophisticated equipment and could be easily performed on site by laboratory technicians having a minimum of training.BRIEF DESCRIPTION OF THE INVENTIONThe present invention relates to a novel class of barbiturate derivatives, namely, aminoaryl esters and aminolower alkyl amides of carboxy substituted barbiturates, which esters and amides may be covalently coupled via an amide linkage to a carboxylated latex polymer. The barbiturate thus linked to the latex polymer by means of the linking group can then be utilized as a reagent in a sensitive diagnostic assay for the presence of barbiturates in biological fluids. This assay method is dependent upon the well known binding of antigen to antibodies specific therefor, which is manifested by an insolubilization or agglutination followed by flocculation. When either the antigen or the antibody is linked to a suitable polymer such as a latex polymer, as hereinafter described, the detection of the antigen-antibody binding by means of agglutination is significantly enhanced by means of the latex so that such agglutination reaction is easily visualized by the naked eye.The general technique of utilizing latex particles as carriers for antigens or antibodies for easy visualization of the antigen-antibody reaction has been previously described in the literature, for example, U.S. Pat. No. 3,857,931.The starting materials which are used for the preparation of the latex reagents of the present invention are aminoaryl esters and amino-lower alkyl amides of carboxy substituted barbiturates. As used herein, the expression "lower alkyl" is meant to include straight and branchedchain saturated hydrocarbon radicals having from 2 to 8 carbon atoms, inclusive, such as ethyl, propyl, n-butyl, iso-butyl and the like. The term "aryl" denotes an aromatic radical derived from an unsubstituted or substituted arene and includes phenyl, naphthyl, halophenyl, tolyl, anisyl, nitrophenyl, hydroxyphenyl and the like. The term "halide" denotes iodide, bromide and chloride.The barbiturates useful for binding to latex polymers are those having free carboxylic acid groups. The barbiturate of particular preference in the practice of the present invention is 5-allyl-5-(1-carboxyisopropyl)barbituric acid (allonalcarboxylic acid) since it has a carboxylic acid group in the sidechain and is readily obtainable. Thus, particularly preferred reagents are aminoaryl esters and amino-lower alkyl amides of the carboxylic acid group of allonalcarboxylic acid. However, the present assay, as hereinafter described, will detect barbiturates with or without free or functionalized carboxylic acid groups, such as barbital, phenobarbital, amobarbital, butabarbital, pentobarbital, etc.The aminoaryl esters and amino-lower alkyl amides of carboxy substituted barbiturates, as described above, are conveniently prepared from carboxy substituted barbiturates. Using allonalcarboxylic acid as an example, one can conveniently introduce the requisite aminoaryl or the amino-lower alkyl moiety by methods well known in the art. Thus, for the preparation of aminoaryl esters of the carboxy substituted barbiturates, one can
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esterify allonalcarboxylic acid with, for example, p-nitrophenol to afford 5-allyl-5-(1-pnitrophenyloxycarbonyl-isopropyl)barbituric acid which one can then reduce to 5propyl-5-(1-p-aminophenyloxycarbonyl-isopropyl) barbituric acid.The esterification is performed in the presence of a condensing agent dissolved in an inert organic solvent. Suitable condensing agents include carbodiimides such as N,N'-diphenylcarbodiimides and N,N'-dicyclohexylcarbodiimides. Suitable inert organic solvents include polar aprotic solvents such as N,N-dimethylformamide, dimethylsulfoxide and hexamethylphosphoramide alone or admixed with non-polar aprotic solvents such as acetone, acetonitrile and ethyl acetate. A particularly preferred condensing agent is N,N'-dicyclohexylcarbodiimide and a particularly preferred organic solvent system is N,N-dimethylformamide-ethyl acetate.The temperature of the esterification reaction is not narrowly critical. The reaction may be carried out between about 0.degree. and 50.degree. C., most preferably at about 0.degree. to 25.degree. C.The reduction is performed by treating the nitroester, so obtained, dissolved in a suitable inert organic solvent, preferably an alkanol such as methanol, ethanol, or 2-propanol, with hydrogen in the presence of a suitable hydrogenation catalyst until the cessation of the uptake of hydrogen. Included among suitable hydrogenation catalysts are platinum, palladium, rhodium, ruthenium and nickel, unsupported or supported on carriers such as carbon, silica, alumina and the like. A particularly preferred hydrogenation catalyst is 10% palladium-on-carbon. While the temperature and pressure at which the hydrogenation is accomplished is not critical, it is preferred to carry out the reaction at about room temperature and about atmospheric pressure.For the preparation of amino-lower alkyl amides of carboxy substituted barbiturates, one can aminate allonalcarboxylic acid with, for example, 1,4-diaminobutane to afford 5-allyl-5-[1-(4-aminobutylcarbamoyl)isopropyl]barbituric acid.The amination is performed in the presence of a condensing agent dissolved in an inert organic solvent. Suitable condensing agents include carbodiimides such as N,N'-diphenylcarbodiimide and N,N'-dicyclohexylcarbodiimide and carbonyldiimidazoles such as 1,1'-carbonyldiimidazole. Suitable inert organic solvents are ethereal solvents such as monoglyme, diglyme, dioxane and tetrahydrofuran. A particularly preferred condensing agent is 1,1'-carbonyldiimidazole. A particularly preferred inert organic solvent is tetrahydrofuran.The temperature at which the amination is carried out is not narrowly critical. A reaction temperature within the range of about 0.degree. to about the boiling point of the solvent is preferred, a reaction temperature of about 25.degree. C. being most preferred.The carboxy substituted barbiturates are also conveniently prepared by methods well known to a chemist of ordinary skill in the art. For example, the carboxy substituted barbiturates can be readily prepared by reductive alkylation of barbituric acid with an aldehydo- or keto-ester followed by alkylation and saponification of the ester group of the resulting 5,5-disubstituted-barbituric acid.The reductive alkylation is conducted by treating barbituric acid and an aldehydo- or keto-ester such as ethyl formylacetate, ethyl acetoacetate and ethyl levulinate, with hydrogen in the presence of a metal hydrogenation catalyst to afford a 5-monosubstituted barbituric acid derivative. Suitable metal catalysts are nickel and the nobel metals such as platinum, palladium, rhodium, ruthenium and so forth. The catalysts are normally employed in finely divided form and may be either unsupported or present on a suitable inert carrier such as carbon, aluminum, silica, calcium carbonate and the like. A particularly preferred catalyst is 10% palladium-on-carbon.As solvents for the reductive alkylation, there may be mentioned alcohols such as methanol, ethanol, 2-propanol and the like, and esters such as ethyl acetate and so forth.While the reductive alkylation may be performed over a wide range of temperatures and pressures from, for example, about room temperature to about 150.degree. C. and about atmospheric pressure to about 1000 psi, it is preferable to employ a reaction temperature of about 90.degree. to about 100.degree. C. and a
Patents 45
pressure of about 700 psi.The alkylation step is accomplished by treating the monosubstituted barbituric acid derivative with an alkylating agent such as methyl halide, propyl halide, allyl halide, hexyl halide, cyclohexenyl halide and the like, in a suitable inert solvent in the presence of a base to afford a 5,5-disubstituted barbituric acid derivative. Suitable solvents include, among others, alcohols such as methanol, ethanol, 2-propanol and the like, water and mixtures of water and alcohols. Suitable bases are alkali metal and alkaline earth hydroxides such as sodium and potassium hydroxide and calcium hydroxide, and alkali metal alkoxides such as sodium methoxide, potassium ethoxide and potassium tertiary-butoxide. A particularly preferred base and solvent system is about 20% aqueous sodium hydroxide. The alkylation may be conducted over a temperature range of from about 10.degree. to about 80.degree. C., most preferably between about 25.degree. to 60.degree. C.The saponification step is conducted by treating the disubstituted barbituric acid derivative with an aqueous acid such as hydrochloric acid, hydrobromic acid, dilute sulfuric acid and the like, at an elevated temperature. For this conversion, aqueous hydrochloric acid having a normality of about 1 and a reaction temperature of about the reflux temperature of the reaction mixture is preferred.In order to prepare the diagnostic reagent useful for the practice of the present invention, aminoaryl esters and aminolower alkyl amides of carboxy substituted barbiturates are covalently bonded by means of an amide linkage to a latex polymer containing carboxyl groups.Suitable latex polymers for this purpose are carboxylated styrene butadienes, carboxylated polystyrenes, acrylic acid polymers and the like. Among the commercial latex polymers which are included in the aforementioned classes are Dow 421, Dow 816, Dow 620, Fluka 241 and Dow 241. Dow batch 1721, a latex polymer of the polystyrene type having a particle size of about 0.2 to about 0.3 microns, percent solid composition of about 8 to about 12% and a specific gravity of about 1.02, is also suitable.Particularly preferred polymers are carboxylated styrene butadiene copolymers, preferably Fluka 241 or Dow 241. Suitable latex carrier particles are generally supplied commercially as an aqueous latex suspension, usually in concentrations of about 5 to about 60% solids. These polymers are water insoluble, have a particle size in the range from about 0.01 to about 0.9 microns, preferably between about 0.1 and about 0.3 microns, and a specific gravity near that of water enabling them to remain in aqueous suspension. The particles should have sufficient surface charge density so that when coupled to the aminoaryl esters and amino-lower alkyl amides of carboxy substituted barbiturates, their repulsive forces are enough to prevent aggregation.The aminoaryl esters and amino-lower alkyl amides of carboxy substituted barbiturates are coupled to the carboxylated latex polymers by means of an amide linkage initiated in the presence of a water soluble carbodiimide condensing agent. The degree of coupling is dependent upon the density of the reactive groups in the polymer. The density of the reactive groups is not critical to the operability of this invention, as long as a sufficient number of reactive groups are present to provide coupling of a sufficient amount of barbiturate moiety to be useful in a diagnostic test. However, a suitable density would be in the range of from about 1 to about 5%, preferably about 3%, by weight. The coupling reaction with carbodiimides is described in detail in U.S. Pat. No. 3,857,931.Once the latex coupled product is formed, it can be utilized in specific diagnostic tests for the detection of barbiturates. It can be used in any convenient concentration, depending upon the specific test and samples involved. However, concentrations of from about 0.1 to about 2% by weight of latex solids are suitable and the preferred concentrations are from about 0.3 to about 1.5% by weight.In a typical test, a measured amount of antiserum against barbiturates is mixed with a barbiturate free body fluid, for example, serum, saliva or urine. Then, a measured amount of aminoaryl or amino-lower alkyl barbiturate coupled latex is added and the mixture is allowed to incubate at a slightly elevated temperature, e.g., 37.degree. C., for
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a period of time, for example, from about 1 to about 3 hours, preferably for about 2 hours. The pH of the text mixture is suitably in the range of from about pH 5.0 to 8.5, most preferably about 6.5 to 7.5. After the incubation, flocculation or agglutination of the latex particles is noted. The concentration and quantity of both the antiserum and the latex complex are adjusted to produce a strong flocculation, and the minimum concentrations of both reagents which produce a strong flocculation are determined. The mixture of antiserum against barbiturate and barbiturate free body fluid may be incubated at a slightly elevated temperature, e.g., 37.degree. C., prior to the addition of the aminoaryl or amino-lower alkyl barbiturate coupled latex.The antisera which may be used in the present diagnostic test are antisera specific for barbiturates, such as secobarbital and pentobarbital. The preparation of such antisera is described in U.S. Pat. No. 3,766,162 and in Science, 174, 1037 (1971).After the control system is set up, as described above, various amounts of barbiturates, e.g., secobarbital, pentobarbital, butabarbital, amobarbital, phenobarbital and barbital are dissolved in barbiturate free body fluid. The minimum amount of barbiturate required to inhibit the flocculation is noted. This quantity will depend both upon the concentration and the amount of body fluid added, as well as upon the concentration and the strength of the antiserum utilized in the test.In a preferred test, the quantities and concentrations are adjusted so that approximately 400-500 microliters of serum or urine containing between about 100 and 200 nanograms of barbiturate per milliliter (total of between 40-50 and 80-100 nanograms of barbiturate) will be just sufficient to inhibit flocculation. Once the test has been standardized with one type of body fluid, for example, urine, another type of body fluid, for example, serum, should not be substituted, and a separate standard must be set up for this.Since the presence of flocculation is easily visualized by the naked eye, the present test serves as an extremely sensitive assay method for the detection of barbiturates, such as secobarbital, pentobarbital, butabarbital, amobarbital, phenobarbital and barbital. Thus, once the test has been standardized as mentioned above, the presence of nanogram quantities of these barbiturates in body fluids can easily be detected by noting the inhibition of flocculation caused by the presence of such barbiturates in the body fluid, as compared with the flocculation resulting when barbiturate free body fluid is employed.The test can be standardized so that a medically and statistically meaningful cut-off point is established. Thus, quantities of barbiturates in body fluid greater than this amount will cause inhibition of flocculation (a positive test for the presence of such drug in the body fluid) and quantities less than this amount will not inhibit flocculation (a negative test).The above described reagents can be conveniently packaged for commercial purposes, e.g., in a diagnostic reagent kit containing two separate containers: one with the antiserum against barbiturates and the other with the aminoaryl esters or amino-lower alkyl amides of carboxy substituted barbiturates bonded via an amide linkage to latex particles containing carboxyl groups, most preferably in aqueous suspension.The aminoaryl esters and amino-lower alkyl amides of carboxy substituted barbiturates can also be linked to immunogenic carrier materials such as proteins or polypeptides by means of an amide linkage to afford antigens which are useful for the elicitation of antibodies specific for barbiturates. The method of linkage to immunogenic carrier materials, as well as the elicitation of antibodies, are generally described in U.S. Pat. No. 3,766,162.The invention is further explained and illustrated in the following examples. All temperatures are in degrees Centigrade. Excerpt(s): A mixture of 200 g. of barbituric acid, 215 g. of ethyl acetoacetate, 10 g. of 10% Pd-C and 400 ml. of methanol was placed into a 2 liter glass lined reaction vessel and hydrogenated at 90.degree.-100.degree. and 700 psi for 20 hours. Two liters of water were added to the suspension and the mixture was heated to effect solution. The catalyst
Patents 47
was removed by filtration and the filtrate was cooled overnight. The crystals were collected to yield 209 g. of the ester, m.p. 160.degree.-162.degree. The mother liquor was evaporated in vacuo and the residue was suspended, with stirring, in a small volume of boiling ethyl acetate. The solution was allowed to cool to room temperature and unreacted barbituric acid was collected. An additional 65.2 g. (total yield 87.6%, based on recovered barbituric acid) of the ester was obtained from the filtrate. It had mp. 160.degree.-162.degree. Into a one liter three-neck flask equipped with mechanical stirrer, reflux condenser and a dropping funnel, were placed 100 g. of 5-(1ethoxycarbonylisopropyl)barbituric acid, 100 mg. of calcium sulfate, 50 mg. of copper dust and 500 ml. of water. The mixture was stirred at room temperature for 15 minutes and 53.6 g of allyl bromide were added in one portion followed by the dropwise addition of 125 ml. of 20% sodium hydroxide over 45 minutes at 50.degree.-55.degree. After stirring at 50.degree.-55.degree. for 3 hours, the reaction mixture was cooled to about 30.degree. and an additional 26.8 g. of allyl bromide were added in one portion. The reaction mixture was heated with stirring, for 90 minutes, and a solution (65-70 ml.) of 20% sodium hydroxide was then added at a rate such that the reaction mixture was always slightly alkaline. The mixture was cooled to room temperature. The pH of the mixture was adjusted to about 9 by the addition of 20% sodium hydroxide and the mixture was extracted with 4.times. 250 ml. of ethyl acetate. The combined ethyl acetate extracts were re-extracted with 4.times. 300 ml. of 1% sodium hydroxide and the aqueous extracts were added to a mixture of 500 g. of ice and 300 ml. of 6N hydrochloric acid. The precipitate which formed upon standing at room temperature overnight was collected to give 91.0 g. (78%) of the alkylbarbituric acid, m.p. 112.degree.-114.degree. A mixture of 50 g. of 5-allyl-5-(1-ethoxycarbonyl-isopropyl)barbituric acid and 400 ml. of 1N hydrochloric acid was heated under reflux for 4 hours. The solution was allowed to stand at room temperature overnight and the precipitate was collected to yield 42.5 g. (94%) of the acid, m.p. 202.degree.-203.degree. Web site: http://www.delphion.com/details?pn=US04101549__ •
Barbiturate assay compositions and methods Inventor(s): Grote; Jonathan (Grayslake, IL), Hu; Hsiang (Libertyville, IL) Assignee(s): Abbott Laboratories (abbott Park, Il) Patent Number: 5,096,838 Date filed: November 27, 1989 Abstract: The present invention provides methods and compositions for assaying biological samples, such as human serum, for barbiturates. In one aspect, analogs of barbiturates derivatized with fluorescein and analogs of barbiturates derivatized with immunogenic polypeptides are provided. The fluorescent analogs are employed as tracers in a competitive homogeneous immunoassay, i.e., a fluorescence polarization immunoassay, for detecting barbiturates. The immunogenic analogs are employed to make anti-barbiturate antiserum of the invention for use in the immunoassay method. Intermediates for preparing the fluorescent and immunogenic analogs are also provided. Further provided are test kits, comprising a fluorescent tracer and an antiserum according to the invention, for analyzing biological samples by fluorescence polarization immunoassay for the presence of a barbiturate. Further, an improvement is provided in immunoassays for analytes in serum, wherein a transfer means, such as a pipette, is used repeatedly to transfer different samples into the assay system. In the improvement, an aqueous solution of specified composition, comprising
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dimethylsulfoxide and an alkali halide, is used to wash the transfer means between transfers. Excerpt(s): The present invention relates to immunoassays and, more particularly, to novel compounds and antisera for use in fluorescence polarization immunoassays for barbiturates, novel methods of using the compounds and antisera, and novel intermediates for making the compounds and antisera. The invention also concerns an improvement in immunoassays for analytes in serum samples. The barbiturates are a class of synthetic drugs commonly prescribed as sedatives, hypnotics, and anticonvulsants. These drugs produce depression of the central nervous system ranging from mild sedation to coma. The degree of depression depends upon the type of barbiturate, the amount consumed, the method of administration of the barbiturate, and the state of excitability of the nervous system of the individual taking the drug. Excessive use of barbiturates may lead to habituation or addiction. Overdose on, or abrupt withdrawal from, barbiturates can cause coma or even death. Web site: http://www.delphion.com/details?pn=US05096838__ •
Barbiturate derivatives and protein and polypeptide barbiturate derivative conjugates and labels Inventor(s): Buechler; Kenneth F. (San Diego, CA) Assignee(s): Biosite Diagnostics, Inc. (san Diego, Ca) Patent Number: 5,414,085 Date filed: April 6, 1992 Abstract: The present invention is directed to novel barbiturate derivatives which are synthesized for the covalent attachment to antigens (proteins or polypeptides) for the preparation of antibodies or receptors to the barbiturate metabolites. The resulting novel antigens may be used for the production of antibodies or receptors using standard methods. Once generated, the antibodies or receptors and the novel derivatives which are covalently attached to proteins, polypeptides or labels may be used in the immunoassay process. Excerpt(s): This invention is in the field of ligand receptor assays, including immunoassays, for the detection of selected metabolites of barbiturates in a fluid sample. More particularly, this invention relates to methods for the synthesis of novel barbiturate derivatives and protein and polypeptide barbiturate derivative conjugates and labels for use in the preparation of antibodies to barbiturate metabolites and for use in the immunoassay process. The class of barbiturate derivatives is extensive and in general they are characterized by the amide urea ring with various alkyl substituents off the 5' position. Barbiturates are used as sedatives, hypnotics and to control seizures. The class of barbiturates includes, but is not limited to, amobarbital, aprobarbital, barbital, butabarbital, mephobarbital, pentobarbital, phenobarbital and secobarbital. The illicit and excessive use of barbiturates has resulted in a medical need for antibodies and diagnostics to rapidly detect the barbiturate metabolites in order to monitor and treat barbiturate addiction. The preparation of antibodies to barbiturate metabolites requires the synthesis of a barbiturate derivative in order to covalently attach the derivative to an antigenic polypeptide or protein. In addition, the barbiturate derivative is covalently attached to various polypeptides, proteins or labels for use in screening antibodies and in the immunoassay process. The barbiturate derivative should mimic the structure of the class of barbiturate metabolites sought to be measured. Therefore, the selection and
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synthesis of the types of barbiturate derivatives for covalent attachment to proteins, polypeptides or labels is critical. In addition, the barbiturate derivatives need to be stable and soluble in an aqueous solution. Web site: http://www.delphion.com/details?pn=US05414085__ •
Barbiturates as safening agents in conjunction with NMDA antagonists Inventor(s): Olney; John W. (1 Lorenzo La., Ladue, MO 63124) Assignee(s): None Reported Patent Number: 5,474,990 Date filed: July 22, 1991 Abstract: Certain barbiturates have been shown to completely prevent the neurotoxic injury to cerebrocortical neurons that can be caused by NMDA antagonists. The use of barbiturates as "safening agents" allows NMDA antagonists (including powerful NMDA antagonists such as MK-801) to be used safely as neuroprotectants to prevent brain damage due to hypoxia/ischemia caused by strokes, cardiac arrest, perinatal asphyxia, and various other conditions. Excerpt(s): This invention is in the fields of pharmacology and neurology. It relates to two different classes of receptors on the surfaces of neurons, known as NMDA receptors, which are triggered by N-methyl-D-aspartate (NMDA), and GABA receptors, which are triggered by gamma-aminobutyric acid (GABA). This invention involves the use of NMDA antagonists (i.e., agents which block activity at NMDA receptors) as therapeutic agents which can prevent excitotoxic brain damage and nerve cell death during stroke, cardiac arrest, perinatal asphyxia, drowning, and various other events. Unfortunately, the currently available NMDA antagonists, when used for such purposes, exert toxic side effects that can kill or permanently damage neurons in certain regions of the brain. This invention relates to the discovery that certain types of barbiturates which function as GABAmimetic agents (i.e., they trigger activity at GABA receptors) function as "safening agents" to reduce the damaging side effects of NMDA antagonists. By reducing the damage caused by NMDA antagonists, the barbiturates disclosed herein allow the safe use of NMDA antagonists to treat stroke, cardiac arrest, and other conditions. Web site: http://www.delphion.com/details?pn=US05474990__
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Composition for antagonizing the narcotic effects of barbiturate addiction and withdrawal effects, and for treatment of barbiturate poisoning Inventor(s): Penn; Nathar W. (463 Glendale Road, Wyckoff, NJ 07481) Assignee(s): None Reported Patent Number: 4,048,316 Date filed: March 4, 1974 Abstract: The invention is based on the discovery, after long study and many test operations, that the combination of five chemical elements, towit 5hydroxymethylcytosine, thymine, nicotamide, pyridoxal, and thiamine, is effective in antagonizing the narcotic effects of barbiturates, and that each one is essential, in the combination, for positive result. Although thymine per se long has been known as
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increasing the action of barbiturates, tests of the said composition established that thymine has an unexpected and essential function therein, its omission rendering the composition ineffective. These tests were directly made by the present applicant, with corroboration as to every detail thereof by the Chief of the Section of Neurochemistry, New York State Institute of Neurochemistry and Drug Addiction, established by the State of New York, and operating under its control. Excerpt(s): Barbiturates are in three classes, towit: ultra-short acting, long acting, and intermediate. Although it is generally accepted that substances which antagonize one barbiturate will antagonize another, tests, as referred to above, show full effectiveness of the present composition with each of the barbitol classes. towit: the ultra-short acting, exemplified by hexobarbital; the long-acting, exemplified by phenobarbital; and the intermediate acting, exemplified by pentobarbital. The tests were made in accordance with practice now accepted as determining the effectiveness of materials for antagonizing drugs in man, and for chemicals, and also for antagonizing carcinomas, by tests on mice or rates, examples being cited in the footnote below **. ** 1. Drs. Cohn, Taylor & Yamakaya, Pittsburgh University School of Medicine July 30, 1973, Research Communications in Chemical Pathology and Pharmacology, Vol. 6, No. 2, pp 435-443 "A major aim of this research is to determine the basis for the use of dibutryl cylcic in man" 2. Drs. Silbergeld and Goldberg, to investigate the result of lead acetate in children, by treatment of a mitigating material on mice -- The Johns Hopkins University School of Hygiene and Public Health; Life Sciences, Vol. 13. pp. 1275-1283 September 1973. U.S. Pat. No. 3,577,558, etc. Web site: http://www.delphion.com/details?pn=US04048316__ •
Compositions and methods for treating wrinkles and/or fine lines of the skin Inventor(s): Breton; Lionel (Versailles, FR), De Lacharriere; Olivier (Paris, FR) Assignee(s): L'oreal (paris, Fr) Patent Number: 5,869,068 Date filed: October 2, 1995 Abstract: Compositions which contain an agonist substance of one or a number of receptors associated with a chlorine channel are useful for slackening and/or relaxing cutaneous tissue, and in particular for the purpose of treating wrinkles and fine lines of the skin. Such compositions can be administered topically or by injection. Preferred agonists include glycine, serine, taurine,.beta.-alanine, N-(benzyloxycarbonyl)glycine (Z-glycine), gamma-aminobutyric acid (GABA), isoguvacine, isonipecotic acid, 4,5,6,7tetrahydroisoxazolo›5,4-c!pyrid-3(2H)-one, benzodiazepines, steroids, and barbiturates. The composition can additionally contain a retinoid and/or a hydroxy acid. Excerpt(s): The present invention relates to the use of substances which are agonists of a receptor associated with a chlorine channel in a cosmetic and/or dermatological composition, in particular for the purpose of treating wrinkles and fine lines of the skin, and to cosmetic and/or dermatological compositions which contain such a substance. Women, and indeed even men, are currently inclined to wish to appear young for as long as possible and consequently are looking to soften the signs of ageing of the skin, which are reflected in particular by wrinkles and fine lines. In this respect, advertising and fashion present products intended to retain a radiant and wrinkle-free skin, these being the signs of young skin, for as long as possible, all the more so since physical appearance has an effect on mental attitude and/or on morale. It is consequently
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important to feel physically and spiritually young. Until now, wrinkles and fine lines have been treated using cosmetic products containing active agents which act on the skin, for example by moisturizing it or by improving its cell renewal or alternatively by promoting the synthesis of collagen of which the cutaneous tissue is composed. However, to date, it is not known to act on wrinkles by involving the muscle components present in the skin. Web site: http://www.delphion.com/details?pn=US05869068__ •
Flame resistant plastics containing guanidine barbiturates or guanidine thiobarbiturates, and also guanidine barbiturates and guanidine thiobarbiturate Inventor(s): Horacek; Heinrich (Puchenau, AT) Assignee(s): Chemie Linz Gesellschaft M.b.h. (at) Patent Number: 5,373,038 Date filed: April 20, 1993 Abstract: Flame resistant plastics that contain guanidine barbiturates, guanidine thiobarbiturates or their mixtures as flame retardants, and also guanidine barbiturate and guanidine thiobarbiturate. Excerpt(s): The present invention relates to plastics that contain guanidine barbiturates or guanidine thiobarbiturates in order to improve their flame resistance, to a process for improving the flame resistance of plastics by adding guanidine barbiturates or guanidine thiobarbiturates, and also to guanidine barbiturate and guanidine thiobarbiturate. Although the halogen-containing flame retardants normally used exhibit a good action, they suffer from the serious disadvantage that in the event of a fire, especially in the event of a prolonged fire, they release toxic and corrosive chlorine and bromine compounds. Halogen-free flameproofing agents, for example melamine or melamine cyanurate (U.S. Pat. No. 4,298,518), have been used to obviate these disadvantages. Melamine has, inter alia, the disadvantage that it tends to bloom when the plastics are processed, which means that in some cases it migrates to the surface and leaves an objectionable film for example in injection molds. Melamine cyanurate tends to sublime on incorporation into the plastic, the latter foaming somewhat and the bulk density being reduced. It is an object of the present invention to provide novel substances that are suitable as flame retardants for plastics. We have surprisingly found that guanidine barbiturates and guanidine thiobarbiturates have a good flame retardant action on plastics. Web site: http://www.delphion.com/details?pn=US05373038__
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Labeled drug hapten analogues for immunoassays Inventor(s): Brummond; Barbara A. (Rochester, NY), Danielson; Susan J. (Rochester, NY), Hilborn; David A. (Henrietta, NY), Oenick; Marsha D. B. (Rochester, NY), Ponticello; Ignazio S. (Pittsford, NY) Assignee(s): Eastman Kodak Company (rochester, Ny) Patent Number: 5,298,403 Date filed: March 16, 1992
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Abstract: The invention is directed to labeled drug hapten analogues comprising:(A) a label, of the type used in immunoassays, having an amine or sulfhydryl group;(B) a drug hapten nucleus selected from barbiturates or hydantoins and(C) a linking chain linking the 3-position of the drug hapten nucleus to the label through a carbonyl bridge. Excerpt(s): This invention relates to clinical chemistry particularly immunoassays. Immunoassays, which take advantage of natural immunological reactions, have found wide-spread use as analytical techniques in clinical chemistry. Because of the specificity of the reactions, they are particularly advantageous in quantifying biological analytes that are present in very low concentration in biological fluids. Such analytes include, for example, antibodies, therapeutic drugs, narcotics, enzymes, hormones, proteins, etc. Conventional labels include radioactive tags, enzymes, chromophores, fluorophores, stable free radicals, and enzyme cofactors, inhibitors and allosteric effectors. Web site: http://www.delphion.com/details?pn=US05298403__ •
Pharmaceutical for the treatment of sleep disorders Inventor(s): Metz; Gunter (Blaubeuren, DE), Rauchle; Kurt (Blaubeuren-Sonderbuch, DE) Assignee(s): Merckle Gmbh (blaubeuren, De) Patent Number: 4,505,914 Date filed: July 29, 1983 Abstract: At least one barbiturate or one of its pharmaceutically acceptable salts is combined with cinnarizine or flunarizine or one of their pharmaceutically acceptable salts to provide a hypnotic requiring lower dosages of barbiturates to produce the same effect as the barbiturate alone. Excerpt(s): The invention relates to a pharmaceutical for the treatment of sleep disorders, which contains lower dosages of barbiturates in combination with cinnarizine and/or flunarizine. Among the therapeutically employed hypnotics, barbiturates still hold a central position today. Among the disadvantages of their use is, among others, the need of a higher dosage, which, depending upon the barbiturate, requires single doses of 150 mg to about 650 mg. In the literature, different materials are known which can increase the effect of barbiturates. Thus, Dimercaprol (BAL) checks the decomposition of pentobarbital [J. Pharmacol. Exp. Therap. 109, 292 (1953)], also tocopherol increases the effect of barbiturates [Arch. Int. Pharmacodyn. Therap. 97, 473 (1954)]. In addition it is known that strong antihistamines (phenothiazines) and tranquilizers (Meprobamate), have a pontentiating or enhancing effect on barbiturates. Under the usual combinations of barbiturates with sedatives and other hypnotics, which are registered in the list of traded drugs in Germany, there are still few representatives of these two groups. It has now been surprisingly found that cinnarizine and flunarizine have a potentiating or enhancing effect on the action of barbiturates and these combinations have new pharmacological properties. Cinnarizine (1-benzhydryl-4trans-cinnamylpiperazine or 1-cinnamyl-4-diphenylmethylpiperazine) is known from German Pat. No. 1,086,235. Cinnarizine and also its difluorinated structural analog, flunarizine, have only weak antihistaminic properties and are used therapeutically as peripheral and cerebral vasodilators. Web site: http://www.delphion.com/details?pn=US04505914__
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Process for the production of 2-(methylthio)-disodium barbiturate Inventor(s): Etzensperger; Marcel (Gamsen, CH), Roduit; Jean-Paul (Sierre, CH), Wellig; Alain (Ried bei Morel, CH) Assignee(s): Lonza, Ltd. (gampel/valais, Ch) Patent Number: 5,250,689 Date filed: August 27, 1992 Abstract: A process for the production or 2-(methylthio)-disodium barbiturate. Thiourea, malonic acid dimethyl ester and sodium methanolate are reacted to disodium thiobarbiturate. The disodium thiobarbiturate then is reacted with methyl bromide, optionally in the presence of a base, to the end product. Excerpt(s): 2-(Methylthio)-disodium barbiturate is an important intermediate product for the production of the herbicide difluoromethyl thiobarbiturate (U.S. Pat. No. 4,692,524). The production of monosodium thiobarbiturate starting from malonic acid dimethyl ester, thiourea and sodium methanolate is known. These three initial materials are used in an approximately molar ratio of 1:1:1 (European Published Patent Application No. 411,277). In addition the next stage, that is, the methylation of this monosodium thiobarbiturate with methyl bromide to 2-(methylthio)-barbituric acid, is known and this reaction is performed under increased pressure (European Published Patent Application No. 411,276). A drawback of this two-stage synthesis for the production of 2-(methylthio)-barbituric acid is that in the first stage the monosodium thiobarbiturate is formed, and then, in the next stage, the latter reacts only under increased pressure and higher temperature with methyl bromide to 2-(methylthio)barbituric acid. A further drawback is that 2-(methylthio)-barbituric acid cannot be converted directly into difluoromethyl thiobarbituric acid but only by an intermediate stage. Web site: http://www.delphion.com/details?pn=US05250689__
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Specific binding assay method and reagent means Inventor(s): Cais; Michael (Haifa, IL) Assignee(s): Technion Research & Development Foundation Ltd. (haifa, Il) Patent Number: 4,205,952 Date filed: May 10, 1977 Abstract: A method and reagent means for the determination of small quantities of chemical compounds in man, animal and plants by a specific binding assay technique.The method involves the utilization of a labelling constituent comprising a conjugate of a labelling substance and a binding component said labelling substance being one or more metal atoms which can be easily determined. The labelling constituents are selected from various metalo organic derivatives or metal coordination complexes.The method is very specific and sensitive and can be successfully utilized for the determination of haptens selected from various groups such as alkaloids, barbiturates, steroids, cannabinoids, vitamins, aminoacids, tranquilizers, sugars, penicillins, etc. Excerpt(s): The present invention relates to a new method and reagent means for the determination of the presence of small quantities of chemical compounds. More specifically the invention relates to an accurate, efficient and specific analysis of small
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quantities of chemical compounds in man, animals and plants by a specific binding assay technique. Today there is a continuous demand for rapid and accurate quantitative determinations of chemical substances present in very low concentrations in body fluids such as blood, saliva or urine. These chemical substances can derive either from naturally occurring physiologically active compounds or from ingested drugs and/or their metabolites. These drugs belong either to the class of compounds administered medically for therapeutic purposes or they can be drugs of abuse such as narcotics and other poisoning materials. Of most importance is the determination for diagnostic purposes of particular compounds which may be indicative of the proper function, or otherwise, of body processes. Also for instance in case of poisoning, an easy and rapid method for determining the toxin could be extremely important in order to provide the required antidote. Obviously, one of the demands of these determinations is the specificity of the assay to be free of interferences by other components of the sample taken for analysis. Actually this is the main disadvantage of a large number of known techniques such as ultraviolet and visible spectrophotometers, fluorometers, mass spectrophotometer, chromatographic methods, wherein various degrees of nonspecificity and interferences cause that these techniques could not be practically applicable. A recent special issue of the Journal of Chromatographic Science, 1974, (volume 12, p. 209-336) devoted to the "Analysis of Drugs of Abuse" reviews in a very concise manner the state of the art of the various methods. The development of analytical methods incorporating specific binding assay techniques ino the area of assaying liquids, such as biofluids, for ligands, such as drugs of abuse, has resulted in highly increased levels of sensitivity of detection. Among the known methods, the following four specific binding assay techniques can be mentioned: Radio immunoassay (R I A), free radical assay technique (FRAT), hemaglutination inhibition (HI) and enzyme multiplied immunoassay technique (EMIT). Specific binding assays are based on the principles of monitoring specific binding reactions in which the extent of binding is a function of the amount of unknown ligand present by means of a labelled component. Web site: http://www.delphion.com/details?pn=US04205952__ •
Treatment with combined NMDA and non-NMDA antagonists to reduce excitotoxic CNS damage Inventor(s): Olney; John W. (St. Louis, MO) Assignee(s): Washington University (st. Louis, Mo) Patent Number: 5,834,465 Date filed: May 1, 1992 Abstract: This invention involves a pharmaceutical mixture for preventing or reducing excitotoxic brain damage caused by hypoxia/ischemia (such as stroke) and various other factors. This mixture comprises an NMDA antagonist and a non-NMDA antagonist, both of which penetrate blood-brain barriers (BBB's) and which, in combination, provide greater protection against excitotoxic damage than can be provided by any quantity of either agent by itself. Suitable NMDA antagonists can be either competitive antagonists which bind directy to the NMDA binding site in the NMDA receptor complex, or non-competitive agents that interact with other binding sites such as the PCP, glycine, or polyamine binding sites. Suitable non-NMDA antagonists include a quinoxalinedione compound referred to as NBQX, and a 2,3benzodiazepine compound referred to as GYKI 52466. If an NMDA antagonist is used
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which is stronger than dextromethorphan, the mixture of an NMDA and a non-NMDA antagonist preferably should be administered in combination with a third agent that functions as a "safening agent" to prevent or reduce the neurotoxic side effects caused by strong NMDA antagonists. Two classes of safening agents have been identified: (1) anticholinergic agents such as scopolamine and, (2) barbiturates which act as direct agonists of gamma-amino-butyric acid (GABA) receptors, such as secobarbital, pentobarbital, and thiamylal. Excerpt(s): This invention pertains to neurology and neuropharmacology. It describes methods and compounds which are safer and more effective than others currently available for protecting the brain against acute damage in conditions such as stroke, epilepsy, and physical trauma. Since glutamic and aspartic acid are amino acids, this neurotransmitter system is called the excitatory amino acid (EAA) system. In order to transmit a nerve signal or impulse from one neuron to another, a neuron releases glutamate or aspartate into the fluid which fills the synaptic gap between the transmitting neuron and the receiving neuron. A molecule of glutamate or aspartate reacts with a receptor on the surface of the receiving cell, thereby causing the opening of an ion channel which allows calcium and sodium ions to enter the cell. The flow of ions into the cell provokes several reactions; typically, the excited neuron transmits the nerve impulse to other neurons, by releasing glutamate at some or all its own synapses. A molecule of glutamate or aspartate does not bond to an EAA receptor; instead, it immediately disengages from the receptor and returns to the fluid in the synaptic gap between the transmitting neuron and the receiving neuron. Web site: http://www.delphion.com/details?pn=US05834465__ •
Use of C-5 mono-substituted barbiturates to treat disorders of uric acid metabolism Inventor(s): Warrell, Jr.; Raymond P. (New York, NY) Assignee(s): Memorial Hospital for Cancer and Allied Diseases (new York, Ny) Patent Number: 4,880,811 Date filed: June 24, 1987 Abstract: The present invention provides a method for decreasing the bodily content of uric acid in a subject which comprises administrating to the subject an effective contentdecreasing amount of a barbiturate compound mono-substituted at the carbon-5 position.The invention also provides a pharmaceutical composition and a method for treating disorders of uric acid metabolism and resulting ailments in a subject. Excerpt(s): Throughout this application various publications are referenced and citations are provided in parentheses for them. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art to which this invention pertains. Disorders of uric acid metabolism are extremely common. These disorders may afflict 1% or more of human individuals (Hall, A. P., et al., Am. J. Med. 42: 27, 1967; Heine, J., Virchow's Arch. f. Path. Anat., 260: 521, 1926; Decker, J. L. et al., Arth. Rheum. 5: 144, 1962). The best known example is gout which causes a painful, chronic arthritis which can be extremely debilitating and can lead to extensive deformities (Wyngarden, J. B. and Kelly, W. N., The Metabolic Basis of Inherited Disease, 916-1010, J. B. Stanbury, J. B. Wyngarden, D. S. Fredrickson, 4th ed. McGraw-Hill: New York, 1978; Bauer, W. and Krane, S. M., Disease of Metabolism, 805-849, G. G. Duncan, 5th ed., Saunders: Philadelphia, 1964). Gout may be primary or secondary. Primary gout consists of hereditary diseases which are
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associated with increased serum uric acid levels (hyperuricemia). Secondary gout may occur in cancers, particularly leukemias, and in other blood disorders (e.g. polycythemia, myeloid metaplasia, etc.). There exists abundant evidence that prolonged elevations of serum uric acid are associated with the deposition of sodium urate crystals in many tissues, including kidney and joints. Web site: http://www.delphion.com/details?pn=US04880811__ •
Uses of xanthine compounds Inventor(s): Fukunaga; Alex S. (1030 El Monte Ave., Mountain View, CA 94040), Fukunaga; Atsuo F. (5411 Littlebow Rd., Rancho Palos Verdes, CA 90275) Assignee(s): None Reported Patent Number: 6,025,362 Date filed: August 31, 1998 Abstract: Xanthine compounds are utilized to accelerate anesthetic recovery from the effects of certain compounds as propofol, etomidate, barbiturates, opioids, isoflurane, enflurane, halothane, desflurane, sevoflurane and/or nitrous oxide. In a preferred embodiment, dialkyl substituted xanthines are utilized. Excerpt(s): The present invention is directed to the use of xanthine compounds in medicine, and more particularly to the use of xanthine compounds to counteract the effects of certain classes of drugs. Well known xanthine compounds include theophylline (1,3-dimethyl xanthine; i.e., R.sub.1 and R.sub.2 are CH.sub.3 and R.sub.3 and R.sub.4 are H in the general structure above), theobromine (3,7-dimethyl xanthine; i.e., R.sub.2 and R.sub.3 are CH.sub.3 and R.sub.1 and R.sub.4 are H in the general structure above). Of particular interest to the present invention, are compounds wherein at least two of R.sub.1, R.sub.2, and R.sub.3 are each independently a C.sub.1 -C.sub.4 lower alkyl, including but not limited to the dimethyl and trimethyl substituted forms, such as 1,7-dimethyl xanthine, and 1,3,7-trimethyl xanthine, as well as 8-substituted compounds (e.g., 1,3-dimethyl, 8-phenyl xanthine). For example, xanthine compounds include theophylline and derivatives thereof, including pharmaceutically acceptable salts thereof. Since the aqueous solubility of xanthine compounds tends to be low, reference to xanthine and xanthine compounds referred to herein also includes water soluble derivatives and complexes thereof. For example, the term theophylline includes the water soluble compound aminophylline, which is formed by the combination of theophylline with ethylenediamine (2:1). The present invention arose from the need to find drugs which will counteract the intended effects and/or side-effects of other useful drugs. For the purpose of facilitating the description of the present invention, it is important to appreciate that, despite advances in understanding the molecular basis of drug actions, such as drug-receptor interactions, the mechanisms of action of many drugs that are presently used is not clearly understood. Thus, the difficulty in characterizing the biochemical actions of the drugs in complex physiological systems makes it extremely difficult to develop pharmacologic antagonists to counteract their intended effects and/or side-effects. Furthermore, when drugs with similar pharmacologic effects are administered concurrently, an additive or synergistic response is frequently seen, thereby compounding the problem in antagonizing the effects of the administered drugs. Hence, despite the long felt and great need to develop drugs to counteract the intended effects and/or undesired side-effects of drugs administered for useful purposes, there are few antagonists which enable a physician to achieve a desired
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effect with one drug, and to reverse an intended effect and/or undesired side effects with another drug. This need is particularly strong in the field of anesthesia. Web site: http://www.delphion.com/details?pn=US06025362__
Patent Applications on Barbiturates As of December 2000, U.S. patent applications are open to public viewing.9 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 barbiturates: •
Barbiturates as integrin antagonists and their use for treating inflammatory diseases Inventor(s): Bazin, Marc; (Thiais, FR), Harriman, Geraldine C.; (Charlestown, RI), Kuhn, Cyrille; (Paris, FR), Luly, Jay R.; (Wellesley, MA) Correspondence: Hamilton, Brook, Smith & Reynolds, P.C.; 530 Virginia Road; P.O. Box 9133; Concord; MA; 01742-9133; US Patent Application Number: 20030105119 Date filed: February 22, 2002 Abstract: The invention relates to a pharmaceutical composition comprising a compound of the formula (I): 1in which X is O or S; R1 is hydrogen or -(CH.sub.2).sub.n--Ar1; R2 is hydrogen or has the same meaning as R1; R3 is Ar2 or -(CH.dbd.CH)--Ar2 where Ar2 has the same meaning as Ar1; together with a pharmaceutically acceptable carrier.The invention also relates to a method of treating an individual suffering from a disease associated with leukocyte infiltration of tissues expressing the molecule MAdCAM-1, comprising administering a therapeutically effective amount of a compound of formula (I).The invention also relates to a method of inhibiting the binding of a cell expressing a ligand for MAdCAM-1 on its surface to MAdCAM-1 or a portion thereof.The invention further relates to a method of preparing a pharmaceutical composition comprising a compound of the formula (I). Excerpt(s): This application claims priority to U.S. Provisional Application Serial No. 60/270,503, filed Feb. 22, 2001, entitled "Barbiturates as Integrin Antagonists and Their Use for Treating Inflammatory Diseases." The entire contents of this application are hereby incorporated herein by reference. The present invention relates to barbiturates as integrin antagonists, and their use for treating notably inflammatory diseases. Lymphocyte homing from the circulation to the lymphoid tissues, and migration to sites of inflammation, is regulated by interaction with receptors expressed in postcapillary venules, including high endothelial venules found in secondary lymphoid tissues (e.g. mesenteric lymph nodes, Peyer's patches) (Bevilacqua, M. P., Annu. Rev. Immunol., 11:767-804 (1993); Butcher, E. C., Cell, 67: 1033-1036 (1991); Picker, L. J., et al., Annu. Rev. Immunol., 10:561-591 (1992); and Springer, T A., Cell, 76: 301-314 (1994)). These interactions are tissue specific in nature. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
9
This has been a common practice outside the United States prior to December 2000.
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Enantiomerically pure opioid diarylmethylpiperzine and methods of using same Inventor(s): Chang, Kwen-Jen; (Chapel Hill, NC) Correspondence: Intellectual Property / Technology Law; PO Box 14329; Research Triangle Park; NC; 27709; US Patent Application Number: 20030114462 Date filed: September 25, 2002 Abstract: (-)3-((S)-((2S,5R)-4-Allyl-2,5-dimethyl-1-piperazinyl)(3-thienyl)methyl)ph- enol and pharmaceutically acceptable esters or salts thereof, in essentially enantiomerically pure form have utility as receptor-binding species, e.g., as therapeutic agents for mediating analgesia; as co-administered agents with various other bioactive compositions, including anesthetics, barbiturates, analgesics, etc., for reducing, treating, reversing or preventing drug-mediated respiratory depression that may be directly or indirectly caused by use of such various bioactive compositions; as a conjugate in agonist/antagonist pairs for verifying/assaying receptor and neurotransmitter function; and as a therapeutic agent having utility in combating drug addiction, cardiac disorders, alcohol addiction, drug overdose, cough, lung edema, diarrhea, respiratory, and gastrointestinal disorders. Excerpt(s): The present invention relates to a novel, essentially enantiomerically pure diarylmethylpiperazine compound having utility as a receptor-binding species, e.g., as a mu and/or delta receptor opioid compound mediating analgesia; as a therapeutic agent for co-administration with various other bioactive compositions, including anesthetics, barbiturates, analgesics, etc. for reducing, treating, reversing or preventing drugmediated respiratory depression that may be directly or indirectly caused by use of such various bioactive compositions; as a conjugate in agonist/antagonist pairing for verifying/assaying receptor and neurotransmitter function; and as a therapeutic agent having utility in combating drug addiction, alcohol addiction, cardiac disorders, drug overdose, mental illness, cough, lung edema, diarrhea, respiratory, and gastro-intestinal disorders. In the study of opioid biochemistry, a variety of endogenous opioid compounds and non-endogenous opioid compounds has been identified. In this effort, significant research has been focused on understanding the mechanism of opioid drug action, particularly as it relates to cellular and differentiated tissue opiate receptors. Opioid drugs typically are classified by their binding selectivity in respect of the cellular and differentiated tissue receptors to which a specific drug species binds as a ligand. These receptors include mu (.mu.), delta (.delta.), sigma (.pi.) and kappa (.kappa.) receptors. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Non-sedating barbiturate compounds as neuroprotective agents Inventor(s): Levitt, Barrie; (Mamaroneck, NY), Moros, Daniel A; (Larchmont, NY), Yacobi, Avraham; (Englewood, NJ) Correspondence: Venable, Baetjer, Howard And Civiletti, Llp; P.O. Box 34385; Washington; DC; 20043-9998; US Patent Application Number: 20030153589 Date filed: January 27, 2003
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Abstract: Methods of providing neuroprotection are disclosed comprising administering a non-sedative barbiturate compound in an amount sufficient to achieve neuroprotection in a mammalian subject. Preferred compounds are in the family of diphenylbarbituric acid and analogs. Preferred doses for a neuroprotective effect exceed the dosage of a corresponding sedative barbiturate without sedative side-effects such as anesthesia and death Excerpt(s): The invention relates to the use of non-sedating barbiturate compounds given in a manner and dosage effective to produce blood levels and brain levels of these drugs and/or their active metabolites sufficient to provide a neuroprotectant effect. In particular, the methods and formulations of the invention permit treatment of cerebral ischemia, head trauma and other acute neurologic injuries, and prevention of resulting neuronal damage. Ischemia (stroke) is the third leading cause of death in the United States. When blood supply to the brain is reduced below a critical threshold, a cascade of biochemical events leads to irreversible damage to neurons and brain infarction. Research on treatment and prevention of ischemia is extensive but unfortunately it remains at a basic stage and no adequate therapies are yet in practice (10). Barbiturates in high concentrations have been shown to be neuroprotective in cerebral ischemia in rodents and primates, to reduce the extent of ischemia brain infarction, and to prevent or lessen brain damage (1-4). One theory as to how barbiturates prevent neuronal injury in ischemia is that they inhibit the ischemia-induced uncontrolled release of neurotransmitters, which can attain high, neurotoxic concentrations that cause neuronal death (5). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Pharmaceutical composition and method of modulating cholinergic function in a mammal Inventor(s): Coe, Jotham W.; (Niantic, CT), Sands, Steven B.; (Stonington, CT) Correspondence: Pfizer Inc; 150 East 42nd Street; 5th Floor - Stop 49; New York; NY; 10017-5612; US Patent Application Number: 20030008892 Date filed: March 25, 2002 Abstract: A pharmaceutical composition and method of modulating cholinergic function in a mammal comprising administration of a NRPA compound or a pharmaceutically acceptable salt thereof; and an anti-emetic/anti-nausea agent or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier. The NRPA compound and the anti-emetic/anti-nausea agent are present in amounts that render the composition effective modulating cholinergic function or in the treatment of a diorder or condition selected from inflammatory bowel disease (including but not limited to ulcerative colitis, pyoderma gangrenosum and Crohn's disease), irritable bowel syndrome, spastic dystonia, chronic pain, acute pain, celiac sprue, pouchitis, vasoconstriction, anxiety, panic disorder, depression, bipolar disorder, autism, sleep disorders, jet lag, amyotrophic lateral sclerosis (ALS), cognitive dysfunction, hypertension, bulimia, anorexia, obesity, cardiac arrythmias, gastric acid hypersecretion, ulcers, pheochromocytoma, progressive supranuclear palsy, chemical dependencies and addictions (e.g., dependencies on, or addictions to nicotine (and/or tobacco products), alcohol, benzodiazepines, barbiturates, opioids or cocaine), headache, migraine, stroke, traumatic brain injury (TBI), obsessive-compulsive disorder (OCD), psychosis, Huntington's chorea, tardive dyskinesia, hyperkinesia, dyslexia, schizophrenia, multi-
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infarct dementia, age-related cognitive decline, epilepsy, including petit mal absence epilepsy, senile dementia of the Alzheimer's type (AD), Parkinson's disease (PD), attention deficit hyperactivity disorder (ADHD) and Tourette's Syndrome. The method of using these compositions is also disclosed. Excerpt(s): The present invention relates to pharmaceutical compositions for modulating cholinergic function in a mammal comprising a nicotinic receptor partial agonist compound in combination with an anti-emetic/anti-nausea agent and a pharmaceutically acceptable carrier. The nicotinic receptor partial agonists (NRPAs) included herein are aryl fused azapolycyclic compounds. NRPAs are not limited to those described here. The term NRPA refers to all chemical compounds which bind at neuronal nicotinic acetylcholine specific receptor sites in mammalian tissue and elicit a partial agonist response. A partial agonist response is defined here to mean a partial, or incomplete functional effect in a given functional assay. Additionally, a partial agonist will also exhibit some degree of antagonist activity by its ability to block the action of a full agonist (Feldman, R. S., Meyer, J. S. & Quenzer, L. F. Principles of Neuropsychopharmacology, 1997; Sinauer Assoc. Inc.). The present invention may be used to treat mammals (e.g. humans) for inflammatory bowel disease (including but not limited to ulcerative colitis, pyoderma gangrenosum and Crohn's disease), irritable bowel syndrome, spastic dystonia, chronic pain, acute pain, celiac sprue, pouchitis, vasoconstriction, anxiety, panic disorder, depression, bipolar disorder, autism, sleep disorders, jet lag, amyotrophic lateral sclerosis (ALS), cognitive dysfunction, hypertension, bulimia, anorexia, obesity, cardiac arrythmias, gastric acid hypersecretion, ulcers, pheochromocytoma, progressive supranuclear palsy, chemical dependencies and addictions (e.g., dependencies on, or addictions to nicotine (and/or tobacco products), alcohol, benzodiazepines, barbiturates, opioids or cocaine), headache, migraine, stroke, traumatic brain injury (TBI), obsessive-compulsive disorder (OCD), psychosis, Huntington's chorea, tardive dyskinesia, hyperkinesia, dyslexia, schizophrenia, multiinfarct dementia, age-related cognitive decline, epilepsy, including petit mal absence epilepsy, senile dementia of the Alzheimer's type (AD), Parkinson's disease (PD), attention deficit hyperactivity disorder (ADHD) and Tourette's Syndrome with a decrease in the incidence and severity of unwanted side effects such as nausea and/or stomach upset. The present invention also relates to the combination use of NRPAs and anti-emetic/anti-nausea agents resulting in modulation of cholinergic function without nausea. The combination will provide an improved treatment paradigm than NRPAs alone. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Ultrashort acting hypnotic barbiturates Inventor(s): Druzgala, Pascal; (Santa Rosa, CA), Milner, Peter G.; (Los Altos Hills, CA) Correspondence: Saliwanchik Lloyd & Saliwanchik; A Professional Association; 2421 N.W. 41st Street; Suite A-1; Gainesville; FL; 326066669 Patent Application Number: 20020013330 Date filed: April 24, 2001 Abstract: The subject invention concerns novel compounds that are useful as ultrashort acting hypnotic barbiturates. Specifically exemplified are derivatives of barbituric and thiobarbituric acids. They are rapidly metabolized by blood and tissue enzymes to form polar metabolites with no hypnotic activity and which are rapidly eliminated.
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Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/199,144, filed Apr. 24, 2000. The principal use of a sedative-hypnotic drug is to produce drowsiness and to promote sleep. Since sedative-hypnotic drugs usually have the capacity of producing widespread depression of the CNS, these drugs are employed for various reasons, including as antiepileptic, muscle relaxants, antianxiety drugs, and even to produce amnesia or general anesthesia. Throughout the world, more prescriptions are written for sedative-hypnotic-antianxiety drugs than for any other class of drugs. Barbiturates have enjoyed a long period of extensive use as sedativehypnotic drugs. However, except for a few specialized uses, they have been largely replaced by the somewhat safer benzodiazepines. 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 barbiturates, 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 “barbiturates” (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 barbiturates. You can also use this procedure to view pending patent applications concerning barbiturates. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.
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CHAPTER 6. BOOKS ON BARBITURATES Overview This chapter provides bibliographic book references relating to barbiturates. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on barbiturates include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.
Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print®). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “barbiturates” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “barbiturates” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “barbiturates” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •
Amphetamines, barbiturates, L.S.D. and cannabis: their use and misuse; ISBN: 0113201818; http://www.amazon.com/exec/obidos/ASIN/0113201818/icongroupinterna
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Barbiturates; ISBN: 0877052492; http://www.amazon.com/exec/obidos/ASIN/0877052492/icongroupinterna
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Barbiturates (Encyclopedia of Psychoactive Drugs); ISBN: 0222014571; http://www.amazon.com/exec/obidos/ASIN/0222014571/icongroupinterna
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Barbiturates and Other Depressants (Drug Abuse Prevention Library) by Lawrence Ph.D. Clayton, Ruth C. Rosen (Editor); ISBN: 0823915352; http://www.amazon.com/exec/obidos/ASIN/0823915352/icongroupinterna
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Barbiturates and Your Central Nervous System: The Incredibly Disgusting Story by Susie Derkins; ISBN: 0823933881; http://www.amazon.com/exec/obidos/ASIN/0823933881/icongroupinterna
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•
Barbiturates Sleeping Potion Or Intoxica by Solomon H Snyder (Author); ISBN: 022201458X; http://www.amazon.com/exec/obidos/ASIN/022201458X/icongroupinterna
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Barbiturates: The Oblivion Express by Jim Parker; ISBN: 0892301848; http://www.amazon.com/exec/obidos/ASIN/0892301848/icongroupinterna
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Barbiturates: Their Use, Misuse and Abuse by Donald R. Wesson, David E. Smith; ISBN: 0877053146; http://www.amazon.com/exec/obidos/ASIN/0877053146/icongroupinterna
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The effect of barbiturates on the myocardium and its reversibility by Rolf Krebs; ISBN: 3437105582; http://www.amazon.com/exec/obidos/ASIN/3437105582/icongroupinterna
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Tranquilizer, Barbiturate, and Downer Drug Dangers (Drug Dangers) by Michelle M. Houle; ISBN: 0766013200; http://www.amazon.com/exec/obidos/ASIN/0766013200/icongroupinterna
Chapters on Barbiturates In order to find chapters that specifically relate to barbiturates, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and barbiturates using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “barbiturates” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on barbiturates: •
Chemical Dependence Source: in Scully, C. and Cawson, R.A. Medical Problems in Dentistry. 4th ed. Woburn, MA: Butterworth-Heinemann. 1998. p. 488-505. Contact: Available from Butterworth-Heinemann. 225 Wildwood Avenue, Woburn, MA 01801-2041. (800) 366-2665 or (781) 904-2500. Fax (800) 446-6520 or (781) 933-6333. E-mail:
[email protected]. Website: www.bh.com. PRICE: $110.00. ISBN: 0723610568. Summary: Chemical dependence (substance or drug abuse) is a growing problem worldwide. Abuse of a drug is defined as self-administration in a manner that deviates from the cultural norm and is harmful. Addiction is defined as the continued use of a specific psychoactive substance despite physical, psychological, or social harm. This chapter on chemical dependence is from a text that covers the general medical and surgical conditions relevant to the oral health care sciences. Topics include aspects of chemical dependence, the consumption of alcohol, fetal alcohol syndrome, alcohol withdrawal, nicotine and tobacco, benzodiazepines, barbiturates, opioids (narcotics), amphetamines, cocaine, psychedelic drugs (cannabis, LSD, PCP, ketamine), anesthetic abuse, and anabolic steroids. For each condition, the authors discuss general aspects, diagnosis and management issues, dental aspects, and patient care strategies. The chapter includes a summary of the points covered. One appendix lists street names and other terms for drugs of abuse. 4 tables. 38 references.
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CHAPTER 7. PERIODICALS AND NEWS ON BARBITURATES Overview In this chapter, we suggest a number of news sources and present various periodicals that cover barbiturates.
News Services and Press Releases One of the simplest ways of tracking press releases on barbiturates 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 “barbiturates” (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 barbiturates. 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 “barbiturates” (or synonyms). The following was recently listed in this archive for barbiturates: •
OraSure screening assay for barbiturates, methadone approved Source: Reuters Industry Breifing Date: January 26, 2001
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Taro adds to non-sedating barbiturates patent portfolio Source: Reuters Industry Breifing Date: August 01, 2000
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Atypical Symptoms In Migraine Patients May Signal Barbiturate Withdrawal Source: Reuters Medical News Date: March 19, 1998 The NIH
Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. 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 “barbiturates” (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 “barbiturates” (or synonyms). If you know the name of a company that is relevant to barbiturates, 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 “barbiturates” (or synonyms).
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Academic Periodicals covering Barbiturates Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to barbiturates. In addition to these sources, you can search for articles covering barbiturates that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”
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CHAPTER 8. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.
U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for barbiturates. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a nonprofit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI® Advice for the Patient® can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with barbiturates. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The
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following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to barbiturates: Barbiturates, Aspirin, and Codeine •
Systemic - U.S. Brands: Ascomp with Codeine No.3; Butalbital Compound with Codeine; Butinal with Codeine No.3; Fiorinal with Codeine No.3; Idenal with Codeine; Isollyl with Codeine http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202104.html
Belladonna Alkaloids and Barbiturates •
Systemic - U.S. Brands: Antrocol; Barbidonna; Barbidonna No. 2; Barophen; Bellalphen; Butibel; Donnamor; Donnapine; Donnatal; Donnatal Extentabs; Donnatal No. 2; Donphen; Hyosophen; Kinesed; Malatal; Relaxadon; Spaslin; Spasmolin; Spasmophen; Spasquid; Susano http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202082.html
Butalbital and Acetaminophen •
Systemic - U.S. Brands: Amaphen; Anolor-300; Anoquan; Arcet; Bancap; Bucet; Butace; Conten; Dolmar; Endolor; Esgic; Esgic-Plus; Ezol; Femcet; Fioricet; Isocet; Medigesic; Pacaps; Pharmagesic; Phrenilin; Phrenilin Forte; Repan; Sedapap; Tencet; Tencon; Triad; Triaprin; Two-Dyne http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202102.html
Butalbital and Aspirin •
Systemic - U.S. Brands: Axotal; Butalgen; Fiorgen; Fiorinal; Fiormor; Fortabs; Isobutal; Isobutyl; Isolin; Isollyl; Laniroif; Lanorinal; Marnal; Vibutal http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202103.html
Ergotamine, Belladonna Alkaloids, and Phenobarbital •
Systemic - U.S. Brands: Bellergal-S http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202217.html
Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.
Mosby’s Drug Consult™ Mosby’s Drug Consult™ database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/.
Researching Medications
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PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.
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APPENDICES
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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.
NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute10: •
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/
10
These publications are typically written by one or more of the various NIH Institutes.
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•
National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm
•
National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
•
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
•
National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
•
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
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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.11 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:12 •
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
11
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). 12 See http://www.nlm.nih.gov/databases/databases.html.
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Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html
•
Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html
The NLM Gateway13 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.14 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “barbiturates” (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 45918 153 647 12 204 46934
HSTAT15 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.16 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.17 Simply search by “barbiturates” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
13
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
14
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). 15 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 16 17
The HSTAT URL is http://hstat.nlm.nih.gov/.
Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.
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Coffee Break: Tutorials for Biologists18 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.19 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.20 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/.
18 Adapted 19
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. 20 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 barbiturates 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 barbiturates. 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 barbiturates. 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 “barbiturates”:
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•
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Other guides Club Drugs http://www.nlm.nih.gov/medlineplus/clubdrugs.html Marijuana Abuse http://www.nlm.nih.gov/medlineplus/marijuanaabuse.html Prescription Drug Abuse http://www.nlm.nih.gov/medlineplus/prescriptiondrugabuse.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 Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on barbiturates. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •
Drugs and Porphyria Source: Houston, TX: American Porphyria Foundation. 199x. 6 p. Contact: Available from American Porphyria Foundation. P.O. Box 22712, Houston, TX 77227-2712. (713) 266-9617. Fax (713) 871-1788. Website: www.enterprise.net/apf/. PRICE: Single copy free to members only ($30.00 membership fee); online version available for $5.00 access fee. Summary: This brochure for health professionals and people with porphyria addresses the use of drugs to treat the disease. Some drugs, such as barbiturates, make porphyria worse by increasing the synthesis of heme and cytochrome P450 in the liver. However, even a drug that does not have these effects sometimes causes porphyria to worsen through other mechanisms that are not well understood. Various laboratory studies can help determine which drugs cause increases in the synthesis of heme and cytochrome P450 in the liver. The brochure also discusses the problem of a porphyria attack after exposure to a safe drug and explains why a patient may not experience an attack after exposure to a harmful drug. A list of drugs considered safe and unsafe for people with acute porphyrias is provided. 1 table.
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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 barbiturates. 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/
•
WebMD®Health: http://my.webmd.com/health_topics
Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to barbiturates. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with barbiturates. 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 barbiturates. 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
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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 “barbiturates” (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 “barbiturates”. 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 “barbiturates” (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 “barbiturates” (or a synonym) into the search box, and click “Submit Query.”
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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.
Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.21
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
21
Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.
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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)22: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
•
Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
•
Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
•
California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html
•
California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html
•
California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html
•
California: Gateway Health Library (Sutter Gould Medical Foundation)
•
California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/
•
California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
•
California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
•
California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/
•
California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/
•
California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/
•
California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html
•
California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/
•
Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/
•
Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/
•
Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/
22
Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
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•
Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml
•
Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm
•
Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
•
Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
•
Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
•
Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
•
Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
•
Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
•
Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
•
Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
•
Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
•
Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
•
Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
•
Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
•
Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
•
Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm
•
Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
•
Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
•
Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10
•
Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/
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Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html
•
Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
•
Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp
•
Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
•
Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html
•
Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
•
Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp
•
Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/
•
Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html
•
Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/
•
Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
•
Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
•
Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
•
Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm
•
Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330
•
Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
•
National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
•
National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/
•
National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
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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
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New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/
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New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html
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New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/
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Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm
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Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp
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Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/
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Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/
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Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml
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Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html
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Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html
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Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml
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Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp
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Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm
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Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/
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South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp
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Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/
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Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/
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Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72
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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •
ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html
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MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
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Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
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Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html
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On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/
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Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp
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Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm
Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on barbiturates: •
Basic Guidelines for Barbiturates Barbiturate intoxication Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000951.htm Barbiturates overdose Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002573.htm
•
Signs & Symptoms for Barbiturates Blisters Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003939.htm Coma Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003202.htm Confusion Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003205.htm
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Emesis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm Excitement Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003212.htm Forgetfulness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003257.htm Headache Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003024.htm Low blood pressure Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003083.htm Memory loss Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003257.htm Respiration slowed or stopped Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003069.htm Weak pulse Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003078.htm •
Diagnostics and Tests for Barbiturates Blood chemistries Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003468.htm Gastric lavage Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003882.htm Pulse Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003399.htm
•
Background Topics for Barbiturates Breathing problems Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000007.htm Chronic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002312.htm Respiratory Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002290.htm
Online Glossaries 93
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
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Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
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Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
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BARBITURATES DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 2-Propanol: An isomer of 1-propanol. It is a colorless liquid having disinfectant properties. It is used in the manufacture of acetone and its derivatives and as a solvent. Topically, it is used as an antiseptic. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] 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] Acidosis: A pathologic condition resulting from accumulation of acid or depletion of the alkaline reserve (bicarbonate content) in the blood and body tissues, and characterized by an increase in hydrogen ion concentration. [EU] Acrylonitrile: A highly poisonous compound used widely in the manufacture of plastics, adhesives and synthetic rubber. [NIH] Acyl: Chemical signal used by bacteria to communicate. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [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] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids,
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androgens, and glucocorticoids. [NIH] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]
Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the 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] Ageing: A physiological or morphological change in the life of an organism or its parts, generally irreversible and typically associated with a decline in growth and reproductive vigor. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Akathisia: 1. A condition of motor restlessness in which there is a feeling of muscular quivering, an urge to move about constantly, and an inability to sit still, a common extrapyramidal side effect of neuroleptic drugs. 2. An inability to sit down because of intense anxiety at the thought of doing so. [EU] Alanine: A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases immunity, and provides energy for muscle tissue, brain, and the central nervous system. [NIH] Alexia: The inability to recognize or comprehend written or printed words. [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] Alkylating Agents: Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases. [NIH]
Alkylation: The covalent bonding of an alkyl group to an organic compound. It can occur by a simple addition reaction or by substitution of another functional group. [NIH]
Dictionary 97
Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allylamine: Possesses an unusual and selective cytotoxicity for vascular smooth muscle cells in dogs and rats. Useful for experiments dealing with arterial injury, myocardial fibrosis or cardiac decompensation. [NIH] Alpha-1: A protein with the property of inactivating proteolytic enzymes such as leucocyte collagenase and elastase. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98. [NIH] Amination: The creation of an amine. It can be produced by the addition of an amino group to an organic compound or reduction of a nitro group. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Aminophylline: A drug combination that contains theophylline and ethylenediamine. It is more soluble in water than theophylline but has similar pharmacologic actions. It's most common use is in bronchial asthma, but it has been investigated for several other applications. [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] Amnesia: Lack or loss of memory; inability to remember past experiences. [EU] Amnestic: Nominal aphasia; a difficulty in finding the right name for an object. [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] Anabolic: Relating to, characterized by, or promoting anabolism. [EU]
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Anabolic Steroids: Chemical derivatives of testosterone that are used for anabolic promotion of growth and repair of body tissues and the development of male sexual characteristics. [NIH] Anaerobic: 1. Lacking molecular oxygen. 2. Growing, living, or occurring in the absence of molecular oxygen; pertaining to an anaerobe. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Analeptic: A drug which acts as a restorative, such as caffeine, amphetamine, pentylenetetrazol, etc. [EU] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Analytes: A component of a test sample the presence of which has to be demonstrated. The term "analyte" includes where appropriate formed from the analyte during the analyses. [NIH]
Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] 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] Aneurysm: A sac formed by the dilatation of the wall of an artery, a vein, or the heart. [NIH] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Anisotropy: A physical property showing different values in relation to the direction in or along which the measurement is made. The physical property may be with regard to thermal or electric conductivity or light refraction. In crystallography, it describes crystals whose index of refraction varies with the direction of the incident light. It is also called acolotropy and colotropy. The opposite of anisotropy is isotropy wherein the same values characterize the object when measured along axes in all directions. [NIH] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH]
Dictionary 99
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] Anti-Anxiety Agents: Agents that alleviate anxiety, tension, and neurotic symptoms, promote sedation, and have a calming effect without affecting clarity of consciousness or neurologic conditions. Some are also effective as anticonvulsants, muscle relaxants, or anesthesia adjuvants. Adrenergic beta-antagonists are commonly used in the symptomatic treatment of anxiety but are not included here. [NIH] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]
Antibiotic Prophylaxis: Use of antibiotics before, during, or after a diagnostic, therapeutic, or surgical procedure to prevent infectious complications. [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] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antidepressive Agents: Mood-stimulating drugs used primarily in the treatment of affective disorders and related conditions. Several monoamine oxidase inhibitors are useful as antidepressants apparently as a long-term consequence of their modulation of catecholamine levels. The tricyclic compounds useful as antidepressive agents also appear to act through brain catecholamine systems. A third group (antidepressive agents, secondgeneration) is a diverse group of drugs including some that act specifically on serotonergic systems. [NIH] Antidote: A remedy for counteracting a poison. [EU] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [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] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU]
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Antipsychotic: Effective in the treatment of psychosis. Antipsychotic drugs (called also neuroleptic drugs and major tranquilizers) are a chemically diverse (including phenothiazines, thioxanthenes, butyrophenones, dibenzoxazepines, dibenzodiazepines, and diphenylbutylpiperidines) but pharmacologically similar class of drugs used to treat schizophrenic, paranoid, schizoaffective, and other psychotic disorders; acute delirium and dementia, and manic episodes (during induction of lithium therapy); to control the movement disorders associated with Huntington's chorea, Gilles de la Tourette's syndrome, and ballismus; and to treat intractable hiccups and severe nausea and vomiting. Antipsychotic agents bind to dopamine, histamine, muscarinic cholinergic, a-adrenergic, and serotonin receptors. Blockade of dopaminergic transmission in various areas is thought to be responsible for their major effects : antipsychotic action by blockade in the mesolimbic and mesocortical areas; extrapyramidal side effects (dystonia, akathisia, parkinsonism, and tardive dyskinesia) by blockade in the basal ganglia; and antiemetic effects by blockade in the chemoreceptor trigger zone of the medulla. Sedation and autonomic side effects (orthostatic hypotension, blurred vision, dry mouth, nasal congestion and constipation) are caused by blockade of histamine, cholinergic, and adrenergic receptors. [EU] Antipsychotic Agents: Agents that control agitated psychotic behavior, alleviate acute psychotic states, reduce psychotic symptoms, and exert a quieting effect. They are used in schizophrenia, senile dementia, transient psychosis following surgery or myocardial infarction, etc. These drugs are often referred to as neuroleptics alluding to the tendency to produce neurological side effects, but not all antipsychotics are likely to produce such effects. Many of these drugs may also be effective against nausea, emesis, and pruritus. [NIH] Antiseptic: A substance that inhibits the growth and development of microorganisms without necessarily killing them. [EU] Antiserum: The blood serum obtained from an animal after it has been immunized with a particular antigen. It will contain antibodies which are specific for that antigen as well as antibodies specific for any other antigen with which the animal has previously been immunized. [NIH] Antispasmodic: An agent that relieves spasm. [EU] Antitussive: An agent that relieves or prevents cough. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Antiviral Agents: Agents used in the prophylaxis or therapy of virus diseases. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Anxiety Disorders: Disorders in which anxiety (persistent feelings of apprehension, tension, or uneasiness) is the predominant disturbance. [NIH] Anxiolytic: An anxiolytic or antianxiety agent. [EU] Aqueous: Having to do with water. [NIH] Aromatic: Having a spicy odour. [EU] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Aspartate: A synthetic amino acid. [NIH] Aspartic: The naturally occurring substance is L-aspartic acid. One of the acidic-amino-acids is obtained by the hydrolysis of proteins. [NIH]
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Aspartic Acid: One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter. [NIH] Asphyxia: A pathological condition caused by lack of oxygen, manifested in impending or actual cessation of life. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Atmospheric Pressure: The pressure at any point in an atmosphere due solely to the weight of the atmospheric gases above the point concerned. [NIH] Atropine: A toxic alkaloid, originally from Atropa belladonna, but found in other plants, mainly Solanaceae. [NIH] Auditory: Pertaining to the sense of hearing. [EU] Auditory Cortex: Area of the temporal lobe concerned with hearing. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the central nervous system, especially the hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [NIH] 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 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] 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] Barbital: A long-acting barbiturate that depresses most metabolic processes at high doses. It is used as a hypnotic and sedative and may induce dependence. Barbital is also used in veterinary practice for central nervous system depression. [NIH] Barbiturate: A drug with sedative and hypnotic effects. Barbiturates have been used as sedatives and anesthetics, and they have been used to treat the convulsions associated with epilepsy. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH]
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Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]
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] Benzoic Acid: A fungistatic compound that is widely used as a food preservative. It is conjugated to glycine in the liver and excreted as hippuric acid. [NIH] Bicuculline: Isoquinoline alkaloid from Dicentra cucullaria and other plants that is a competitive antagonist at GABA-A receptors and thus causes convulsions. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Bioassay: Determination of the relative effective strength of a substance (as a vitamin, hormone, or drug) by comparing its effect on a test organism with that of a standard preparation. [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] Bipolar Disorder: A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence. [NIH] Bladder: The organ that stores urine. [NIH] Bloating: Fullness or swelling in the abdomen that often occurs after meals. [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. 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]
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Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood-Brain Barrier: Specialized non-fenestrated tightly-joined endothelial cells (tight junctions) that form a transport barrier for certain substances between the cerebral capillaries and the brain tissue. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Brain Infarction: The formation of an area of necrosis in the brain, including the cerebral hemispheres (cerebral infarction), thalami, basal ganglia, brain stem (brain stem infarctions), or cerebellum secondary to an insufficiency of arterial or venous blood flow. [NIH] Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Brain Stem Infarctions: Infarctions that occur in the brain stem which is comprised of the midbrain, pons, and medulla. There are several named syndromes characterized by their distinctive clinical manifestations and specific sites of ischemic injury. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]
Breakdown: A physical, metal, or nervous collapse. [NIH] Bromine: A halogen with the atomic symbol Br, atomic number 36, and atomic weight 79.904. It is a volatile reddish-brown liquid that gives off suffocating vapors, is corrosive to the skin, and may cause severe gastroenteritis if ingested. [NIH] Bromine Compounds: Inorganic compounds that contain bromine as an integral part of the molecule. [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bulimia: Episodic binge eating. The episodes may be associated with the fear of not being able to stop eating, depressed mood, or self-deprecating thoughts (binge-eating disorder) and may frequently be terminated by self-induced vomiting (bulimia nervosa). [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] Buspirone: An anxiolytic agent and a serotonin receptor agonist belonging to the azaspirodecanedione class of compounds. Its structure is unrelated to those of the benzodiazepines, but it has an efficacy comparable to diazepam. [NIH] Butadienes: Four carbon unsaturated hydrocarbons containing two double bonds. [NIH] Butyric Acid: A four carbon acid, CH3CH2CH2COOH, with an unpleasant odor that occurs
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in butter and animal fat as the glycerol ester. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium Carbonate: Carbonic acid calcium salt (CaCO3). An odorless, tasteless powder or crystal that occurs in nature. It is used therapeutically as a phosphate buffer in hemodialysis patients and as a calcium supplement. [NIH] Calcium Hydroxide: Ca(OH)2. A white powder that has many therapeutic uses. Because of its ability to stimulate mineralization, it is found in many dental formulations. [NIH] Calcium Sulfate: It exists in an anhydrous form and in various states of hydration: the hemihydrate is plaster of Paris, the dihydrate is gypsum. It is used in building materials, as a desiccant, in dentistry as an impression material, cast, or die, and in medicine for immobilizing casts and as a tablet excipient. [NIH] Calculi: An abnormal concretion occurring mostly in the urinary and biliary tracts, usually composed of mineral salts. Also called stones. [NIH] Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels. [NIH] Cannabidiol: Compound isolated from Cannabis sativa extract. [NIH] Cannabinoids: Compounds extracted from Cannabis sativa L. and metabolites having the cannabinoid structure. The most active constituents are tetrahydrocannabinol, cannabinol, and cannabidiol. [NIH] Cannabinol: A physiologically inactive constituent of Cannabis sativa L. [NIH] Cannabis: The hemp plant Cannabis sativa. Products prepared from the dried flowering tops of the plant include marijuana, hashish, bhang, and ganja. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Carbohydrates: The largest class of organic compounds, including starches, glycogens, cellulose, gums, and simple sugars. Carbohydrates are composed of carbon, hydrogen, and oxygen in a ratio of Cn(H2O)n. [NIH] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carboxy: Cannabinoid. [NIH] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinogenic: Producing carcinoma. [EU] Cardiac: Having to do with the heart. [NIH] Cardiac arrest: A sudden stop of heart function. [NIH] Cardiorespiratory: Relating to the heart and lungs and their function. [EU]
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Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Cardiovascular System: The heart and the blood vessels by which blood is pumped and circulated through the body. [NIH] 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] Catheterization: Use or insertion of a tubular device into a duct, blood vessel, hollow organ, or body cavity for injecting or withdrawing fluids for diagnostic or therapeutic purposes. It differs from intubation in that the tube here is used to restore or maintain patency in obstructions. [NIH] Cathode: An electrode, usually an incandescent filament of tungsten, which emits electrons in an X-ray tube. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Communication: Any of several ways in which living cells of an organism communicate with one another, whether by direct contact between cells or by means of chemical signals carried by neurotransmitter substances, hormones, and cyclic AMP. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Division: The fission of a cell. [NIH] Cell Extracts: Preparations of cell constituents or subcellular materials, isolates, or substances. [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] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Cerebellar: Pertaining to the cerebellum. [EU]
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Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral hemispheres: The two halves of the cerebrum, the part of the brain that controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. The right hemisphere controls muscle movement on the left side of the body, and the left hemisphere controls muscle movement on the right side of the body. [NIH] Cerebral Infarction: The formation of an area of necrosis in the cerebrum caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., infarction, anterior cerebral artery), and etiology (e.g., embolic infarction). [NIH]
Cerebral Palsy: Refers to a motor disability caused by a brain dysfunction. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Chemoreceptor: A receptor adapted for excitation by chemical substances, e.g., olfactory and gustatory receptors, or a sense organ, as the carotid body or the aortic (supracardial) bodies, which is sensitive to chemical changes in the blood stream, especially reduced oxygen content, and reflexly increases both respiration and blood pressure. [EU] Chemotherapy: Treatment with anticancer drugs. [NIH] Chlordiazepoxide: An anxiolytic benzodiazepine derivative with anticonvulsant, sedative, and amnesic properties. It has also been used in the symptomatic treatment of alcohol withdrawl. [NIH] Chlorine: A greenish-yellow, diatomic gas that is a member of the halogen family of elements. It has the atomic symbol Cl, atomic number 17, and atomic weight 70.906. It is a powerful irritant that can cause fatal pulmonary edema. Chlorine is used in manufacturing, as a reagent in synthetic chemistry, for water purification, and in the production of chlorinated lime, which is used in fabric bleaching. [NIH] Choline: A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Cholinergic Agents: Any drug used for its actions on cholinergic systems. Included here are agonists and antagonists, drugs that affect the life cycle of acetylcholine, and drugs that affect the survival of cholinergic neurons. The term cholinergic agents is sometimes still used in the narrower sense of muscarinic agonists, although most modern texts discourage that usage. [NIH] Chorea: Involuntary, forcible, rapid, jerky movements that may be subtle or become confluent, markedly altering normal patterns of movement. Hypotonia and pendular reflexes are often associated. Conditions which feature recurrent or persistent episodes of chorea as a primary manifestation of disease are referred to as choreatic disorders. Chorea is also a frequent manifestation of basal ganglia diseases. [NIH] Choreatic Disorders: Acquired and hereditary conditions which feature chorea as a primary manifestation of the disease process. [NIH]
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Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Cinnarizine: A piperazine derivative with histamine H1-receptor and calcium-channel blocking activity and considerable antiemetic properties. [NIH] Circulatory system: The system that contains the heart and the blood vessels and moves blood throughout the body. This system helps tissues get enough oxygen and nutrients, and it helps them get rid of waste products. The lymph system, which connects with the blood system, is often considered part of the circulatory system. [NIH] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [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] Coal: A natural fuel formed by partial decomposition of vegetable matter under certain environmental conditions. [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] Cochlea: The part of the internal ear that is concerned with hearing. It forms the anterior part of the labyrinth, is conical, and is placed almost horizontally anterior to the vestibule. [NIH]
Cochlear: Of or pertaining to the cochlea. [EU] Cochlear Nerve: The cochlear part of the 8th cranial nerve (vestibulocochlear nerve). The cochlear nerve fibers originate from neurons of the spiral ganglion and project peripherally to cochlear hair cells and centrally to the cochlear nuclei (cochlear nucleus) of the brain stem. They mediate the sense of hearing. [NIH] Cochlear Nucleus: The brain stem nucleus that receives the central input from the cochlear nerve. The cochlear nucleus is located lateral and dorsolateral to the inferior cerebellar peduncles and is functionally divided into dorsal and ventral parts. It is tonotopically organized, performs the first stage of central auditory processing, and projects (directly or indirectly) to higher auditory areas including the superior olivary nuclei, the medial geniculi, the inferior colliculi, and the auditory cortex. [NIH] Codeine: An opioid analgesic related to morphine but with less potent analgesic properties and mild sedative effects. It also acts centrally to suppress cough. [NIH]
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Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Comatose: Pertaining to or affected with coma. [EU] 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
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theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Conjugated: Acting or operating as if joined; simultaneous. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constriction: The act of constricting. [NIH] Constriction, Pathologic: The condition of an anatomical structure's being constricted beyond normal dimensions. [NIH] Consumption: Pulmonary tuberculosis. [NIH] 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 heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corpus: The body of the uterus. [NIH] Corpus Luteum: The yellow glandular mass formed in the ovary by an ovarian follicle that has ruptured and discharged its ovum. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH]
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Craniotomy: An operation in which an opening is made in the skull. [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] Cutaneous: Having to do with the skin. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. [NIH]
Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Deamination: The removal of an amino group (NH2) from a chemical compound. [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]
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Delusions: A false belief regarding the self or persons or objects outside the self that persists despite the facts, and is not considered tenable by one's associates. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Care: The total of dental diagnostic, preventive, and restorative services provided to meet the needs of a patient (from Illustrated Dictionary of Dentistry, 1982). [NIH] Deoxyuridine: 2'-Deoxyuridine. An antimetabolite that is converted to deoxyuridine triphosphate during DNA synthesis. Laboratory suppression of deoxyuridine is used to diagnose megaloblastic anemias due to vitamin B12 and folate deficiencies. [NIH] Depersonalization: Alteration in the perception of the self so that the usual sense of one's own reality is lost, manifested in a sense of unreality or self-estrangement, in changes of body image, or in a feeling that one does not control his own actions and speech; seen in depersonalization disorder, schizophrenic disorders, and schizotypal personality disorder. Some do not draw a distinction between depersonalization and derealization, using depersonalization to include both. [EU] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Derealization: Is characterized by the loss of the sense of reality concerning one's surroundings. [NIH] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] Detoxification: Treatment designed to free an addict from his drug habit. [EU] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Dexmedetomidine: A selective inhibitor of receptors, adrenergic alpha-2 that has analgesic and sedative properties. Medetomidine is the other racemic form. [NIH] Dextroamphetamine: The d-form of amphetamine. It is a central nervous system stimulant and a sympathomimetic. It has also been used in the treatment of narcolepsy and of attention deficit disorders and hyperactivity in children. Dextroamphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulating release of monamines, and inhibiting monoamine oxidase. It is also a drug of abuse and a psychotomimetic. [NIH] Dextromethorphan: The d-isomer of the codeine analog of levorphanol. Dextromethorphan shows high affinity binding to several regions of the brain, including the medullary cough center. This compound is a NMDA receptor antagonist (receptors, N-methyl-D-aspartate) and acts as a non-competitive channel blocker. It is used widely as an antitussive agent, and is also used to study the involvement of glutamate receptors in neurotoxicity. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH]
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Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dilatation: The act of dilating. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [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] Diuretic: A drug that increases the production of urine. [NIH] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Dorsum: A plate of bone which forms the posterior boundary of the sella turcica. [NIH] Dose-dependent: Refers to the effects of treatment with a drug. If the effects change when the dose of the drug is changed, the effects are said to be dose dependent. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH]
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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] Duct: A tube through which body fluids pass. [NIH] Duodenum: The first part of the small intestine. [NIH] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dyskinesia: Impairment of the power of voluntary movement, resulting in fragmentary or incomplete movements. [EU] Dyslexia: Partial alexia in which letters but not words may be read, or in which words may be read but not understood. [NIH] Dyspnea: Difficult or labored breathing. [NIH] Dystonia: Disordered tonicity of muscle. [EU] Eating Disorders: A group of disorders characterized by physiological and psychological disturbances in appetite or food intake. [NIH] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Effector cell: A cell that performs a specific function in response to a stimulus; usually used to describe cells in the immune system. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] 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] Electrolysis: Destruction by passage of a galvanic electric current, as in disintegration of a chemical compound in solution. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU] Electroplating: Coating with a metal or alloy by electrolysis. [NIH]
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Embolus: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Emesis: Vomiting; an act of vomiting. Also used as a word termination, as in haematemesis. [EU]
Emetic: An agent that causes vomiting. [EU] Empyema: Presence of pus in a hollow organ or body cavity. [NIH] Endocrine Glands: Ductless glands that secrete substances which are released directly into the circulation and which influence metabolism and other body functions. [NIH] Endopeptidases: A subclass of peptide hydrolases. They are classified primarily by their catalytic mechanism. Specificity is used only for identification of individual enzymes. They comprise the serine endopeptidases, EC 3.4.21; cysteine endopeptidases, EC 3.4.22; aspartic endopeptidases, EC 3.4.23, metalloendopeptidases, EC 3.4.24; and a group of enzymes yet to be assigned to any of the above sub-classes, EC 3.4.99. EC 3.4.-. [NIH] Endoscopic: A technique where a lateral-view endoscope is passed orally to the duodenum for visualization of the ampulla of Vater. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endotoxins: Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Enflurane: An extremely stable inhalation anesthetic that allows rapid adjustments of anesthesia depth with little change in pulse or respiratory rate. [NIH] Enteric Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [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] Enzyme Multiplied Immunoassay Technique: An immunoenzyme test that uses antibodies to detect the presence of drugs and other substances in the urine and blood. The test uses antibodies that react only with the particular drug for which the sample is being tested. In the test mixture the antibodies attach themselves to the drug if it is present in the sample. It is not designed to measure amounts of the drug present, only its presence or absence. It is commonly seen in the literature as EMIT (d.a.u.) wherein the d.a.u. means "drugs of abuse in urine". Though launched in 1973 for the study of antiepilepsy drugs, it is now used predominantly, but not exclusively, for the detection of drugs of abuse in the urine. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH]
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Epithelial Cells: Cells that line the inner and outer surfaces of the body. [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] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]
Esterification: The process of converting an acid into an alkyl or aryl derivative. Most frequently the process consists of the reaction of an acid with an alcohol in the presence of a trace of mineral acid as catalyst or the reaction of an acyl chloride with an alcohol. Esterification can also be accomplished by enzymatic processes. [NIH] 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] Ether: One of a class of organic compounds in which any two organic radicals are attached directly to a single oxygen atom. [NIH] Etomidate: Imidazole derivative anesthetic and hypnotic with little effect on blood gases, ventilation, or the cardiovascular system. It has been proposed as an induction anesthetic. [NIH]
Euthanasia: The act or practice of putting to death people or animals suffering from incurable conditions or diseases. [NIH] Excipient: Any more or less inert substance added to a prescription in order to confer a suitable consistency or form to the drug; a vehicle. [EU] 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] 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] Excitatory Amino Acids: Endogenous amino acids released by neurons as excitatory neurotransmitters. Glutamic acid is the most common excitatory neurotransmitter in the brain. Aspartic acid has been regarded as an excitatory transmitter for many years, but the extent of its role as a transmitter is unclear. [NIH] Excitotoxicity: Excessive exposure to glutamate or related compounds can kill brain neurons, presumably by overstimulating them. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and
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laminin). [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extraction: The process or act of pulling or drawing out. [EU] Extrapyramidal: Outside of the pyramidal tracts. [EU] 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] Febrile: Pertaining to or characterized by fever. [EU] Fentanyl: A narcotic opioid drug that is used in the treatment of pain. [NIH] Fertilizers: Substances or mixtures that are added to the soil to supply nutrients or to make available nutrients already present in the soil, in order to increase plant growth and productivity. [NIH] Fetal Alcohol Syndrome: A disorder occurring in children born to alcoholic women who continue to drink heavily during pregnancy. Common abnormalities are growth deficiency (prenatal and postnatal), altered morphogenesis, mental deficiency, and characteristic facies - small eyes and flattened nasal bridge. Fine motor dysfunction and tremulousness are observed in the newborn. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU] Flame Retardants: Materials applied to fabrics, bedding, furniture, plastics, etc. to retard their burning; many may leach out and cause allergies or other harm. [NIH] Flatus: Gas passed through the rectum. [NIH] Flumazenil: A potent benzodiazepine receptor antagonist. Since it reverses the sedative and other actions of benzodiazepines, it has been suggested as an antidote to benzodiazepine overdoses. [NIH] Flunarizine: Flunarizine is a selective calcium entry blocker with calmodulin binding properties and histamine H1 blocking activity. It is effective in the prophylaxis of migraine, occlusive peripheral vascular disease, vertigo of central and peripheral origin, and as an adjuvant in the therapy of epilepsy. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluorescence Polarization: Measurement of the polarization of fluorescent light from solutions or microscopic specimens. It is used to provide information concerning molecular size, shape, and conformation, molecular anisotropy, electronic energy transfer, molecular interaction, including dye and coenzyme binding, and the antigen-antibody reaction. [NIH] Fluorescence Polarization Immunoassay: Fluoroimmunoassay where detection of the hapten-antibody reaction is based on measurement of the increased polarization of fluorescence-labeled hapten when it is combined with antibody. The assay is very useful for the measurement of small haptenic antigens such as drugs at low concentrations. [NIH] Fluorouracil: A pyrimidine analog that acts as an antineoplastic antimetabolite and also has immunosuppressant. It interferes with DNA synthesis by blocking the thymidylate
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synthetase conversion of deoxyuridylic acid to thymidylic acid. [NIH] Folate: A B-complex vitamin that is being studied as a cancer prevention agent. Also called folic acid. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Free Radical Scavengers: Substances that influence the course of a chemical reaction by ready combination with free radicals. Among other effects, this combining activity protects pancreatic islets against damage by cytokines and prevents myocardial and pulmonary perfusion injuries. [NIH] Fungistatic: Inhibiting the growth of fungi. [EU] Furosemide: A sulfamyl saluretic and diuretic. It has a fast onset and short duration of action and is used in edema and chronic renal insufficiency. [NIH] Gallic Acid: A colorless or slightly yellow crystalline compound obtained from nutgalls. It is used in photography, pharmaceuticals, and as an analytical reagent. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gap Junctions: Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of connexins, the family of proteins which form the junctions. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gasoline: Volative flammable fuel (liquid hydrocarbons) derived from crude petroleum by processes such as distillation reforming, polymerization, etc. [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Acid: Hydrochloric acid present in gastric juice. [NIH] Gastroenteritis: An acute inflammation of the lining of the stomach and intestines, characterized by anorexia, nausea, diarrhoea, abdominal pain, and weakness, which has various causes, including food poisoning due to infection with such organisms as Escherichia coli, Staphylococcus aureus, and Salmonella species; consumption of irritating food or drink; or psychological factors such as anger, stress, and fear. Called also enterogastritis. [EU] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]
Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH]
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Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]
Glomerular Filtration Rate: The volume of water filtered out of plasma through glomerular capillary walls into Bowman's capsules per unit of time. It is considered to be equivalent to inulin clearance. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [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] Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]
Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [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] Glycogen: A sugar stored in the liver and muscles. It releases glucose into the blood when cells need it for energy. Glycogen is the chief source of stored fuel in the body. [NIH] Glycols: A generic grouping for dihydric alcohols with the hydroxy groups (-OH) located on different carbon atoms. They are viscous liquids with high boiling points for their molecular weights. [NIH] Glycosidic: Formed by elimination of water between the anomeric hydroxyl of one sugar and a hydroxyl of another sugar molecule. [NIH] Gout: Hereditary metabolic disorder characterized by recurrent acute arthritis, hyperuricemia and deposition of sodium urate in and around the joints, sometimes with formation of uric acid calculi. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU]
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Granule: A small pill made from sucrose. [EU] Granulosa Cells: Cells of the membrana granulosa lining the vesicular ovarian follicle which become luteal cells after ovulation. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Guanidine: A strong organic base existing primarily as guanidium ions at physiological pH. It is found in the urine as a normal product of protein metabolism. It is also used in laboratory research as a protein denaturant. (From Martindale, the Extra Pharmacopoeia, 30th ed and Merck Index, 12th ed) It is also used in the treatment of myasthenia and as a fluorescent probe in HPLC. [NIH] Habituation: Decline in response of an organism to environmental or other stimuli with repeated or maintained exposure. [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] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [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] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular
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weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] Hepatic: Refers to the liver. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Herbicide: A chemical that kills plants. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] 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]
Hexobarbital: A barbiturate that is effective as a hypnotic and sedative. [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hydration: Combining with water. [NIH] Hydrobromic Acid: Hydrobromic acid (HBr). A solution of hydrogen bromide gas in water. [NIH]
Hydrocephalus: Excessive accumulation of cerebrospinal fluid within the cranium which may be associated with dilation of cerebral ventricles, intracranial hypertension; headache; lethargy; urinary incontinence; and ataxia (and in infants macrocephaly). This condition may be caused by obstruction of cerebrospinal fluid pathways due to neurologic abnormalities, intracranial hemorrhages; central nervous system infections; brain neoplasms; craniocerebral trauma; and other conditions. Impaired resorption of cerebrospinal fluid from the arachnoid villi results in a communicating form of hydrocephalus. Hydrocephalus ex-vacuo refers to ventricular dilation that occurs as a result of brain substance loss from cerebral infarction and other conditions. [NIH] Hydrochloric Acid: A strong corrosive acid that is commonly used as a laboratory reagent. It is formed by dissolving hydrogen chloride in water. Gastric acid is the hydrochloric acid component of gastric juice. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless,
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odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxides: Inorganic compounds that contain the OH- group. [NIH] Hydroxyl Radical: The univalent radical OH that is present in hydroxides, alcohols, phenols, glycols. [NIH] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hyperkalaemia: Pathology: an abnormally high concentration of potassium in the blood. [EU]
Hyperkinesia: Abnormally increased motor function or activity; hyperactivity. [EU] Hypersecretion: Excessive secretion. [EU] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hyperuricemia: A buildup of uric acid (a byproduct of metabolism) in the blood; a side effect of some anticancer drugs. [NIH] Hyperventilation: A pulmonary ventilation rate faster than is metabolically necessary for the exchange of gases. It is the result of an increased frequency of breathing, an increased tidal volume, or a combination of both. It causes an excess intake of oxygen and the blowing off of carbon dioxide. [NIH] Hypnotic: A drug that acts to induce sleep. [EU] Hypotension: Abnormally low blood pressure. [NIH] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] 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] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Imaging procedures: Methods of producing pictures of areas inside the body. [NIH]
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Immune response: The activity of the immune system against foreign substances (antigens). [NIH]
Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]
effects
of
foreign
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] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [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] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Incubated: Grown in the laboratory under controlled conditions. (For instance, white blood cells can be grown in special conditions so that they attack specific cancer cells when returned to the body.) [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] 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]
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Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [NIH]
Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inositol: An isomer of glucose that has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insomnia: Difficulty in going to sleep or getting enough sleep. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracranial Aneurysm: A saclike dilatation of the walls of a blood vessel, usually an artery. [NIH]
Intracranial Hypertension: Increased pressure within the cranial vault. This may result from several conditions, including hydrocephalus; brain edema; intracranial masses; severe systemic hypertension; pseudotumor cerebri; and other disorders. [NIH] Intracranial Pressure: Pressure within the cranial cavity. It is influenced by brain mass, the circulatory system, CSF dynamics, and skull rigidity. [NIH] Intraoperative Period: The period during a surgical operation. [NIH] Intravenous: IV. Into a vein. [NIH] Intravenous Anesthetics: The systemic administration of an anesthetic drug via an injection into the vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Intubation: Introduction of a tube into a hollow organ to restore or maintain patency if obstructed. It is differentiated from catheterization in that the insertion of a catheter is usually performed for the introducing or withdrawing of fluids from the body. [NIH] Involuntary: Reaction occurring without intention or volition. [NIH] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a
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mechanical deformation. Ion channels which neurotransmitter receptors are not included. [NIH]
are
integral
parts
of
ionotropic
Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Irritable Bowel Syndrome: A disorder that comes and goes. Nerves that control the muscles in the GI tract are too active. The GI tract becomes sensitive to food, stool, gas, and stress. Causes abdominal pain, bloating, and constipation or diarrhea. Also called spastic colon or mucous colitis. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Isoflurane: A stable, non-explosive inhalation anesthetic, relatively free from significant side effects. [NIH] Isopropyl: A gene mutation inducer. [NIH] Jet lag: Symptoms produced in human beings by fast travel through large meridian difference. [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] Keto: It consists of 8 carbon atoms and within the endotoxins, it connects poysaccharide and lipid A. [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] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kidney Failure: The inability of a kidney to excrete metabolites at normal plasma levels under conditions of normal loading, or the inability to retain electrolytes under conditions of normal intake. In the acute form (kidney failure, acute), it is marked by uremia and usually by oliguria or anuria, with hyperkalemia and pulmonary edema. The chronic form (kidney failure, chronic) is irreversible and requires hemodialysis. [NIH] Kidney stone: A stone that develops from crystals that form in urine and build up on the inner surfaces of the kidney, in the renal pelvis, or in the ureters. [NIH] Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Lag: The time elapsing between application of a stimulus and the resulting reaction. [NIH] Lanthanum: The prototypical element in the rare earth family of metals. It has the atomic symbol La, atomic number 57, and atomic weight 138.91. Lanthanide ion is used in
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experimental biology as a calcium antagonist; lanthanum oxide improves the optical properties of glass. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Latency: The period of apparent inactivity between the time when a stimulus is presented and the moment a response occurs. [NIH] Lavage: A cleaning of the stomach and colon. Uses a special drink and enemas. [NIH] Lesion: An area of abnormal tissue change. [NIH] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]
Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Levorphanol: A narcotic analgesic that may be habit-forming. It is nearly as effective orally as by injection. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]
Ligands: A RNA simulation method developed by the MIT. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Liquor: 1. A liquid, especially an aqueous solution containing a medicinal substance. 2. A general term used in anatomical nomenclature for certain fluids of the body. [EU] Lithium: An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight 6.94. Salts of lithium are used in treating manic-depressive disorders. [NIH]
Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Lorazepam: An anti-anxiety agent with few side effects. It also has hypnotic, anticonvulsant, and considerable sedative properties and has been proposed as a preanesthetic agent. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]
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Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] 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] Maintenance therapy: Treatment that is given to help a primary (original) treatment keep working. Maintenance therapy is often given to help keep cancer in remission. [NIH] Manic: Affected with mania. [EU] Manic-depressive psychosis: One of a group of psychotic reactions, fundamentally marked by severe mood swings and a tendency to remission and recurrence. [NIH] Mannitol: A diuretic and renal diagnostic aid related to sorbitol. It has little significant energy value as it is largely eliminated from the body before any metabolism can take place. It can be used to treat oliguria associated with kidney failure or other manifestations of inadequate renal function and has been used for determination of glomerular filtration rate. Mannitol is also commonly used as a research tool in cell biological studies, usually to control osmolarity. [NIH] Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. [NIH] Medetomidine: An agonist of receptors, adrenergic alpha-2 that is used in veterinary medicine for its analgesic and sedative properties. It is the racemate of dexmedetomidine. [NIH]
Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medullary: Pertaining to the marrow or to any medulla; resembling marrow. [EU] Megaloblastic: A large abnormal red blood cell appearing in the blood in pernicious anaemia. [EU] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by
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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] Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells. [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] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Mental deficiency: A condition of arrested or incomplete development of mind from inherent causes or induced by disease or injury. [NIH] 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] Mephobarbital: A barbiturate that is metabolized to phenobarbital. It has been used for similar purposes, especially in epilepsy, but there is no evidence mephobarbital offers any advantage over phenobarbital. [NIH] Mesenteric: Pertaining to the mesentery : a membranous fold attaching various organs to the body wall. [EU] Mesentery: A layer of the peritoneum which attaches the abdominal viscera to the abdominal wall and conveys their blood vessels and nerves. [NIH] Mesolimbic: Inner brain region governing emotion and drives. [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metaplasia: A condition in which there is a change of one adult cell type to another similar adult cell type. [NIH] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Methanol: A colorless, flammable liquid used in the manufacture of formaldehyde and acetic acid, in chemical synthesis, antifreeze, and as a solvent. Ingestion of methanol is toxic and may cause blindness. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] Methohexital: An intravenous anesthetic with a short duration of action that may be used for induction of anesthesia. [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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Microdialysis: A technique for measuring extracellular concentrations of substances in tissues, usually in vivo, by means of a small probe equipped with a semipermeable membrane. Substances may also be introduced into the extracellular space through the membrane. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Midazolam: A short-acting compound, water-soluble at pH less than 4 and lipid-soluble at physiological pH. It is a hypnotic-sedative drug with anxiolytic and amnestic properties. It is used for sedation in dentistry, cardiac surgery, endoscopic procedures, as preanesthetic medication, and as an adjunct to local anesthesia. Because of its short duration and cardiorespiratory stability, it is particularly useful in poor-risk, elderly, and cardiac patients. [NIH]
Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Milliliter: A measure of volume for a liquid. A milliliter is approximately 950-times smaller than a quart and 30-times smaller than a fluid ounce. A milliliter of liquid and a cubic centimeter (cc) of liquid are the same. [NIH] Mineralization: The action of mineralizing; the state of being mineralized. [EU] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] 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] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU]
Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. [NIH] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoamine: Enzyme that breaks down dopamine in the astrocytes and microglia. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Mood Disorders: Those disorders that have a disturbance in mood as their predominant feature. [NIH] Morale: The prevailing temper or spirit of an individual or group in relation to the tasks or functions which are expected. [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] Morphogenesis: The development of the form of an organ, part of the body, or organism.
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[NIH]
Morphological: Relating to the configuration or the structure of live organs. [NIH] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Motor nerve: An efferent nerve conveying an impulse that excites muscular contraction. [NIH]
Movement Disorders: Syndromes which feature dyskinesias as a cardinal manifestation of the disease process. Included in this category are degenerative, hereditary, post-infectious, medication-induced, post-inflammatory, and post-traumatic conditions. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Muscarinic Agonists: Drugs that bind to and activate muscarinic cholinergic receptors (receptors, muscarinic). Muscarinic agonists are most commonly used when it is desirable to increase smooth muscle tone, especially in the GI tract, urinary bladder and the eye. They may also be used to reduce heart rate. [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] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] Myasthenia: Muscular debility; any constitutional anomaly of muscle. [EU] Mycoplasma: A genus of gram-negative, facultatively anaerobic bacteria bounded by a plasma membrane only. Its organisms are parasites and pathogens, found on the mucous membranes of humans, animals, and birds. [NIH] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Naive: Used to describe an individual who has never taken a certain drug or class of drugs (e. g., AZT-naive, antiretroviral-naive), or to refer to an undifferentiated immune system cell. [NIH] Narcosis: A general and nonspecific reversible depression of neuronal excitability, produced by a number of physical and chemical aspects, usually resulting in stupor. [NIH] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [EU] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes
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that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neuroleptic: A term coined to refer to the effects on cognition and behaviour of antipsychotic drugs, which produce a state of apathy, lack of initiative, and limited range of emotion and in psychotic patients cause a reduction in confusion and agitation and normalization of psychomotor activity. [EU] Neurologic: Having to do with nerves or the nervous system. [NIH] Neurology: A medical specialty concerned with the study of the structures, functions, and diseases of the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropharmacology: The branch of pharmacology dealing especially with the action of drugs upon various parts of the nervous system. [NIH] Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH] Neuroprotective Agents: Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids. [NIH] Neurotoxic: Poisonous or destructive to nerve tissue. [EU] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]
Neurotransmitters: Endogenous signaling molecules that alter the behavior of neurons or effector cells. Neurotransmitter is used here in its most general sense, including not only messengers that act directly to regulate ion channels, but also those that act through second messenger systems, and those that act at a distance from their site of release. Included are neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not acting at synapses. [NIH] Nickel: A trace element with the atomic symbol Ni, atomic number 28, and atomic weight 58.69. It is a cofactor of the enzyme urease. [NIH] Nicotine: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. [NIH]
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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] Nitrous Oxide: Nitrogen oxide (N2O). A colorless, odorless gas that is used as an anesthetic and analgesic. High concentrations cause a narcotic effect and may replace oxygen, causing death by asphyxia. It is also used as a food aerosol in the preparation of whipping cream. [NIH]
Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Odour: A volatile emanation that is perceived by the sense of smell. [EU] Oliguria: Clinical manifestation of the urinary system consisting of a decrease in the amount of urine secreted. [NIH] Oocytes: Female germ cells in stages between the prophase of the first maturation division and the completion of the second maturation division. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] 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] Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [NIH] Oral Hygiene: The practice of personal hygiene of the mouth. It includes the maintenance of oral cleanliness, tissue tone, and general preservation of oral health. [NIH] Oral Manifestations: Disorders of the mouth attendant upon non-oral disease or injury. [NIH]
Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Orthostatic: Pertaining to or caused by standing erect. [EU] Osmolarity: The concentration of osmotically active particles expressed in terms of osmoles of solute per litre of solution. [EU] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Ovarian Follicle: Spheroidal cell aggregation in the ovary containing an ovum. It consists of an external fibro-vascular coat, an internal coat of nucleated cells, and a transparent, albuminous fluid in which the ovum is suspended. [NIH] Overdose: An accidental or deliberate dose of a medication or street drug that is in excess of what is normally used. [NIH] Ovulation: The discharge of a secondary oocyte from a ruptured graafian follicle. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] 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
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molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]
Palladium: A chemical element having an atomic weight of 106.4, atomic number of 46, and the symbol Pd. It is a white, ductile metal resembling platinum, and following it in abundance and importance of applications. It is used in dentistry in the form of gold, silver, and copper alloys. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Palsy: Disease of the peripheral nervous system occurring usually after many years of increased lead absorption. [NIH] Panic: A state of extreme acute, intense anxiety and unreasoning fear accompanied by disorganization of personality function. [NIH] Panic Disorder: A type of anxiety disorder characterized by unexpected panic attacks that last minutes or, rarely, hours. Panic attacks begin with intense apprehension, fear or terror and, often, a feeling of impending doom. Symptoms experienced during a panic attack include dyspnea or sensations of being smothered; dizziness, loss of balance or faintness; choking sensations; palpitations or accelerated heart rate; shakiness; sweating; nausea or other form of abdominal distress; depersonalization or derealization; paresthesias; hot flashes or chills; chest discomfort or pain; fear of dying and fear of not being in control of oneself or going crazy. Agoraphobia may also develop. Similar to other anxiety disorders, it may be inherited as an autosomal dominant trait. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Paresthesias: Abnormal touch sensations, such as burning or prickling, that occur without an outside stimulus. [NIH] Parkinsonism: A group of neurological disorders characterized by hypokinesia, tremor, and muscular rigidity. [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] Patch-Clamp Techniques: An electrophysiologic technique for studying cells, cell membranes, and occasionally isolated organelles. All patch-clamp methods rely on a very high-resistance seal between a micropipette and a membrane; the seal is usually attained by gentle suction. The four most common variants include on-cell patch, inside-out patch, outside-out patch, and whole-cell clamp. Patch-clamp methods are commonly used to voltage clamp, that is control the voltage across the membrane and measure current flow, but current-clamp methods, in which the current is controlled and the voltage is measured, are also used. [NIH] Pathogen: Any disease-producing microorganism. [EU] Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Patient Education: The teaching or training of patients concerning their own health needs. [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] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood
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vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peripheral Vascular Disease: Disease in the large blood vessels of the arms, legs, and feet. People who have had diabetes for a long time may get this because major blood vessels in their arms, legs, and feet are blocked and these limbs do not receive enough blood. The signs of PVD are aching pains in the arms, legs, and feet (especially when walking) and foot sores that heal slowly. Although people with diabetes cannot always avoid PVD, doctors say they have a better chance of avoiding it if they take good care of their feet, do not smoke, and keep both their blood pressure and diabetes under good control. [NIH] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Pharmacodynamics: The study of the biochemical and physiological effects of drugs and the mechanisms of their actions, including the correlation of actions and effects of drugs with their chemical structure; also, such effects on the actions of a particular drug or drugs. [EU] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Phenobarbital: A barbituric acid derivative that acts as a nonselective central nervous system depressant. It promotes binding to inhibitory GABA subtype receptors, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations. [NIH] Phenyl: Ingredient used in cold and flu remedies. [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] Phosphorylase: An enzyme of the transferase class that catalyzes the phosphorylysis of a terminal alpha-1,4-glycosidic bond at the non-reducing end of a glycogen molecule, releasing a glucose 1-phosphate residue. Phosphorylase should be qualified by the natural substance acted upon. EC 2.4.1.1. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] 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
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cells, tissues, and organs. [NIH] Picrotoxin: A noncompetitive antagonist at GABA-A receptors and thus a convulsant. Picrotoxin blocks the GABA-activated chloride ionophore. Although it is most often used as a research tool, it has been used as a CNS stimulant and an antidote in poisoning by CNS depressants, especially the barbiturates. [NIH] Pipette: Tube designed to measure liquids in drops. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]
Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., polypeptides, proteins, plastics). [NIH] 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] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Polystyrenes: Polymerized forms of styrene used as a biocompatible material, especially in dentistry. They are thermoplastic and are used as insulators, for injection molding and casting, as sheets, plates, rods, rigid forms and beads. [NIH] Porphyria: A group of disorders characterized by the excessive production of porphyrins or their precursors that arises from abnormalities in the regulation of the porphyrin-heme pathway. The porphyrias are usually divided into three broad groups, erythropoietic, hepatic, and erythrohepatic, according to the major sites of abnormal porphyrin synthesis. [NIH]
Porphyrins: A group of compounds containing the porphin structure, four pyrrole rings connected by methine bridges in a cyclic configuration to which a variety of side chains are
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attached. The nature of the side chain is indicated by a prefix, as uroporphyrin, hematoporphyrin, etc. The porphyrins, in combination with iron, form the heme component in biologically significant compounds such as hemoglobin and myoglobin. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postoperative: After surgery. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-synaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potassium Channels: Cell membrane glycoproteins selective for potassium ions. [NIH] Potassium hydroxide: A toxic and highly corrosive chemical used to make soap, in bleaching, and as a paint remover. It is used in small amounts as a food additive and in the preparatrion of some drugs. [NIH] Potentiate: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiating: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precipitation: The act or process of precipitating. [EU] 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] Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states. [NIH] Prednisone: A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. [NIH] Premedication: Preliminary administration of a drug preceding a diagnostic, therapeutic, or surgical procedure. The commonest types of premedication are antibiotics (antibiotic prophylaxis) and anti-anxiety agents. It does not include preanesthetic medication. [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH]
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Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Propofol: A widely used anesthetic. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (endopeptidases). [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] 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] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pruritus: An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. [NIH] Pseudotumor Cerebri: A condition marked by raised intracranial pressure and characterized clinically by headaches; nausea; papilledema, peripheral constriction of the visual fields, transient visual obscurations, and pulsatile tinnitus. Obesity is frequently associated with this condition, which primarily affects women between 20 and 44 years of age. Chronic papilledema may lead to optic nerve injury (optic nerve diseases) and visual loss (blindness). [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU]
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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 described in psychotic patients, although many patients with the disorder are not judged psychotic. [EU] Psychotomimetic: Psychosis miming. [NIH] Psychotropic: Exerting an effect upon the mind; capable of modifying mental activity; usually applied to drugs that effect the mental state. [EU] Psychotropic Drugs: A loosely defined grouping of drugs that have effects on psychological function. Here the psychotropic agents include the antidepressive agents, hallucinogens, and tranquilizing agents (including the antipsychotics and anti-anxiety agents). [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] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]
Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Edema: An accumulation of an excessive amount of watery fluid in the lungs, may be caused by acute exposure to dangerous concentrations of irritant gasses. [NIH] Pulmonary Ventilation: The total volume of gas per minute inspired or expired measured in liters per minute. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]
Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Purulent: Consisting of or containing pus; associated with the formation of or caused by pus. [EU] Pyoderma: Any purulent skin disease (Dorland, 27th ed). [NIH] Pyoderma Gangrenosum: An idiopathic, rapidly evolving, and severely debilitating disease occurring most commonly in association with chronic ulcerative colitis. It is characterized by the presence of boggy, purplish ulcers with undermined borders, appearing mostly on the legs. The majority of cases are in people between 40 and 60 years old. Its etiology is unknown. [NIH]
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Pyridoxal: 3-Hydroxy-5-(hydroxymethyl)-2-methyl-4- pyridinecarboxaldehyde. [NIH] Quaternary: 1. Fourth in order. 2. Containing four elements or groups. [EU] Quiescent: Marked by a state of inactivity or repose. [EU] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radioactive: Giving off radiation. [NIH] Radioisotope: An unstable element that releases radiation as it breaks down. Radioisotopes can be used in imaging tests or as a treatment for cancer. [NIH] 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] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Reality Testing: The individual's objective evaluation of the external world and the ability to differentiate adequately between it and the internal world; considered to be a primary ego function. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Adrenergic: Cell-surface proteins that bind epinephrine and/or norepinephrine with high affinity and trigger intracellular changes. The two major classes of adrenergic receptors, alpha and beta, were originally discriminated based on their cellular actions but now are distinguished by their relative affinity for characteristic synthetic ligands. Adrenergic receptors may also be classified according to the subtypes of G-proteins with which they bind; this scheme does not respect the alpha-beta distinction. [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] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflux: The term used when liquid backs up into the esophagus from the stomach. [NIH] Refractory: Not readily yielding to treatment. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Relaxant: 1. Lessening or reducing tension. 2. An agent that lessens tension. [EU]
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Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Response rate: The percentage of patients whose cancer shrinks or disappears after treatment. [NIH] Retinoid: Vitamin A or a vitamin A-like compound. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Rod: A reception for vision, located in the retina. [NIH] Rubber: A high-molecular-weight polymeric elastomer derived from the milk juice (latex) of Hevea brasiliensis and other trees. It is a substance that can be stretched at room temperature to atleast twice its original length and after releasing the stress, retractrapidly, and recover its original dimensions fully. Synthetic rubber is made from many different chemicals, including styrene, acrylonitrile, ethylene, propylene, and isoprene. [NIH] Ruthenium: A hard, brittle, grayish-white rare earth metal with an atomic symbol Ru, atomic number 44, and atomic weight 101.07. It is used as a catalyst and hardener for platinum and palladium. [NIH] Saline: A solution of salt and water. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Saponification: The hydrolysis of an ester into an alcohol and acid. [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] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH]
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Scopolamine: An alkaloid from Solanaceae, especially Datura metel L. and Scopola carniolica. Scopolamine and its quaternary derivatives act as antimuscarinics like atropine, but may have more central nervous system effects. Among the many uses are as an anesthetic premedication, in urinary incontinence, in motion sickness, as an antispasmodic, and as a mydriatic and cycloplegic. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Secobarbital: A barbiturate that is used as a sedative. Secobarbital is reported to have no anti-anxiety activity. [NIH] Second Messenger Systems: Systems in which an intracellular signal is generated in response to an intercellular primary messenger such as a hormone or neurotransmitter. They are intermediate signals in cellular processes such as metabolism, secretion, contraction, phototransduction, and cell growth. Examples of second messenger systems are the adenyl cyclase-cyclic AMP system, the phosphatidylinositol diphosphate-inositol triphosphate system, and the cyclic GMP system. [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] 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] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sensibility: The ability to receive, feel and appreciate sensations and impressions; the quality of being sensitive; the extend to which a method gives results that are free from false negatives. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] 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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Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Sleep apnea: A serious, potentially life-threatening breathing disorder characterized by repeated cessation of breathing due to either collapse of the upper airway during sleep or absence of respiratory effort. [NIH] Small 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]
Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solitary Nucleus: Gray matter located in the dorsomedial part of the medulla oblongata associated with the solitary tract. The solitary nucleus receives inputs from most organ systems including the terminations of the facial, glossopharyngeal, and vagus nerves. It is a major coordinator of autonomic nervous system regulation of cardiovascular, respiratory, gustatory, gastrointestinal, and chemoreceptive aspects of homeostasis. The solitary nucleus is also notable for the large number of neurotransmitters which are found therein. [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] Sorbitol: A polyhydric alcohol with about half the sweetness of sucrose. Sorbitol occurs naturally and is also produced synthetically from glucose. It was formerly used as a diuretic and may still be used as a laxative and in irrigating solutions for some surgical procedures. It is also used in many manufacturing processes, as a pharmaceutical aid, and in several research applications. [NIH] Spastic: 1. Of the nature of or characterized by spasms. 2. Hypertonic, so that the muscles are stiff and the movements awkward. 3. A person exhibiting spasticity, such as occurs in spastic paralysis or in cerebral palsy. [EU] Spasticity: A state of hypertonicity, or increase over the normal tone of a muscle, with
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heightened deep tendon reflexes. [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] Sprue: A non febrile tropical disease of uncertain origin. [NIH] Stabilization: The creation of a stable state. [EU] Status Epilepticus: Repeated and prolonged epileptic seizures without recovery of consciousness between attacks. [NIH] Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [NIH] Steroids: Drugs used to relieve swelling and inflammation. [NIH] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]
Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Strychnine: An alkaloid found in the seeds of nux vomica. It is a competitive antagonist at glycine receptors and thus a convulsant. It has been used as an analeptic, in the treatment of nonketotic hyperglycinemia and sleep apnea, and as a rat poison. [NIH] Stupor: Partial or nearly complete unconsciousness, manifested by the subject's responding only to vigorous stimulation. Also, in psychiatry, a disorder marked by reduced responsiveness. [EU] Styrene: A colorless, toxic liquid with a strong aromatic odor. It is used to make rubbers, polymers and copolymers, and polystyrene plastics. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other
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disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substrate: A substance upon which an enzyme acts. [EU] Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Sulfuric acid: A strong acid that, when concentrated is extemely corrosive to the skin and mucous membranes. It is used in making fertilizers, dyes, electroplating, and industrial explosives. [NIH] 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] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Symptomatic treatment: Therapy that eases symptoms without addressing the cause of disease. [NIH] Synapses: Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate through direct electrical connections which are sometimes called electrical synapses; these are not included here but rather in gap junctions. [NIH] Synapsis: The pairing between homologous chromosomes of maternal and paternal origin during the prophase of meiosis, leading to the formation of gametes. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] 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]
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Synaptic Vesicles: Membrane-bound compartments which contain transmitter molecules. Synaptic vesicles are concentrated at presynaptic terminals. They actively sequester transmitter molecules from the cytoplasm. In at least some synapses, transmitter release occurs by fusion of these vesicles with the presynaptic membrane, followed by exocytosis of their contents. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tardive: Marked by lateness, late; said of a disease in which the characteristic lesion is late in appearing. [EU] Taurine: 2-Aminoethanesulfonic acid. A conditionally essential nutrient, important during mammalian development. It is present in milk but is isolated mostly from ox bile and strongly conjugates bile acids. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetrahydrocannabinol: A psychoactive compound extracted from the resin of Cannabis sativa (marihuana, hashish). The isomer delta-9-tetrahydrocannabinol (THC) is considered the most active form, producing characteristic mood and perceptual changes associated with this compound. Dronabinol is a synthetic form of delta-9-THC. [NIH] Theophylline: Alkaloid obtained from Thea sinensis (tea) and others. It stimulates the heart and central nervous system, dilates bronchi and blood vessels, and causes diuresis. The drug is used mainly in bronchial asthma and for myocardial stimulation. Among its more prominent cellular effects are inhibition of cyclic nucleotide phosphodiesterases and antagonism of adenosine receptors. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thiamine: 3-((4-Amino-2-methyl-5-pyrimidinyl)methyl)-5-(2methylthiazolium chloride. [NIH]
hydroxyethyl)-4-
Thiobarbiturates: Compounds in which one or more of the ketone groups on the pyrimidine ring of barbituric acid are replaced by thione groups. [NIH] Thiourea: A photographic fixative used also in the manufacture of resins. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), this substance may reasonably be anticipated to be a carcinogen (Merck Index, 9th ed). Many of its derivatives are antithryoid agents and/or free radical scavengers. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]
Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH]
Dictionary 145
Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Tidal Volume: The volume of air inspired or expired during each normal, quiet respiratory cycle. Common abbreviations are TV or V with subscript T. [NIH] Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic number 50, and atomic weight 118.71. [NIH] 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] Tonic: 1. Producing and restoring the normal tone. 2. Characterized by continuous tension. 3. A term formerly used for a class of medicinal preparations believed to have the power of restoring normal tone to tissue. [EU] Tonicity: The normal state of muscular tension. [NIH] Topical: On the surface of the body. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Tracer: A substance (such as a radioisotope) used in imaging procedures. [NIH] Traction: The act of pulling. [NIH] Tranquilizing Agents: A traditional grouping of drugs said to have a soothing or calming effect on mood, thought, or behavior. Included here are the anti-anxiety agents (minor tranquilizers), antimanic agents, and the antipsychotic agents (major tranquilizers). These drugs act by different mechanisms and are used for different therapeutic purposes. [NIH] 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] 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]
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Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Trees: Woody, usually tall, perennial higher plants (Angiosperms, Gymnosperms, and some Pterophyta) having usually a main stem and numerous branches. [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] Tricyclic: Containing three fused rings or closed chains in the molecular structure. [EU] Trigger zone: Dolorogenic zone (= producing or causing pain). [EU] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Ulcerative colitis: Chronic inflammation of the colon that produces ulcers in its lining. This condition is marked by abdominal pain, cramps, and loose discharges of pus, blood, and mucus from the bowel. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Univalent: Pertaining to an unpaired chromosome during the zygotene stage of prophase to first metaphase in meiosis. [NIH] Uracil: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH] Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [NIH] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]
Uric: A kidney stone that may result from a diet high in animal protein. When the body breaks down this protein, uric acid levels rise and can form stones. [NIH] Uridine Phosphorylase: An enzyme that catalyzes the transfer of ribose from uridine to orthophosphate, forming uracil and ribose 1-phosphate. EC 2.4.2.3. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH]
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Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilators: Any nerve or agent which induces dilatation of the 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] Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide back for gas exchange. [NIH] Ventilation: 1. In respiratory physiology, the process of exchange of air between the lungs and the ambient air. Pulmonary ventilation (usually measured in litres per minute) refers to the total exchange, whereas alveolar ventilation refers to the effective ventilation of the alveoli, in which gas exchange with the blood takes place. 2. In psychiatry, verbalization of one's emotional problems. [EU] Ventral: 1. Pertaining to the belly or to any venter. 2. Denoting a position more toward the belly surface than some other object of reference; same as anterior in human anatomy. [EU] 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] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertigo: An illusion of movement; a sensation as if the external world were revolving around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo). The term is sometimes erroneously used to mean any form of dizziness. [EU] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] 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] Virus Diseases: A general term for diseases produced by viruses. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visceral Afferents: The sensory fibers innervating the viscera. [NIH] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH]
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Vomica: The profuse and sudden expectoration of pus and putrescent matter. An abnormal cavity in an organ especially in the lung, caused by suppuration and the breaking down of tissue. [NIH] Wakefulness: A state in which there is an enhanced potential for sensitivity and an efficient responsiveness to external stimuli. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]
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] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xanthine: An urinary calculus. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]
149
INDEX 2 2-Propanol, 44, 95 A Abdomen, 95, 102, 103, 123, 125, 142 Abdominal, 95, 117, 124, 127, 132, 146 Abdominal Pain, 95, 117, 124, 146 Acceptor, 95, 125, 131 Acetone, 44, 95, 124 Acetylcholine, 13, 30, 60, 95, 106 Acidosis, 4, 95 Acrylonitrile, 95, 139 Acyl, 95, 115 Adaptability, 95, 105 Adaptation, 95, 134 Adenine, 95, 137 Adenosine, 5, 95, 133, 144 Adjuvant, 95, 116, 117 Adrenal Cortex, 95, 136 Adrenal Medulla, 96, 114 Adrenergic, 96, 99, 100, 112, 114, 138, 143 Adverse Effect, 96, 140 Aerosol, 13, 96, 131 Affinity, 6, 24, 96, 111, 138, 141 Ageing, 50, 96 Agonist, 6, 14, 50, 58, 60, 96, 101, 103, 112, 126, 130 Akathisia, 96, 100 Alanine, 50, 96 Alexia, 96, 113 Algorithms, 96, 102 Alkaline, 45, 47, 95, 96, 97, 104 Alkaloid, 34, 96, 101, 102, 103, 107, 128, 130, 140, 142, 144 Alkylating Agents, 96, 146 Alkylation, 44, 96 Allergen, 97, 111 Allylamine, 97 Alpha-1, 8, 9, 97, 133 Alternative medicine, 66, 97 Aluminum, 44, 97 Amination, 44, 97 Amine, 52, 97, 120 Amino Acid Sequence, 97, 99 Amino Acids, 55, 97, 101, 115, 132, 134, 136, 139, 140, 145, 146 Aminophylline, 56, 97 Ammonia, 26, 97, 146 Amnesia, 61, 97
Amnestic, 97, 128 Amphetamine, 4, 97, 98, 111 Anabolic, 64, 97, 98 Anabolic Steroids, 64, 98 Anaerobic, 98, 129 Anaesthesia, 26, 30, 98, 122 Analeptic, 98, 142 Analgesic, 24, 98, 103, 107, 111, 125, 126, 128, 131 Analog, 52, 98, 111, 116 Analogous, 15, 98, 145 Analytes, 47, 48, 52, 98 Anatomical, 98, 109, 122, 125, 139 Anemia, 4, 42, 98 Anesthesia, 11, 18, 20, 21, 22, 23, 25, 30, 34, 57, 59, 61, 98, 99, 110, 114, 124, 127, 128 Anesthetics, 4, 6, 9, 12, 13, 14, 16, 36, 58, 98, 101, 114 Aneurysm, 11, 98 Angiogenesis, 98, 126 Animal model, 10, 98 Anions, 98, 124 Anisotropy, 98, 116 Anorexia, 59, 60, 98, 117 Antagonism, 99, 126, 144 Anti-Anxiety Agents, 99, 135, 137, 145 Antibiotic, 4, 99, 132, 135 Antibiotic Prophylaxis, 4, 99, 135 Antibodies, 15, 43, 48, 52, 99, 100, 114, 119, 126, 134 Antibody, 4, 43, 96, 99, 108, 116, 119, 120, 122, 128, 142 Anticoagulant, 99, 136 Anticonvulsant, 99, 106, 125 Antidepressive Agents, 99, 137 Antidote, 54, 99, 116, 134 Antiemetic, 99, 100, 107 Antiepileptic, 61, 99 Antigen, 43, 96, 99, 100, 108, 116, 120, 121, 122 Anti-infective, 99, 121 Anti-inflammatory, 99, 118, 135 Antimetabolite, 99, 111, 116 Antineoplastic, 42, 96, 99, 116 Antipsychotic, 4, 100, 130, 145 Antipsychotic Agents, 4, 100, 145 Antiseptic, 95, 100 Antiserum, 45, 47, 100
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Antispasmodic, 100, 131, 140 Antitussive, 100, 111, 131 Antiviral, 42, 100 Antiviral Agents, 42, 100 Anxiety, 6, 8, 10, 59, 60, 96, 99, 100, 125, 132, 140 Anxiety Disorders, 100, 132 Anxiolytic, 4, 100, 103, 106, 128 Aqueous, 42, 45, 47, 49, 56, 100, 102, 110, 121, 125 Aromatic, 43, 100, 142 Arterial, 97, 100, 103, 106, 121, 136, 144 Arteries, 100, 102, 103, 109, 127 Aspartate, 49, 55, 100, 111, 124 Aspartic, 55, 100, 101, 114, 115 Aspartic Acid, 55, 100, 101 Asphyxia, 49, 101, 131 Assay, 17, 43, 47, 53, 54, 60, 65, 101, 116, 122 Atmospheric Pressure, 44, 101 Atropine, 101, 140 Auditory, 101, 107 Auditory Cortex, 101, 107 Autonomic, 21, 95, 100, 101, 133, 141, 143 Autonomic Nervous System, 21, 101, 133, 141, 143 B Baclofen, 11, 101 Bacteria, 95, 99, 101, 114, 118, 127, 128, 129, 145 Bactericidal, 101, 115 Bacteriophage, 101, 145 Barbital, 43, 48, 101 Basal Ganglia, 100, 101, 103, 106 Basal Ganglia Diseases, 101, 106 Base, 15, 45, 53, 95, 102, 110, 111, 119, 124 Benign, 102, 119 Benzene, 13, 102 Benzodiazepines, 4, 6, 8, 10, 11, 12, 13, 14, 15, 16, 24, 25, 30, 31, 50, 59, 60, 61, 64, 102, 103, 116 Benzoic Acid, 33, 102 Bicuculline, 6, 14, 102 Bile, 102, 125, 144 Bile Acids, 102, 144 Binding Sites, 9, 14, 16, 54, 102 Bioassay, 33, 102 Biochemical, 23, 34, 56, 59, 99, 102, 133, 140 Biosynthesis, 102, 136, 140 Biotechnology, 16, 17, 66, 77, 102 Bipolar Disorder, 4, 59, 60, 102
Bladder, 19, 102, 122, 129, 146 Bloating, 102, 124 Blood Coagulation, 102, 104, 144 Blood pressure, 11, 92, 102, 105, 106, 121, 128, 133, 141 Blood vessel, 98, 102, 103, 105, 106, 107, 114, 123, 124, 126, 127, 133, 141, 142, 144, 147 Blood-Brain Barrier, 54, 103 Body Fluids, 42, 54, 103, 113, 141 Bone Marrow, 18, 102, 103, 110, 126 Bowel, 103, 123, 142, 146 Brain Infarction, 59, 103 Brain Stem, 103, 106, 107 Brain Stem Infarctions, 103 Branch, 89, 103, 113, 126, 130, 132, 137, 142, 144 Breakdown, 103, 112, 117 Bromine, 51, 103 Bromine Compounds, 51, 103 Bronchi, 103, 114, 144 Bronchial, 97, 103, 120, 144 Bulimia, 59, 60, 103 Buprenorphine, 25, 103 Buspirone, 4, 103 Butadienes, 45, 103 Butyric Acid, 55, 103 C Calcium, 13, 44, 47, 55, 104, 107, 108, 116, 125, 126, 141 Calcium Carbonate, 44, 104 Calcium Hydroxide, 45, 104 Calcium Sulfate, 47, 104 Calculi, 104, 118 Calmodulin, 104, 116 Cannabidiol, 104 Cannabinoids, 25, 53, 104 Cannabinol, 104 Cannabis, 63, 64, 104, 144 Capillary, 104, 118, 147 Carbohydrates, 104, 105 Carbon Dioxide, 104, 121, 134, 139, 147 Carboxy, 42, 104 Carcinogen, 104, 144 Carcinogenesis, 31, 104 Carcinogenic, 96, 102, 104, 123 Cardiac, 20, 49, 58, 59, 60, 97, 104, 113, 114, 115, 128, 129 Cardiac arrest, 49, 104 Cardiorespiratory, 104, 128 Cardiovascular, 4, 25, 97, 105, 115, 140, 141
Index 151
Cardiovascular disease, 4, 105 Cardiovascular System, 105, 115 Case report, 22, 105 Catheterization, 105, 123 Cathode, 105, 113 Cations, 14, 105, 124 Cause of Death, 59, 105 Cell Communication, 15, 105 Cell Death, 21, 49, 105, 130 Cell Division, 101, 105, 126, 134, 136 Cell Extracts, 14, 105 Cell membrane, 12, 105, 111, 117, 132, 133, 135 Cellulose, 104, 105, 134 Central Nervous System Infections, 105, 119, 120 Cerebellar, 34, 105, 107 Cerebellum, 103, 105, 106 Cerebral, 5, 20, 26, 52, 59, 101, 103, 106, 109, 110, 114, 120, 137, 141 Cerebral hemispheres, 101, 103, 106 Cerebral Infarction, 103, 106, 120 Cerebral Palsy, 106, 141 Cerebrovascular, 101, 105, 106 Cerebrum, 106 Chemoreceptor, 100, 106 Chemotherapy, 42, 106 Chlordiazepoxide, 8, 106 Chlorine, 50, 51, 106 Choline, 31, 106 Cholinergic, 55, 59, 60, 100, 106, 129, 130 Cholinergic Agents, 55, 106 Chorea, 59, 60, 100, 106 Choreatic Disorders, 106 Chromosomal, 10, 107 Chromosome, 107, 119, 125, 146 Chronic, 3, 7, 8, 10, 30, 55, 59, 60, 92, 103, 107, 114, 117, 122, 124, 136, 137, 142, 146 Chronic renal, 3, 107, 117 Cinnarizine, 52, 107 Circulatory system, 107, 123 Clamp, 13, 107, 132 Clinical trial, 5, 6, 77, 107, 110, 138 Cloning, 10, 102, 107 Coal, 102, 107 Coca, 107 Cocaine, 59, 60, 64, 107 Cochlea, 107 Cochlear, 35, 107 Cochlear Nerve, 107 Cochlear Nucleus, 35, 107 Codeine, 4, 70, 107, 111, 131
Coenzyme, 108, 116 Cofactor, 108, 130, 136, 144 Colitis, 108, 124 Collagen, 51, 108, 115, 117, 126, 136 Comatose, 43, 108 Complement, 108, 117 Complementary and alternative medicine, 33, 38, 108 Complementary medicine, 33, 108 Computational Biology, 77, 108 Congestion, 100, 109 Conjugated, 102, 109, 110 Connective Tissue, 103, 108, 109, 116, 117, 125 Consciousness, 98, 99, 109, 110, 111, 112, 142 Constipation, 100, 109, 124 Constriction, 109, 124, 136, 147 Constriction, Pathologic, 109, 147 Consumption, 64, 109, 117, 139 Contraindications, ii, 109 Convulsions, 99, 101, 102, 109, 130 Coordination, 53, 106, 109 Coronary, 105, 109, 127 Coronary heart disease, 105, 109 Coronary Thrombosis, 109, 127 Corpus, 109, 136 Corpus Luteum, 109, 136 Cortex, 11, 109 Cortical, 12, 14, 109, 115, 140 Cortisone, 109, 135 Cranial, 106, 107, 109, 119, 123, 133 Craniocerebral Trauma, 101, 109, 119, 120 Craniotomy, 11, 110 Curare, 110, 129 Curative, 110, 144 Cutaneous, 35, 50, 51, 110 Cyclic, 27, 104, 105, 110, 134, 140, 144 Cyclosporine, 4, 110 Cysteine, 9, 16, 110, 114 Cystine, 110 Cytochrome, 34, 82, 110 Cytoplasm, 105, 110, 114, 139, 144 Cytoskeleton, 12, 110 D Databases, Bibliographic, 77, 110 Deamination, 110, 146 Delirium, 100, 110 Delusions, 111, 137 Dementia, 60, 100, 111 Dendrites, 111, 130 Density, 14, 45, 51, 111, 131
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Barbiturates
Dental Care, 3, 111 Deoxyuridine, 42, 111 Depersonalization, 111, 132, 139 Depolarization, 8, 30, 111, 141 Derealization, 111, 132 Desensitization, 6, 14, 111 Detoxification, 25, 111 Deuterium, 111, 121 Dexmedetomidine, 111, 126 Dextroamphetamine, 97, 111 Dextromethorphan, 55, 111 Diagnostic procedure, 41, 66, 111 Diarrhea, 58, 112, 124 Diastolic, 112, 121 Diffusion, 112, 123 Digestion, 102, 103, 112, 123, 125, 142 Digestive tract, 112, 141 Dilatation, 98, 112, 123, 135, 147 Dimethyl, 53, 56, 58, 112 Diploid, 112, 134 Direct, iii, 7, 14, 20, 21, 23, 55, 69, 105, 112, 126, 138, 143 Disinfectant, 95, 112, 115 Dissociation, 96, 112 Distal, 112, 113, 136 Diuresis, 22, 112, 144 Diuretic, 112, 117, 126, 141 Dizziness, 112, 132, 147 Dopamine, 97, 100, 107, 111, 112, 128 Dorsal, 35, 107, 112, 135 Dorsum, 112 Dose-dependent, 8, 13, 112 Drug Interactions, 4, 70, 71, 112 Drug Tolerance, 113, 145 Duct, 105, 113, 132, 139 Duodenum, 102, 113, 114, 142 Dyes, 113, 143 Dyskinesia, 59, 60, 100, 113 Dyslexia, 59, 60, 113 Dyspnea, 113, 132 Dystonia, 59, 60, 100, 113 E Eating Disorders, 33, 113 Edema, 58, 113, 117, 123 Effector, 95, 108, 113, 130 Effector cell, 113, 130 Efficacy, 9, 11, 22, 42, 103, 113 Elastin, 108, 113, 115 Elective, 113 Electrode, 13, 105, 113 Electrolysis, 98, 105, 113 Electrolyte, 3, 110, 113, 135, 141
Electrons, 102, 105, 113, 124, 132, 138 Electrophysiological, 6, 12, 113 Electroplating, 113, 143 Embolus, 114, 122 Emesis, 92, 100, 114 Emetic, 59, 60, 114 Empyema, 22, 114 Endocrine Glands, 114 Endopeptidases, 114, 136 Endoscopic, 114, 128 Endothelial cell, 103, 114, 144 Endotoxins, 108, 114, 124 End-stage renal, 107, 114 Enflurane, 9, 56, 114 Enteric Nervous System, 30, 114 Environmental Health, 76, 78, 114 Enzymatic, 104, 108, 114, 115, 120 Enzyme, 52, 54, 108, 113, 114, 127, 128, 130, 133, 134, 136, 141, 143, 144, 146, 147, 148 Enzyme Multiplied Immunoassay Technique, 54, 114 Epinephrine, 25, 96, 112, 114, 138 Epithelial, 114, 115, 120 Epithelial Cells, 115, 120 Ergot, 115, 126 Erythrocytes, 98, 103, 115, 138 Esophagus, 112, 115, 138, 142 Esterification, 44, 115 Ethanol, 6, 8, 10, 13, 31, 34, 39, 44, 115 Ether, 9, 115 Etomidate, 9, 11, 23, 56, 115 Euthanasia, 25, 115 Excipient, 104, 115 Excitability, 15, 48, 115, 129 Excitatory, 9, 55, 101, 115, 118, 130 Excitatory Amino Acids, 115, 130 Excitotoxicity, 5, 115 Extracellular, 9, 12, 14, 109, 115, 116, 126, 128, 141 Extracellular Matrix, 109, 115, 126 Extracellular Matrix Proteins, 115, 126 Extracellular Space, 115, 116, 128 Extraction, 17, 43, 116 Extrapyramidal, 96, 100, 112, 116 F Family Planning, 77, 116 Fat, 103, 104, 109, 114, 116, 124, 125, 141 Febrile, 116, 142 Fentanyl, 20, 116 Fertilizers, 116, 143 Fetal Alcohol Syndrome, 64, 116
Index 153
Fibrosis, 97, 116, 139 Filtration, 47, 116 Flame Retardants, 51, 116 Flatus, 116, 117 Flumazenil, 7, 116 Flunarizine, 52, 116 Fluorescence, 20, 24, 47, 48, 116 Fluorescence Polarization, 20, 24, 47, 48, 116 Fluorescence Polarization Immunoassay, 20, 24, 47, 48, 116 Fluorouracil, 42, 116 Folate, 111, 117 Fold, 117, 127 Forearm, 102, 117 Free Radical Scavengers, 117, 144 Fungistatic, 102, 117 Furosemide, 14, 117 G Gallic Acid, 33, 117 Ganglia, 95, 101, 114, 117, 130, 133, 143 Gap Junctions, 117, 143 Gas, 18, 43, 97, 104, 106, 112, 116, 117, 120, 121, 124, 131, 137, 143, 147 Gasoline, 102, 117 Gastric, 59, 60, 92, 117, 120 Gastric Acid, 59, 60, 117 Gastroenteritis, 103, 117 Gastrointestinal, 4, 114, 115, 117, 140, 141 Gastrointestinal tract, 115, 117, 140 Gelatin, 117, 118, 144 Gene, 10, 34, 102, 117, 124, 134 Genetic Engineering, 102, 107, 117 Germ Cells, 117, 126, 131 Gestation, 118, 133, 134 Gland, 95, 96, 109, 118, 125, 140, 142 Glomerular, 118, 126, 139 Glomerular Filtration Rate, 118, 126 Glucocorticoid, 118, 135 Glucose, 21, 23, 105, 118, 119, 123, 133, 141 Glucuronic Acid, 118, 119 Glutamate, 5, 30, 55, 111, 115, 118, 133 Glutamic Acid, 118, 136 Glycerol, 104, 118, 133 Glycine, 6, 12, 50, 54, 102, 118, 140, 142 Glycogen, 118, 133 Glycols, 118, 121 Glycosidic, 118, 133 Gout, 55, 118 Governing Board, 118, 135 Graft, 118, 120, 122 Gram-negative, 118, 129
Granule, 14, 34, 119, 139 Granulosa Cells, 19, 119 Growth, 96, 98, 99, 100, 105, 116, 117, 119, 134, 140, 146 Guanidine, 51, 119 H Habituation, 15, 48, 119 Hallucinogen, 119, 126 Haploid, 119, 134 Haptens, 53, 96, 119 Headache, 59, 60, 92, 119, 120 Headache Disorders, 119 Heart attack, 105, 119 Heme, 82, 110, 119, 134, 135 Hemodialysis, 104, 119, 124 Hemoglobin, 98, 115, 119, 135 Hemorrhage, 11, 109, 119, 142 Heparin, 4, 119 Hepatic, 110, 120, 134 Hepatocytes, 30, 120 Herbicide, 53, 120 Hereditary, 55, 106, 118, 120, 129 Heredity, 117, 120 Heterogeneity, 96, 120 Hexobarbital, 50, 120 Histamine, 100, 107, 116, 120 Histology, 5, 120 Homogeneous, 47, 120 Homologous, 120, 143 Hormone, 102, 109, 114, 120, 136, 140, 141, 144 Host, 42, 101, 120, 122, 147 Hybrid, 15, 120 Hydration, 104, 120 Hydrobromic Acid, 45, 120 Hydrocephalus, 120, 123 Hydrochloric Acid, 45, 47, 120 Hydrogen, 31, 44, 57, 95, 97, 102, 104, 111, 115, 120, 121, 125, 128, 131, 133, 136 Hydrogen Peroxide, 31, 121, 125 Hydrolysis, 100, 121, 134, 136, 139 Hydrophobic, 17, 121 Hydroxides, 45, 121 Hydroxyl Radical, 21, 121 Hydroxylysine, 108, 121 Hydroxyproline, 108, 121 Hyperkalaemia, 24, 121 Hyperkinesia, 59, 60, 121 Hypersecretion, 59, 60, 121 Hypersensitivity, 97, 111, 121 Hypertension, 59, 60, 105, 121, 123 Hyperuricemia, 56, 118, 121
154
Barbiturates
Hyperventilation, 5, 121 Hypnotic, 7, 10, 52, 60, 61, 101, 115, 120, 121, 125, 128 Hypotension, 100, 109, 121 Hypothalamus, 101, 121 Hypothermia, 11, 20, 23, 121 Hypoxia, 49, 54, 110, 121 I Id, 32, 35, 83, 88, 90, 121 Idiopathic, 121, 137 Imaging procedures, 121, 145 Immune response, 95, 99, 109, 119, 122, 147 Immune system, 113, 122, 126, 129, 148 Immunity, 96, 122 Immunoassay, 43, 47, 48, 54, 122 Immunogenic, 46, 47, 122 Immunoglobulin, 99, 122, 128 Immunologic, 122 Immunology, 95, 96, 122 Immunosuppressant, 4, 96, 116, 122 Immunotherapy, 111, 122 Impairment, 110, 113, 122, 127, 137 In vitro, 7, 22, 23, 122 In vivo, 120, 122, 128 Incontinence, 120, 122, 140 Incubated, 46, 122 Incubation, 46, 122 Indicative, 54, 63, 122, 132, 147 Induction, 100, 115, 122, 124, 127 Infarction, 59, 100, 106, 109, 122, 127 Infection, 4, 110, 117, 122, 125, 126, 132, 142, 148 Infiltration, 57, 123 Inflammation, 57, 99, 108, 116, 117, 123, 142, 146 Inflammatory bowel disease, 59, 60, 123 Ingestion, 123, 127, 134 Inhalation, 15, 96, 114, 123, 124, 134 Initiation, 8, 123 Inositol, 15, 123, 140 Insight, 6, 123 Insomnia, 10, 35, 36, 123, 146 Intermittent, 15, 123 Interstitial, 5, 116, 123, 139 Intestinal, 58, 123 Intestine, 103, 123, 125 Intoxication, 91, 110, 123, 148 Intracellular, 14, 122, 123, 135, 138, 140, 141 Intracranial Aneurysm, 11, 123
Intracranial Hypertension, 5, 18, 23, 119, 120, 123 Intracranial Pressure, 20, 22, 23, 123, 136 Intraoperative Period, 11, 123 Intravenous, 9, 21, 26, 123, 127 Intravenous Anesthetics, 9, 123 Intrinsic, 96, 123 Intubation, 21, 105, 123 Involuntary, 101, 106, 123, 129 Ion Channels, 7, 13, 16, 123, 130, 143 Ions, 7, 55, 102, 104, 112, 113, 119, 121, 124, 128, 135 Irritable Bowel Syndrome, 59, 60, 124 Ischemia, 5, 49, 54, 59, 124, 130 Isoflurane, 9, 56, 124 Isopropyl, 43, 47, 124 J Jet lag, 59, 60, 124 K Kb, 76, 124 Ketamine, 23, 64, 124 Keto, 44, 124 Ketone Bodies, 95, 124 Kidney Disease, 4, 76, 124 Kidney Failure, 114, 124, 126 Kidney stone, 124, 146 Kinetic, 14, 16, 124 L Labile, 14, 108, 124 Lag, 124 Lanthanum, 14, 124 Large Intestine, 112, 123, 125, 138, 141 Latency, 20, 125 Lavage, 92, 125 Lesion, 125, 144 Leucocyte, 97, 125 Leukocytes, 103, 125 Levorphanol, 111, 125 Library Services, 88, 125 Ligands, 54, 125, 138 Linkage, 42, 125 Lipid, 21, 106, 118, 124, 125, 128 Lipid Peroxidation, 21, 125 Liquor, 47, 125 Lithium, 100, 125 Liver, 4, 31, 82, 95, 102, 118, 120, 125, 135, 146 Liver Transplantation, 4, 125 Localized, 122, 125, 134 Locomotion, 11, 125, 134 Lorazepam, 8, 125 Lymph, 57, 107, 114, 125, 126
Index 155
Lymph node, 57, 125, 126 Lymphatic, 122, 125, 126 Lymphatic system, 125, 126 Lymphocyte, 57, 99, 126 Lymphoid, 57, 99, 125, 126 Lysergic acid, 25, 126 Lysergic Acid Diethylamide, 25, 126 M Maintenance therapy, 4, 126 Manic, 100, 102, 125, 126, 137 Manic-depressive psychosis, 126, 137 Mannitol, 5, 11, 23, 126 Matrix metalloproteinase, 26, 126 Medetomidine, 34, 111, 126 Medial, 107, 126 Mediate, 16, 107, 112, 126 MEDLINE, 77, 126 Medullary, 111, 126 Megaloblastic, 111, 126 Meiosis, 126, 143, 146 Membrane, 9, 21, 105, 108, 111, 115, 118, 123, 127, 128, 129, 131, 132, 133, 141, 143, 144 Membrane Glycoproteins, 127 Memory, 33, 92, 97, 98, 110, 111, 127 Meninges, 105, 109, 127 Menstrual Cycle, 127, 136 Mental deficiency, 116, 127 Mental Disorders, 127, 136, 137 Mental Health, iv, 5, 76, 78, 127, 137 Mephobarbital, 48, 127 Mesenteric, 57, 127 Mesentery, 127 Mesolimbic, 100, 127 Metabolic disorder, 118, 127 Metabolite, 112, 127 Metaplasia, 56, 127 Metastasis, 126, 127 Methanol, 44, 46, 127 Methionine, 112, 127 Methohexital, 8, 127 MI, 24, 93, 127 Microbe, 127, 145 Microdialysis, 5, 128 Microorganism, 108, 128, 132, 147 Midazolam, 21, 128 Migration, 57, 128 Milliliter, 46, 128 Mineralization, 104, 128 Mobility, 9, 128 Modeling, 26, 128 Modification, 7, 9, 117, 128
Modulator, 6, 128 Molecular Structure, 16, 128, 146 Molecule, 55, 57, 99, 102, 103, 108, 112, 113, 118, 121, 128, 131, 133, 138, 141, 147 Monitor, 48, 128 Monoamine, 39, 97, 99, 111, 128 Monoclonal, 4, 128 Mood Disorders, 4, 128 Morale, 50, 128 Morphine, 4, 103, 107, 128, 129, 131 Morphogenesis, 116, 128 Morphological, 96, 129 Motion Sickness, 129, 140 Motor nerve, 129 Movement Disorders, 100, 129 Mucins, 129, 139 Mucus, 129, 146 Muscarinic Agonists, 106, 129 Muscle relaxant, 61, 99, 129 Muscle tension, 129 Mutagenesis, 7, 16, 129 Mutagens, 129 Myasthenia, 119, 129 Mycoplasma, 21, 105, 129 Mydriatic, 129, 140 Myocardium, 64, 127, 129 N Naive, 11, 129 Narcosis, 129 Narcotic, 49, 116, 125, 128, 129, 131 Nausea, 59, 60, 99, 100, 117, 129, 132, 136, 146 Necrosis, 103, 106, 122, 127, 129 Need, 3, 4, 43, 48, 52, 56, 64, 84, 107, 118, 126, 130, 145 Nephropathy, 124, 130 Nerve, 49, 55, 96, 98, 107, 111, 114, 129, 130, 135, 136, 139, 142, 146, 147 Nervous System, 6, 9, 48, 63, 95, 96, 97, 101, 102, 105, 107, 111, 117, 118, 126, 128, 130, 133, 140, 143, 144 Neuroleptic, 96, 100, 130 Neurologic, 4, 11, 59, 99, 120, 130 Neurology, 12, 13, 18, 23, 30, 49, 55, 130 Neuromuscular, 95, 130 Neuromuscular Junction, 95, 130 Neuronal, 5, 8, 13, 14, 30, 59, 60, 129, 130 Neurons, 12, 13, 14, 21, 49, 55, 59, 106, 107, 111, 115, 117, 129, 130, 143 Neuropharmacology, 24, 31, 55, 130 Neurophysiology, 12, 111, 130 Neuroprotective Agents, 58, 130
156
Barbiturates
Neurotoxic, 49, 55, 59, 130 Neurotoxicity, 111, 130 Neurotransmitters, 59, 115, 130, 141 Nickel, 44, 130 Nicotine, 59, 60, 64, 130 Nitrogen, 96, 97, 115, 131, 146 Nitrous Oxide, 10, 34, 56, 131 Nuclei, 107, 113, 117, 131, 136 Nucleus, 52, 101, 107, 110, 111, 127, 131, 136, 141 O Odour, 100, 131 Oliguria, 124, 126, 131 Oocytes, 12, 13, 131 Opacity, 111, 131 Opium, 128, 131 Oral Health, 64, 131 Oral Hygiene, 4, 131 Oral Manifestations, 4, 131 Organelles, 110, 131, 132 Orthostatic, 100, 131 Osmolarity, 126, 131 Outpatient, 4, 131 Ovarian Follicle, 109, 119, 131 Overdose, 22, 48, 58, 91, 131 Ovulation, 119, 131 Ovum, 109, 118, 131, 136 Oxidation, 95, 110, 125, 131 P Palladium, 44, 132, 139 Palliative, 132, 144 Palsy, 59, 60, 132 Panic, 6, 59, 60, 132 Panic Disorder, 6, 59, 60, 132 Paralysis, 110, 132, 141 Paresthesias, 132 Parkinsonism, 100, 132 Particle, 45, 132, 145 Patch, 6, 9, 13, 16, 132 Patch-Clamp Techniques, 9, 132 Pathogen, 122, 132 Pathologic, 95, 109, 121, 132 Patient Education, 82, 86, 88, 93, 132 Penicillin, 14, 99, 132 Peptide, 114, 132, 134, 136 Perfusion, 5, 20, 117, 121, 132 Perinatal, 49, 133 Peripheral Nervous System, 132, 133 Peripheral Vascular Disease, 116, 133 PH, 58, 133 Pharmacodynamics, 4, 133 Pharmacologic, 4, 56, 97, 98, 133, 145
Phenobarbital, 37, 43, 48, 50, 70, 127, 133 Phenyl, 43, 56, 133 Phospholipids, 116, 123, 133 Phosphorus, 104, 133 Phosphorylase, 42, 133 Phosphorylation, 7, 133 Physiologic, 96, 102, 127, 133, 138 Physiology, 3, 13, 16, 95, 113, 130, 133, 147 Picrotoxin, 14, 134 Pipette, 47, 134 Placenta, 134, 136 Plants, 53, 54, 96, 101, 102, 104, 106, 107, 118, 120, 134, 145, 146 Plasma, 25, 96, 99, 105, 117, 118, 119, 124, 129, 134 Plasma cells, 99, 134 Plasticity, 7, 134 Platinum, 44, 132, 134, 139 Poisoning, 26, 49, 54, 110, 115, 117, 123, 129, 134 Polymerase, 100, 134 Polymers, 42, 134, 136, 142 Polypeptide, 48, 97, 108, 134, 148 Polysaccharide, 99, 105, 134 Polystyrenes, 45, 134 Porphyria, 82, 134 Porphyrins, 134 Posterior, 106, 112, 135 Postnatal, 116, 135 Postoperative, 4, 11, 135 Postsynaptic, 6, 9, 11, 12, 30, 135, 141, 143 Post-synaptic, 9, 13, 135 Potassium, 11, 13, 45, 121, 135 Potassium Channels, 13, 135 Potassium hydroxide, 45, 135 Potentiate, 9, 22, 30, 135 Potentiating, 9, 10, 34, 42, 52, 135 Practice Guidelines, 78, 135 Precipitation, 15, 135 Preclinical, 15, 135 Precursor, 106, 112, 113, 114, 135, 146 Prednisolone, 135 Prednisone, 4, 135 Premedication, 135, 140 Prenatal, 116, 135 Presynaptic, 9, 135, 143, 144 Probe, 12, 119, 128, 135 Progesterone, 19, 136 Progression, 98, 136 Progressive, 59, 60, 107, 111, 113, 119, 129, 136, 139 Proline, 24, 108, 121, 136
Index 157
Prophase, 131, 136, 143, 146 Prophylaxis, 100, 116, 136 Propofol, 4, 9, 14, 23, 27, 56, 136 Protease, 15, 136 Protease Inhibitors, 15, 136 Protein C, 13, 14, 97, 101, 136, 146 Protein S, 100, 102, 136, 139 Proteolytic, 97, 108, 136 Protons, 121, 136, 138 Proximal, 112, 135, 136 Pruritus, 100, 136 Pseudotumor Cerebri, 123, 136 Psychiatric, 4, 6, 127, 136 Psychiatry, 8, 136, 142, 147 Psychic, 136, 137, 140 Psychomotor, 15, 110, 130, 137 Psychosis, 59, 60, 100, 137 Psychotomimetic, 97, 111, 137 Psychotropic, 21, 137 Psychotropic Drugs, 21, 137 Public Health, 15, 50, 78, 137 Public Policy, 77, 137 Publishing, 16, 137 Pulmonary, 102, 106, 109, 117, 121, 124, 137, 147 Pulmonary Artery, 102, 137, 147 Pulmonary Edema, 106, 124, 137 Pulmonary Ventilation, 121, 137 Pulse, 92, 114, 128, 137 Purines, 137, 140 Purulent, 137 Pyoderma, 59, 60, 137 Pyoderma Gangrenosum, 59, 60, 137 Pyridoxal, 49, 138 Q Quaternary, 138, 140 Quiescent, 6, 138 R Race, 111, 128, 138 Radiation, 116, 138 Radioactive, 12, 52, 121, 138 Radioisotope, 138, 145 Randomized, 11, 113, 138 Randomized clinical trial, 11, 138 Reagent, 9, 43, 53, 106, 117, 120, 138 Reality Testing, 137, 138 Receptor, 6, 7, 8, 10, 12, 13, 16, 17, 24, 25, 30, 31, 48, 50, 54, 55, 56, 58, 60, 95, 99, 103, 106, 107, 111, 112, 116, 133, 138, 140, 141 Receptors, Adrenergic, 111, 126, 138 Recombinant, 7, 13, 14, 25, 138, 147
Rectum, 112, 116, 117, 122, 123, 125, 138 Recurrence, 102, 126, 138 Red blood cells, 27, 115, 138 Refer, 1, 108, 112, 125, 129, 130, 137, 138 Reflux, 45, 47, 138 Refractory, 20, 138 Regimen, 113, 138 Relaxant, 138 Remission, 102, 126, 138, 139 Renal failure, 4, 110, 139 Respiration, 92, 104, 106, 110, 128, 139 Response rate, 8, 139 Retinoid, 50, 139 Ribose, 95, 139, 146 Ribosome, 139, 145 Rigidity, 123, 132, 134, 139 Rod, 107, 139 Rubber, 13, 95, 139 Ruthenium, 44, 139 S Saline, 23, 139 Saliva, 45, 54, 139 Salivary, 139 Salivary glands, 139 Saponification, 44, 139 Schizoid, 139, 148 Schizophrenia, 8, 59, 60, 100, 139, 148 Schizotypal Personality Disorder, 111, 139, 148 Sclerosis, 59, 60, 139 Scopolamine, 55, 140 Screening, 15, 17, 24, 25, 48, 65, 107, 140 Secobarbital, 46, 48, 55, 140 Second Messenger Systems, 130, 140 Secretion, 120, 121, 129, 140 Secretory, 140, 143 Sedative, 7, 10, 59, 61, 101, 106, 107, 111, 116, 120, 125, 126, 128, 140 Seizures, 48, 110, 140, 142 Senile, 60, 100, 140 Sensibility, 98, 140 Serine, 50, 114, 140 Serologic, 122, 140 Serotonin, 100, 103, 126, 140, 146 Serum, 17, 18, 20, 24, 30, 36, 45, 47, 48, 56, 100, 108, 140 Shock, 140, 146 Side effect, 4, 49, 55, 57, 60, 69, 96, 100, 121, 124, 125, 140, 145 Signal Transduction, 123, 141 Skeletal, 107, 110, 141 Skull, 109, 110, 123, 141
158
Barbiturates
Sleep apnea, 141, 142 Small intestine, 30, 113, 120, 123, 141 Smooth muscle, 97, 120, 128, 129, 141 Sodium, 31, 45, 47, 53, 55, 56, 118, 141 Soft tissue, 103, 141 Solitary Nucleus, 101, 141 Solvent, 13, 15, 44, 95, 102, 115, 118, 127, 141 Sorbitol, 126, 141 Spastic, 59, 60, 124, 141 Spasticity, 101, 141 Specialist, 83, 142 Species, 58, 110, 114, 117, 120, 127, 128, 138, 142, 143, 146, 147, 148 Specificity, 52, 54, 96, 114, 142 Spinal cord, 101, 103, 105, 114, 127, 130, 133, 142, 143 Sprue, 59, 60, 142 Stabilization, 6, 142 Status Epilepticus, 20, 142 Steel, 107, 142 Steroids, 7, 11, 12, 50, 53, 118, 142 Stimulant, 97, 111, 120, 134, 142 Stimulus, 113, 123, 124, 125, 132, 142, 144 Stomach, 60, 95, 112, 115, 117, 120, 125, 129, 138, 141, 142 Stool, 122, 124, 125, 142 Stress, 6, 30, 101, 117, 124, 129, 139, 142 Stroke, 18, 49, 54, 55, 59, 60, 76, 105, 130, 142 Strychnine, 6, 142 Stupor, 129, 142 Styrene, 45, 134, 139, 142 Subacute, 122, 142 Subarachnoid, 11, 119, 142 Subclinical, 122, 140, 142 Subcutaneous, 113, 143 Subspecies, 142, 143 Substrate, 26, 143 Suction, 116, 132, 143 Sulfuric acid, 45, 143 Suppression, 18, 20, 31, 111, 143 Supraspinal, 101, 143 Sympathetic Nervous System, 101, 143 Sympathomimetic, 97, 111, 112, 114, 143 Symptomatic, 99, 106, 143 Symptomatic treatment, 99, 106, 143 Synapses, 9, 55, 130, 143, 144 Synapsis, 143 Synaptic, 6, 8, 14, 16, 55, 130, 141, 143, 144 Synaptic Transmission, 130, 143 Synaptic Vesicles, 143, 144
Synergistic, 5, 56, 144 Systemic, 70, 102, 110, 114, 122, 123, 135, 144 Systolic, 121, 144 T Tardive, 59, 60, 100, 144 Taurine, 50, 144 Testosterone, 98, 144 Tetrahydrocannabinol, 104, 144 Theophylline, 56, 97, 137, 144 Therapeutics, 71, 144 Thiamine, 49, 144 Thiobarbiturates, 26, 51, 144 Thiourea, 53, 144 Threonine, 140, 144 Threshold, 59, 115, 121, 144 Thrombin, 136, 144 Thrombomodulin, 136, 144 Thrombosis, 136, 142, 144 Thrombus, 109, 122, 145 Tidal Volume, 121, 145 Tin, 134, 145 Tissue, 42, 50, 51, 57, 58, 60, 96, 98, 99, 102, 103, 104, 109, 113, 114, 115, 118, 121, 123, 125, 126, 127, 129, 130, 131, 132, 139, 140, 141, 142, 145, 146, 148 Tolerance, 7, 10, 15, 95, 103, 145 Tonic, 6, 145 Tonicity, 113, 145 Topical, 115, 121, 145 Torsion, 122, 145 Toxic, iv, 42, 49, 51, 96, 101, 102, 110, 122, 127, 130, 135, 142, 145 Toxicity, 34, 42, 112, 145 Toxicology, 17, 23, 24, 31, 34, 78, 145 Toxins, 99, 114, 118, 122, 145 Trace element, 130, 145 Tracer, 47, 145 Traction, 107, 145 Tranquilizing Agents, 137, 145 Transduction, 9, 141, 145 Transfection, 102, 145 Translation, 6, 145 Transmitter, 95, 112, 115, 123, 143, 144, 146 Transplantation, 107, 146 Trauma, 23, 55, 59, 110, 130, 146 Trees, 139, 146 Triazolam, 8, 146 Tricyclic, 4, 99, 146 Trigger zone, 100, 146 Tryptophan, 108, 140, 146
Index 159
Tuberculosis, 109, 146 U Ulcerative colitis, 59, 60, 123, 137, 146 Unconscious, 98, 121, 146 Univalent, 121, 132, 146 Uracil, 42, 146 Urea, 48, 146 Uremia, 124, 139, 146 Urethra, 146 Uric, 55, 118, 121, 137, 146 Uridine Phosphorylase, 42, 146 Urinary, 104, 120, 122, 129, 131, 140, 146, 148 Urine, 18, 21, 22, 24, 45, 54, 102, 112, 114, 119, 122, 124, 131, 146 Uterus, 109, 136, 146 V Vascular, 25, 97, 119, 122, 131, 134, 145, 147 Vasoconstriction, 59, 60, 114, 147 Vasodilators, 52, 147 Vector, 145, 147 Vein, 98, 123, 147 Venous, 103, 106, 136, 147 Venous blood, 103, 106, 147 Ventilation, 115, 147 Ventral, 107, 121, 147
Ventricle, 121, 137, 144, 147 Venules, 57, 103, 104, 147 Vertigo, 116, 147 Vesicular, 119, 147 Veterinary Medicine, 77, 126, 147 Viral, 4, 42, 100, 145, 147 Virulence, 145, 147 Virus, 100, 101, 105, 117, 145, 147 Virus Diseases, 100, 147 Visceral, 101, 147 Visceral Afferents, 101, 147 Vitamin A, 123, 139, 147 Vitro, 30, 120, 147 Vomica, 142, 148 W Wakefulness, 34, 110, 148 White blood cell, 99, 122, 125, 126, 129, 134, 148 Withdrawal, 10, 24, 26, 30, 31, 48, 49, 64, 66, 110, 148 Wound Healing, 126, 148 X Xanthine, 56, 148 Xenograft, 98, 148 Z Zymogen, 136, 148
160
Barbiturates
