A comprehensive, state-of-the-art review of our current understanding of the molecular and structural biology of 5-HT receptors and their potential use for drug discovery. The authors describe the anatomical, cellular, and subcellular distribution of 5-HT receptors and demonstrate a powerful approach to elucidating their physiological role using knockout mice in which the 5-HT receptors were deleted. They also review our understanding of the physiological role(s) of 5-HT receptors based mainly on studies performed in genetically engineered mice. Highlights include discussions of the behavioral phenotypes of 5-HT receptor knockout animals, the molecular biology and pharmacology of 5-HT receptors, and insights into the complexity of 5-HT receptor signal transduction.

The three years since our last conference in San Francisco have again seen a dramatic expansion of the number of antivirals either licensed or in the late stages of clinical trials. d4T is now licensed for HIV infection, famciclovir and the oral pro-drug of acyclovir, valacyclovir, are now licensed for VZV infections in some countries. Moreover. oral ganciclovir, cidofovir, and sorivudine are not far behind. Clinical trials with the second-site reverse transcriptase inhibitors and the protease inhibitors for HlV infection are proceeding rapidly and on a broad scale, and the preliminary results would suggest that several of these classes of drugs will be licensed as well. Despite this optimism, however, there is increasing evidence that antiviral-resistant strains of pathogenic viruses will be a significant problem, perhaps especially with therapy of HIV infection, and there remains a desperate need for improved drugs (with either improved efficacy or decreased toxicity, or both) for CMV and HIV infections. This book is the edited proceedings of the Fourth Triennial Conference on Antiviral Chemotherapy, held in San Francisco, in November 1994. The conference was sponsored by the University of California, San Francisco, and co-sponsored by the International Society for Antiviral Research (ISAR), the Macfarlane Burnet Centre for Medical Research in Melbourne, Australia, and the Australian National Centre for HIV Virology Research. The conference had been organized to present an overview of the field of antiviral chemotherapy.

After the discovery of endogenous NO formation in the late '80s and the 1998 Nobel Prize in Physiology or Medicine, many researchers and physicians again became interested in the NO/sGC interaction and cGMP-dependent signaling. This book is an enthusiastic celebration of cyclic guanosine monophosphate (cGMP) and amply illustrates the importance of this field of science to patients and the way in which the field has evolved. It is exclusively devoted to this exciting and important signaling molecule, addressing all recent advances in understanding guanylate cyclase regulation, NO/sGC interactions, cGMP effector mechanisms and their pathophysiological and pharmacological implications. Particular attention will also be given to clinical applications of the novel cGMP-elevating drugs which are on the horizon, thus spanning the continuum from basic science to clinic.

As the drug discovery process shifts more and more toward specifically targeting pathways and molecules, model systems continue to increase in importance, and the mouse, with its versatility, ease of use, and remarkable similarity to the human genome, has clearly risen to the forefront of animal model studies. In Mouse Models for Drug Discovery: Methods and Protocols, experts in the field present some background for those less familiar with mice as experimental model platforms as well as a collection of techniques involving general methods as well as specific disease topics such as type 1 and 2 diabetes, cardiovascular disease, arthritis, skin disorders, cancer, the use of behavioral models for depression and anxiety, neurodegenerative diseases, neuromuscular diseases, and infectious diseases. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and notes on troubleshooting and avoiding known pitfalls.

Authoritative and easy-to-use, Mouse Models for Drug Discovery: Methods and Protocols will stimulate those not familiar with the power of the mouse and its potential for the drug discovery process, and it will encourage the development of new models and new ways to utilize existing models in order to further the use of this dynamic animal in this vital field."

This book provides the most up-to-date review of the simian virus 40 (SV40) minichromosome as a model for the mammalian chromosome in studies of DNA replication. It focuses on disruption of DNA replication by anticancer drugs and DNA-damaging agents. There is a strong emphasis on the unique advantages of SV40 as an experimental system for the analysis of these classes of anticancer drug mechanisms. The new high-resolution gel electrophoresis methods for the analysis of SV40 DNA replication are covered in detail to aid readers in designing and interpreting similar experiments.
Key Features
* Presents unique advantages of SV40 as an experimental system for the study of classes of anticancer drugs
* Details new high-resolution gel electrophoresis methods for the analysis of SV40 DNA replication
* Provides details to help the reader design and interpret similar experiments

Genetic Algorithms in Molecular Modeling is the first book available on the use of genetic algorithms in molecular design. This volume marks the beginning of an ew series of books, Principles in Qsar and Drug Design, which will be an indispensible reference for students and professionals involved in medicinal chemistry, pharmacology, (eco)toxicology, and agrochemistry. Each comprehensive chapter is written by a distinguished researcher in the field.
Through its up to the minute content, extensive bibliography, and essential information on software availability, this book leads the reader from the theoretical aspects to the practical applications. It enables the uninitiated reader to apply genetic algorithms for modeling the biological activities and properties of chemicals, and provides the trained scientist with the most up to date information on the topic.
. Extremely topical and timely
. Sets the foundations for the development of
computer-aided tools for solving numerous
problems in QSAR and drug design
. Written to be accessible without prior direct
experience in genetic algorithms

380 years ago, in the year 1614, Ubbo Emmius transplanted the gene ofscience from Ostfriesland into the education genome ofthe city ofGroningen as devel oped by Regnerus Praedinius. He thereby founded the University ofGroningen. It is with great pleasure that the Faculty of Medicine as one of the founding faculties ofour University, welcomes you to this 19th International Symposium ofBloodTransfusion, whichwill coverthe themeofHereditaryDiseasesandtheir relation to Transfusion Medicine, where cell expansion, gene transfer and gene therapy are the read thread. Since the earlydays there has beena specificand sincere interest in inborn errors ofmetabolism and hereditarydisorders. This interest has resulted in a structured research, diagnostic and counselling facilities, and therapeuticapproaches where various disciplines within our faculty work closely together with groups from related faculties of the University of Groningen, as well as other national and international scientific institutions. The field of inborn errors, genetic abnormalities and mutations, and hereditary diseases covers a broad gamma of extremely interesting and exciting scientific aspects, whichrangefrom clearphysicalaberrationstomolecularanalysisofgenes and genomes, coding areas and amino acid sequences. It is intriguing to realise that the balance of life seemingly depends on the position or presence of one single molecule as a part ofthe total complex ofgenetic information in the cell."

Over the past ten years, a number of cytokines and growth factors have proven to be as effective therapeutics. While these products have certainly established recombinant biologics as a major pharmaceutical growth sector, the continued interest in this class of drugs arises from the fact that today we have a far better understanding of the human immune response, both at a cellular and molecular level. This has resulted in a more methodical characterisation of these factors which has given clinical researchers an opportunity to plan Phase 1 clinical trials that can provide substantial information on the activity of the cytokine in humans. Currently, a great deal of effort is also being channelled into identifying cytokines from the various DNA databases. Our major objective for this book is to profile cytokines that have been recently identified. The therapeutic potential of these cytokines based on their known properties will be discussed by the authors. The main aim of this book is to provide...

Covering ocular pharmacokinetics, pharmacodynamics, and toxicology, Ocular Pharmacology and Toxicology provides ophthalmologists, toxicologists, and pharmacologists with both an introduction to the proper methods for ocular pharmacology and toxicology as well as providing practical methodologies for conducting ocular studies. Expert authors have contributed detailed chapters on study design, analysis, and routes to regulatory approval for various types and routes of ophthalmic drugs. As a volume in the Methods in Pharmacology and Toxicology series, chapters feature the kind of in-depth specifics and implementation advice to ensure successful results. Practical and authoritative, Ocular Pharmacology and Toxicology serves as an ideal basis of training in the proper design and conduct of essential studies to accurately determine pharmacokinetics and ocular toxicity from the systemic, topical, periocular, or intraocular administration of drugs or compounds, from the use of ocular medical devices and from ocular surgical procedures.

The present volume gives a comprehensive overview on the current state of basic and clinical research on Anxiety and Anxiolytic Drugs. Using newly developed methods and techniques researchers are now beginning to understand the molecular mechanisms of anxiety, anxiety disorders and their treatment. In parallel, new drug targets have been generated and the first clinical studies with new compounds have been started. In 20 chapters written by numerous experts in the field comprehensive information on all relevant topics is provided.

Drinking alcohol can, in rare instances, provoke a temporary psychotic often violent reaction called pathological intoxication. Although it was medically identified in 1869, pathological intoxication has been an enigma to the law for over a century, primarily because the actual medical and psychiatric aspects of the concept have not been adequately explained before. But, as the authors of this volume point out, it is crucial for the defense attorney and the prosecutor to understand whether pathological or ordinary intoxication is involved in a particular case because pathological intoxication furnishes the basis of important and perhaps decisive defense strategies beyond those which derive from ordinary intoxication. This interdisciplinary study provides the first in-depth exploration of both the medical and psychiatric facts underlying the phenomenon of pathological intoxication and explores the suitability of various defense theories.

Written especially for practicing criminal defense lawyers, public defenders, prosecutors, and forensic psychiatrists, the volume begins by examining the clinical and experimental evidence of pathological intoxication. In subsequent chapters, the authors alert the attorney to the indications that a defendant should be examined for possible pathological intoxication and include hard-to-find medical sources of support for the concept to persuade courts and prosecutors of its legitimacy. A series of chapters thoroughly explores all the relevant legal defense strategies available in pathological intoxication cases including the defense of automatism, the law of insanity, involuntary intoxication, and diminished capacity and extreme mental and emotional disturbance. Throughout, the authors incorporate both domestic and foreign literature relating to pathological intoxication. The inclusion of ample case examples as well as a wealth of medical and psychiatric data make this book a major contribution to our understanding of both the phenomenon of pathological intoxication and its implications for legal defense strategy.

Untoward reactions to environmental chemicals, particularly when a subject reports difficulties with exposures to chemicals of diverse classes involving more than one organ system, have been poorly understood and an area of great controversy. Studies of airway inflammation induced by respiratory irritants have established neurogenic inflammation as the mechanism for irritant asthma and rhinitis. Remodeling of the airway after an acute irritant exposure can lead to a heightened sensitivity to irritants that persists. Recognition that rhinitis, while sometimes regarded as a trivial disease, is associated with extra-airway manifestations such as fatigue and disturbances of sleep, mood, and cognition, further elucidates how chemical exposures can be serious for susceptible individuals.
This book reviews current scientific understanding of irritant airway inflammation and related conditions, including cardiovascular effects of particulate exposures, airborne contact dermatitis and irritant dermatitis, and the brain as a target organ for both allergic and irritant reactions. It is essential reading for physicians and other healthcare workers caring for patients with environmental intolerances. Allergists, toxicologists, occupational and environmental physicians, and pulmonologists will find the materials particularly valuable. Patients and advocates for those with chemical intolerances will also find the book of interest.

Medicinal chemistry is both science and art. The science of medicinal chemistry offers mankind one of its best hopes for improving the quality of life. The art of medicinal chemistry continues to challenge its practitioners with the need for both intuition and experience to discover new drugs. Hence sharing the experience of drug research is uniquely beneficial to the field of medicinal chemistry. Drug research requires interdisciplinary team-work at the interface between chemistry, biology and medicine. Therefore, the topic-related series Topics in Medicinal Chemistry covers all relevant aspects of drug research, e.g. pathobiochemistry of diseases, identification and validation of (emerging) drug targets, structural biology, drugability of targets, drug design approaches, chemogenomics, synthetic chemistry including combinatorial methods, bioorganic chemistry, natural compounds, high-throughput screening, pharmacological in vitro and in vivo investigations, drug-receptor interactions on the molecular level, structure-activity relationships, drug absorption, distribution, metabolism, elimination, toxicology and pharmacogenomics. In general, special volumes are edited by well known guest editors.

The first comprehensive book to cover all aspects of the last 25 years of PACAP (pituitary adenylate cyclase activating polypeptide) research, this book contains contributions from virtually all the leading researchers in the field, and addresses some of the following topics: evolutionary aspects of PACAP, distribution and occurrence of PACAP and its receptors, hormonal effects of PACAP, intracellular signaling, effects on cellular proliferation and differentiation, protective effects of PACAP, behavioral effects of PACAP, developmental aspects of PACAP, other physiological effects of PACAP (cardiovascular, thermoregulatory), human studies, drug design, metabolism and transport. This compendium can serve as an important reference for researchers and students in PACAP research and can also be a thorough introduction for those in related fields.

Neurotoxicology: Approaches and Methods provides a unique and comprehensive presentation of the current concepts and state-of-the-art methods for the assessment of neurotoxicity. The book analyzes various techniques available and discusses their strengths and weaknesses. This volume will serve as an excellent desk companion and laboratory guide for all investigators, researchers, clinicians, and students interested in neurotoxicology. The internationally knowngroup of editors divide the book into seven sections: "Neuromorphological and Neuropathological Approaches; Neurophysiological Approaches; Neurobehavioral Toxicology; Neurochemical and Biomolecular Approaches; In-Vitro Models; Clinical Neurotoxicology; and Risk Assessment of Neurotoxicity." Each section yields the most up-to-date information by experts in their fields. Meticulously organized and edited, Neurotoxicology: Approaches and Methods is the most authoritative and well-planned neurotoxicology book on the market.
Key Features
* Discusses neurobehavioral testing methods for assessment of neural dysfunctions
* Explains state-of-the-art diagnostic methods, such as clinico-neuropsychological and neurophysiological methods, for patients confronted by neurotoxic problems
* Discusses "In Vitro" methods, including aggregating brain cell methods, organotypic cultures, and the use of human neuronal cell lines for the assessment of neurotoxicity
* Presents step-by-step procedures for many methods
* Provides state-of-the-art neuromorphological and biomolecular methods and approaches for neurotoxicity investigation

Chemical genomics is a highly interdisciplinary and very exciting field of research both in academics and in the life sciences industry. The Ernst Schering Research Foundation Workshop 58 was organized to bring together scientific leaders in the field to discuss the implications of chemical genomics for drug discovery. Various aspects of the interface between chemistry and biology are covered in this volume, such as chemogenomics efforts in the pharmaceutical industry, diversity-oriented synthesis, chemogenomic approaches to the study of cell function, screening technologies, and natural products as tools in chemical biology.

Biomedical Science Chinese herbal medicine represents complementary or adjunctive therapies that often can improve the efficacy of Western medicine to achieve the pharmacological effects, especially in cancer treatment. However, the combination of herbs with therapeutic drugs can raise potential health risk. Building a bridge between Western medicine and herbal medicines, Active Phytochemicals from Chinese Herbal Medicines: Anti-Cancer Activities and Mechanisms gives you useful information on how integrated medicines can work for cancer therapy. It discusses the therapeutic uses of phytochemicals, adverse effects, and interactions with (Western) cancer drugs. The author takes a unique approach to integrated pharmacology of herbal medicines, examining the development of phytochemicals and their mechanisms of action in the context of the cancers and diseases they are used to treat. He covers biologic action of the active phytochemicals at the molecular, cellular, and organ levels. The book covers the principles of the interaction of phytochemicals and the related drug actions. It also addresses the common pathways affecting cancer development before discussing the phytochemical classes and specific phytochemicals that have been recently reported in journal papers for the management of cancer and other diseases. Highlighting the increasingly important aspects of pharmacology, including health benefit and drawbacks of phytochemicals, the book presents the relevant background of the biochemistry of the cancer. It includes illustrations and tables with adverse reactions that highlight important issues related to phytochemical actions. These features and more make the book a useful reference on phytochemicals obtained from herbal medicines. It blends coverage of fundamental mechanisms of anti-cancer action and the use of phytochemicals to manage cancers and other human diseases, allowing you to explore how herbal medicines can enhance conventional protocols.

A mother's narcotics abuse can have profound effects on her pregnancy and the health of her child, both inside and outside the womb. Spontaneous abortion, premature birth, labor difficulties, increased perinatal and neonatal mortality, respiratory distress, low birth weight, and passed on addiction are just some of the possibilities. Ernest Abel's Narcotics and Reproduction: A Bibliography is the first comprehensive listing of the scholarly research literature produced on this subject. Arranged alphabetically by author, the book lists materials dealing with the effects of the use of heroin, morphine, methadone, and related drugs on sexual function, reproduction, and the fetus.

Over the past 50 years a wide variety of antibacterial substances have been discovered and synthesised, and their use in treating bacterial infection has been spectacularly successful. Today there are several general classes of antibacterial drugs, each having a well established set of uses, and together they form the mainstay of modern antibacterial chemotherapy. In search for new and improved agents, the pharmaceutical researcher needs to be well informed on many topics, including existing agents, their modes of action and pharmacology, and possible synthetic approaches. In this new book the author has brought together a wide range of information on the principal classes of antibacterial agents, and he covers, for each group, their history, mode of action, key structural features, synthesis and bacterial resistance. The result is a compact and concise overview of these very important classes of antibacterial agents.

Foreword Barry Jacobs once memorably commented that the problem in understanding the role of serotonin in the brain was that it was implicated in virtually eve- thing but responsible for nothing 1]. Serotonin (5-HT) is defnitely implicated in the regulation of sleep but what does it do? Once seen as a sleep-promoting molecule, Jacob s own work, lucidly described in this volume, radically changed our view. In fact, serotonin neurons are most active during waking; their - tivity diminishes with sleep onset and disappears during rapid eye movement (REM) sleep. Serotonin, therefore, is intimately linked to the sleep-wake cycle, but what is its role, what mechanisms are involved and what are the impli- tions for sleep medicine and psychiatry? Making progress with these diffcult questions requires a translational approach, which is a research paradigm where both laboratory and clinical neuroscience inform and guide each other with the ultimate aim of improving understanding and treatment of medical conditions. This volume is a superb example of translational research, where leading basic and clinical scientists - tegrate molecular, neuropharmacological and systems approaches to illuminate the reciprocal interactions of serotonin neurons and the mechanisms involved in sleep and circadian regulation. Serotonin is an ancient chemical mediator preserved through at least 500 m- lion years of evolution. In invertebrate animals such as mollusks and leeches, 5-HT cells are distributed throughout the nervous system among the various ganglia."

An extraordinary compendium of information on herbal medicine, Medicinal Plants of the World, Volume 2 comprehensively documents the medicinal value of twenty-four major plants species widely used around the world in medical formulations. The book's exhaustive summary of available scientific data for the plants provides detailed information on how each plant is used in different countries, describing both traditional therapeutic applications and what is known from its use in clinical trials. A comprehensive bibliography of over 3000 references cites the literature available from a wide range of disciplines. This book offers an unprecedented collection of vital scientific information for pharmacologists, herbal medicine practitioners, drug developers, medicinal chemists, phytochemists, toxicologists, and researchers who want to explore the use of plant materials for medicinal and related purposes.