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.

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.

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.

This book reviews recent breakthroughs in anti-cancer drug discovery. Building on the previous volume in the series, it outlines some of the most significant developments that have occurred in the field in the subsequent period that have led to new drug approvals or promising clinical candidates. The volume is divided into chapters that each relate to a specific protein or protein class. Each chapter provides an overview of the underlying biology and then emphasises the medicinal chemistry strategies and tactics that led to the most significant drugs and drug candidates. A summary of clinical data and the future outlook for the field is also provided. Each chapter is authored by experts in the topic and who have themselves made significant contributions to their respective fields.

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.

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 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.

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.

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.

"Molecular Pharmacognosy" discusses the application of molecular biology in resource science and authentication of traditional Chinese medicine (TCM). This book reviews the latest developments in pharmacognosy, introduces a series of new views and insights, presents the hotspots and focus of the field of study on molecular pharmacognosy, and predicts a new direction of study on the resource science of TCM. Furthermore, the book also provides an open communications platform for the development of molecular pharmacognosy. This book is intended for biomedical scientists and researchers in the fields of molecular biology, traditional medicine and natural pharmaceutics.

Professor Lu-qi Huang is Director of the Collaborating Centre of the World Health Organization for Traditional Medicine (Chinese Materia Medica) and Vice-Chairman of the Australia Chinese Association for Biomedical Sciences Inc.

This volume sets out to consider a range of cardiac diseases for which drugs may play a therapeutic role by virtue of their effects on aspects of the immune system. The book reviews diseases of the heart which may involve an immunopharmacological component, and methods and techniques for the study of physiological and biochemical functions in the heart. An important focus is the immunopharmacology of the coronary vascular endothelium and the role of cellular and biochemical components of the immune system in the pathogenesis of atherosclerosis. The content also includes a review of the use of immunologically relevant agents in the setting of cardiac transplantation from aclinical perspective. Immunotherapy has a definite role to play in cardiology to a greater or lesser extent than other forms of intervention, depending on the type of cardiac disease. Immunopharmacology of the Heart aims to identify and clarify this role and points to potential developments of the future. Immunopharmacology of the Heart is a volume for the SYSTEMS theme of The Handbook of Pharmacology. In common with all other volumes it contains standardized illustrations and terms/abbreviations (glossaries of illustrations and terms published at the back of the volume). Other topics covered include: Leukocytes and their role in ischaemic heart disease. Complement activation. Sudden cardiac death. The stunned myocardium and reperfusion injury.

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.

This volume covers the current status of research in the neurobiology of motivated behaviors in humans and other animals in healthy condition. This includes consideration of the psychological processes that drive motivated behavior and the anatomical, electrophysiological and neurochemical mechanisms which drive these processes and regulate behavioural output. The volume also includes chapters on pathological disturbances in motivation including apathy, or motivational deficit as well as addictions, the pathological misdirection of motivated behavior. As with the chapters on healthy motivational processes, the chapters on disease provide a comprehensive up to date review of the neurobiological abnormalities that underlie motivation, as determined by studies of patient populations as well as animal models of disease. The book closes with a section on recent developments in treatments for motivational disorders.

This essential work, edited by two researchers at London 's famous Queen Mary 's medical school targets one of the most important areas in medical development today. These days, antibody therapeutics are the treatment of choice for several autoimmune and oncological conditions. They are, indeed, becoming the molecules of choice for further combination therapies and cell engineering. In this timely work, a slew of expert in the field of drug development summarize all the current developments and clinical successes.

This book provides a comprehensive overview of metabonomics and gut microbiota research from molecular analysis to population-based global health considerations. The topics include the discussion of the applications in relation to metabonomics and gut microbiota in nutritional research, in health and disease and a review of future therapeutical, nutraceutical and clinical applications. It also examines the translatability of systems biology approaches into applied clinical research and to patient health and nutrition. The rise in multifactorial disorders, the lack of understanding of the molecular processes at play and the needs for disease prediction in asymptomatic conditions are some of the many questions that system biology approaches are well suited to address. Achieving this goal lies in our ability to model and understand the complex web of interactions between genetics, metabolism, environmental factors and gut microbiota. Being the most densely populated microbial ecosystem on earth, gut microbiota co-evolved as a key component of human biology, essentially extending the physiological definition of humans. Major advances in microbiome research have shown that the contribution of the intestinal microbiota to the overall health status of the host has been so far underestimated. Human host gut microbial interaction is one of the most significant human health considerations of the present day with relevance for both prevention of disease via microbiota-oriented environmental protection as well as strategies for new therapeutic approaches using microbiota as targets and/or biomarkers. In many aspects, humans are not a complete and fully healthy organism without their appropriate microbiological components. Increasingly, scientific evidence identifies gut microbiota as a key biological interface between human genetics and environmental conditions encompassing nutrition. Microbiota dysbiosis or variation in metabolic activity has been associated with metabolic deregulation (e.g. obesity, inflammatory bowel disease), disease risk factor (e.g. coronary heart disease) and even the aetiology of various pathologies (e.g. autism, cancer), although causal role into impaired metabolism still needs to be established. Metabonomics and Gut Microbiota in Nutrition and Disease serves as a handbook for postgraduate students, researchers in life sciences or health sciences, scientists in academic and industrial environments working in application areas as diverse as health, disease, nutrition, microbial research and human clinical medicine.

Investigating Biological Systems Using Modeling describes how to apply software to analyze and interpret data from biological systems. It is written for students and investigators in lay person's terms, and will be a useful reference book and textbook on mathematical modeling in the design and interpretation of kinetic studies of biological systems. It describes the mathematical techniques of modeling and kinetic theory, and focuses on practical examples of analyzing data. The book also uses examples from the fields of physiology, biochemistry, nutrition, agriculture, pharmacology, and medicine.
Key Features:
* Contains practical descriptions of how to analyze kinetic data
* Provides examples of how to develop and use models
* Describes several software packages including SAAM/CONSAM
* Includes software with working models

27 chapters cover the distribution, economic importance, conventional propagation, micropropagation, tissue culture studies, and in vitro production of important medicinal and other pharmaceutical compounds in various species of Anchusa, Brucea, Catharanthus, Chrysanthemum, Coleus, Corydalis, Coreopsis, Emilia, Ginkgo, Gloriosa, Hypericum, Inonotus, Leucosceptrum, Lilium, Linum, Mosses, Nandina, Penstemon, Prunus, Pteridium, Quassia, Ribes, Senecio, Taraxacum, Thermopsis, Vanilla, and Vitiveria. Like the previous five volumes on medicinal and aromatic plants (Volumes 4, 7, 15, 21, and 24), this book contains a wealth of useful information for advanced students and researchers in the field of plant biotechnology and chemical engineering, pharmacy, botany and tissue culture.

Thoroughly revised and updated, "Optimization in Drug Discovery: In Vitro Methods, Second Edition" presents a wide spectrum of in vitro assays including formulation, plasma binding, absorption and permeability, cytochrome P450 (CYP) and UDP-glucuronosyltransferases (UGT) metabolism, CYP inhibition and induction, drug transporters, drug-drug interactions via assessment of reactive metabolites, genotoxicity, and chemical and photo-mutagenicity assays. Written for the "Methods in Pharmacology and Toxicology" series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and tips on troubleshooting and avoiding known pitfalls. Expert authors have developed and utilized these in vitro assays to achieve drug-like characteristics in addition to efficacy properties and good safety profiles of drug candidates.

Comprehensive and up-to-date, "Optimization in Drug Discovery: In Vitro Methods, Second Edition" aims to guide researchers down the difficult path to successful drug discovery and development."

This book focuses on how obesity and sedentary lifestyles adversely affect cancer risk and survival for individuals as well as mechanisms that may underlie those associations. However, evidence is accumulating rapidly on the cost of obesity and sedentary lifestyles to society. For example, obesity is estimated to lead to costs of $147 billion in the US.6 While research on individual level interventions for weight loss and increasing physical activity have identified efficacious approaches, these changes in behavior are not maintained by many in the current environments in the US and worldwide that promote weight gain and inactivity. Research on environmental and policy approaches for addressing these problems at the societal level is needed7, 8 and is a major component of the President's Report on Childhood Obesity released in April 2010. The epidemic of overweight and obesity and the increasing sedentary lifestyles will impact the magnitude and quality of the cancer problem globally. Increasing the knowledge of scientists, clinicians, and policy experts will aid in defining new prevention and treatment methods, to reduce the impact of energy balance on cancer, with the goal to eventually reduce the burden of cancer. Hopefully, this knowledge can be translated into incentives for the general public, persons at high risk, and cancer patients and survivors to increase physical activity, reduce excess weight, and maintain energy balance lifelong.

This completely revised and enlarged 3rd edition continues the idea of the previous version to provide an up-to-date overview of blood and marrow transplantations. Indication to transplantation and pre-transplant considerations are discussed in detail before the transplant procedure with all acute and delayed procedure is described. An outlook on the latest developments and their future aspects is included, and problems and pre- and post-transplant complications are discussed. This book helps practising hematologists, oncologists,and other physicians as well as physicians in training and students to develop an idea as to when blood and marrow transplantation should be considered, what the costs are and how a donor can be selected.

This title is a comprehensive text that addresses key aspects of nanomedicine such as properties occurring at the nanoscale that have unique medical effects, great molecular knowledge of the human body and disease processes, and apparent clinical translation as opposed to narrow insufficient texts that address only a few topics and attempt to "rebrand" established drug delivery. It will clearly define the field which is needed due to the immaturity and broad nature of the field. The book is aligned with both the USA and European roadmaps for nanomedicine and will address initiatives taken in Asia that ensures timely and relevant content. In-depth chapters ensure each section is adequately covered. The nanopharmaceutical section focuses on novel drug delivery systems relevant to nanomedicine and the book has an extensive section on immune recognition at the nanoscale which has implications for in vivo applications of nanomedicines.

There is currently limited acceptance of foreign clinical data by regulatory authorities, although the reasons for repeating studies are poorly defined. There are some proven genetic differences in drug metabolism and elimination which occur with varying frequencies in different populations. In addition, there are differences in culture, environment and medical practice which can impact on drug reponsiveness. This book, a further edition in the CMR Workshop Series, reviews the proceedings of a workshop held in London in July 1993 to address these issues. The contributors review the current situation, address the scientific basis for repeating clinical trials in different ethnic groups, consider specific examples, and assess the relevance of inter-ethnic and environmental differences in responsiveness for drug development.