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.

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.

While systems biology and pharmacodynamics have evolved in parallel, there are significant interrelationships that can enhance drug discovery and enable optimized therapy for each patient. Systems pharmacology is the relatively new discipline that is the interface between these two methods. This book is the first to cover the expertise from systems biology and pharmacodynamics researchers, describing how systems pharmacology may be developed and refined further to show practical applications in drug development. There is a growing awareness that pharmaceutical companies should reduce the high attrition in the pipeline due to insufficient efficacy or toxicity found in proof-of-concept and/or Phase II studies. Systems Pharmacology and Pharmacodynamics discusses the framework for integrating information obtained from understanding physiological/pathological pathways (normal body function system vs. perturbed system due to disease) and pharmacological targets in order to predict clinical efficacy and adverse events through iterations between mathematical modeling and experimentation.

The field of DNA vaccines has undergone explosive growth in the last few years. As usual, some historical precursors of this approach can be d- cerned in the scientific literature of the last decades. However, the present state of affairs appears to date from observations made discreetly in 1988 by Wolff, Malone, Felgner, and colleagues, which were described in a 1989 patent and published in 1990. Quite surprisingly, they showed that genes carried by pure plasmid DNA and injected in a saline solution, hence the epithet "naked DNA," could be taken up and expressed by skeletal muscle cells with a low but reproducible frequency. Such a simple methodology was sure to spawn many applications. In a separate and important line of experimentation, Tang, De Vit, and Johnston announced in 1992 that it was indeed possible to obtain humoral immune responses against proteins encoded by DNA delivered to the skin by a biolistic device, which has colloquially become known as the "gene gun. " The year 1993 saw the publication of further improvements in the me- ods of naked DNA delivery and, above all, the first demonstrations by several groups of the induction of humoral and cytotoxic immune responses to viral antigens expressed from injected plasmid DNA. In some cases, protection against challenge with the pathogen was obtained. The latter result was - questionably the touchstone of a method of vaccination worthy of the name.

Proceedings of the International Symposium on Polymer Therapeutics - Recent Progress in Clinics and Future Prospects, held July 13-14, 2001, in Nara, Japan.

The technology of polymer science has developed considerably during the past half-century, and this volume describes some of the aspects of this technology that will have a great impact in the future. Among these advances, for example, are gene delivery to specific disease sites and carrier polymers that respond to a stimulus or particular environment. Cancer targeted drug delivery is another focused area of this volume because of the important nature of EPR-effect of polymer drugs in tumor. Included are discussions of as many examples as possible of polymer drugs that have achieved, or are close to clinical use. The concept of "Polymer drugs" here is limited to primarily injectable and water-soluble agents, although also covered are some drugs in micellar form or liposomes.

This book is intended for students and researchers in the field of pharmacology who have particular interests in drug delivery, targeting, and formulation, as well as for clinicians such as oncologists who are interested in the field. People who work at regulatory agencies should also be aware such that drugs with great potential are being developed and will be beneficial to many patients, as well as to health insurance agencies because of improved cost effectiveness.

This book contains 55 chapters that summarize referred to the special issue of Drug Development lectures given during the Fifth International Research (Volume 31, Number 4, April 1994). Symposium on Adenosine and Adenine Measured by the number and quality of presenta- Nucleotides held in Philadelphia, Pennsylvania, tions, and by the record number of participants, U. S. A. , May 9-13, 1994. The symposium and the Fifth International Symposium on Adenosine its proceedings follow four previous symposia and Adenine Nucleotides was clearly an intel- and their published proceedings. Previous sym- lectually stimulating meeting. It is safe to posia were held in Banfff, Canada (1978), conclude that the purine research field is vibrant Charlottesville, Virginia (1982), Munich, and still growing. Adenosine has rapidly become Germany (1986), and Lake Yamanaka, Japan the drug of choice for the acute management (1990). of supraventricular tachyarrhythmias and was The program included a wide range of sub- recently approved for use in combination with jects from molecular and cellular biology to cardiac imaging for detection of ischemic heart clinical applications. Great emphasis was placed disease. Additional clinical applications of on cutting edge information derived from studies adenosine and adenosine-related drugs and ATP using molecular and cellular biology techniques seem closer than ever before. The editors would like to express their grati- applied to the field of adenosine and adenine nucleotide research. Likewise, the program tude to the distinguished contributors for their included a number of presentations on poten- excellent chapters and to all participants.

This volume provides state-of-the-art and novel methods on antibiotic isolation and purification, identification of antimicrobial killing mechanisms, and methods for the analysis and detection of microbial adaptation strategies. Antibiotics: Methods and Protocols guides readers through chapters on production and design, mode of action, and response and susceptibility. 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 tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Antibiotics: Methods and Protocols aims to inspire scientific work in the exciting field of antibiotic research.

In one generation, the numerous factors involved in blood coagulation have become real protein entities, isolated in pure form, expressed by recombinant DNA techniques, and subjected to structure elucidation by the modem methods of physical chemistry, viz. , X-ray diffraction, and NMR, ESR and fluorescence spectroscopy. The major milestone in this field was the breakthrough achieved by W. Bode, R. Huber and their colleagues in 1989 in of human a-thrombin, inhibited with D-Phe-Pro-Arg determining the crystal structure chioromethyl ketone. The availability of this structure will greatly facilitate the interpretation of experiments designed to gain an understanding of the interatomic interactions between this enzyme and fibrinogen and its other substrates. At the same time, it provides a rational basis for the design and synthesis of inhibitors of thrombin, the subject of this symposium. The symposium was organized in four sessions: (1) Structural features of the interaction of thrombin with substrates and inhibitors, (2) Synthetic inhibitors, (3) Hirudin and its analogues, and (4) Pharmacological and clinical considerations. This book contains summaries of most of the papers presented, and takes its rigbful place among two others that provide a comprehensive picture of our current knowledge about thrombin, viz. the 1977 volume entitled "Chemistry and Biology of Thrombin", edited by R. L. Lundblad, J. W. Fenton II, and K. G. Mann, and the 1992 volume entitled "Thrombin: Structure and Function", edited by L. J. Berliner.

A collection of readily reproducible classic and emerging molecular methods for the laboratory isolation and identification of the pathogens, viruses, and parasites that cause food-borne disease. Among the pathogens covered are specific bacteria, including Salmonella spp, Campylobacter spp., Listeria spp., and Bacillus spp.; viruses, including noroviruses and enteroviruses; and parasites, including Cryptosporidium and seafood nematode worms. The protocols follow the successful Methods in Biotechnology (TM) series format, each offering step-by-step laboratory instructions, an introduction outlining the principles behind the technique, lists of the necessary equipment and reagents, and tips on troubleshooting and avoiding known pitfalls.

Cancer is a complex disease. Only 5-10% of human cancers are hereditary in nature. Many of us think of environmental agents when we think of carcinogens. The environment includes all that surrounds us, and environmental influences include not only chemical, physical and biological toxicants, but also diet and lifestyle. In this broadest sense, the environment contributes substantially in the development of human cancer. This book will describe how environment contributes to malignant transformation leading to profound changes in the genetic and signaling networks that control the functioning of the cell. It will critically discuss the understanding of the effects of environment on the development, progression and metastasis of cancer with current knowledge of the signaling networks that support functioning of transformed human cells. Genes and environmental factors that influence the origins of cancer are not necessarily the same as those that contribute to its progression and metastasis. Susceptibility gene variants for each specific cancer are being identified with emerging evidence of gene environment interaction. Gene-environment interactions will be discussed through each specific cancer-based approach to address the question of how genetic variations can influence susceptibility to the individual type of cancer. It will also highlight and summarize epigenetic changes that increase the risk for susceptibility to a particular type of cancer, particularly in the presence of specific environmental factors. Thus, this book will contain chapters from the world s experts focused on the current evidences that support the role of environment in the cancer etiology and in the growth of malignant lesions, and discuss who may be susceptible to environmental influences."

Antipsychotic (neuroleptic) drugs have become some of the biggest blockbusters of the early 21st century, increasingly prescribed not just to people with 'schizophrenia' or other severe forms of mental disturbance but for a range of more common psychological complaints. This book challenges the accepted account that portrays antipsychotics as specific treatments that target an underlying brain disease and explores early views that suggested, in contrast, that antipsychotics achieve their effects by inducing a state of neurological suppression. Professional enthusiasm for antipsychotics eclipsed this understanding, exaggerated the benefits of antipsychotics and minimized or ignored evidence of their toxic effects. The pharmaceutical industry has been involved in expanding the use of antipsychotics into territory where it is likely that their dangers far outweigh their advantages.

This comprehensive volume focuses on anti-inflammatory nutraceuticals and their role in various chronic diseases. Food and Drug Administration (FDA) approved drugs such as steroids, non-steroidal anti-inflammatory drugs (NSAIDS), statins and metformin have been shown to modulate inflammatory pathways, but their long-term intake has been associated with numerous side effects. This means that there is enormous potential for dietary agents that can modulate inflammatory pathways in humans. Leading experts describe the latest research on the role of anti-inflammatory nutraceuticals in preventing and treating chronic diseases.

Many advances have been made in the field of thermoregulation in the past few years. These include our understanding of Fever, which is now considered not simply a rise in deep body temperature foHowing infection, but just one aspect, though perhaps the most easily measured, of the Acute Phase of the Immune Response. Classification and identification of the Cytokines and the availability of recombinant material has greatly aided this research. Similarly, our understanding of the Hypothalamo-Pituitary Adrenal Axis has altered our way of thinking about temperature regulation. Of importance are the problems associated with adverse climatic conditions and survival, and the problems encountered by the neonate and the hibernator. At the biochemical level, our knowledge of the control of heat production and the role of brown adipose tissue is rapidly advancing. All these issues and many others were discussed at a Symposium 'Thermal Physiology 1993' held in Aberdeen, Scotland in August 1993 under the auspices of the Thermal Physiology Commission of the International Union of Physiological Sciences. Six main aspects of the subject of temperature regulation are included in this book, namely, Fever (including the Acute Phase of the Immune Response and Thermoregulatory Peptides), Neurophysiology of Thermoregulation, Neonatal Thermoregulation, Mechanisms of Heat Production, Ecological and Behavioural Thermoregulation, and Emerging Themes in Thermoregulation.

Medicine has entered a golden age in which therapeutic agents are becoming widely available due to advances in basic science and technology. As such, many drugs have been developed that target inflammatory processes and/or the immune system. This book is intended for health professionals examining the modulation of inflammation by immunotherapeutic drugs. The immune system fills the primordial role of host defense and resistance to infections with pathogenic microorganisms. Several hematopoietic-derived cells constituting the innate and adaptive immune systems cooperate to provide barriers for microbial colonization and/or promote pathogen destruction within the host. Conversely, many immune cells are also involved in the pathogenesis and propagation of chronic inflammatory diseases. The beginning of this book details various components of the immune system including the cell types, lymphoid tissues, soluble cytokines and surface molecules that are essential for host defense. Breakdowns in immune tolerance, or dysregulated immune responses to antigens derived from self tissues or innocuous sources, can lead to the development of autoimmunity or chronic inflammatory diseases. Pathophysiologic roles for the immune system are detailed in corresponding chapters on autoimmunity, epithelial surfaces (lungs, skin, intestine), and transplantation, with special emphasis placed on immunotherapeutic drug targets. The last section of the book focuses on treatments that stimulate our immune system to specifically target and fight infectious diseases and cancer. In each chapter, the medications used to treat various diseases/conditions in terms of their mechanism of action and other pharmacologic properties are detailed. Chapters begin with a table showing drug names and classifications. The importance of basic science and clinical trials cannot be understated in the context of drug development. As such, the discovery of certain medications that had a lasting impact in medicine and pharmacy are highlighted in chapter subsections named "Bench to Bedside." Several clinical applications of immunotherapeutic drugs are described within end-of -chapter case studies including practice questions. The Pharmacology of Immunotherapeutic Drugs is a reference for immunologists and clinicians (medical doctors, pharmacists, nurses) examining the modulation of inflammatory processes by a variety of medications targeting the cells and mediators of our immune system.