The metabolic syndrome is a common syndrome affecting about 20 % of the adult population in Europe, and probably the prevalence is of the same magnitude in other industrialised countries worldwide. It is mainly caused by western lifestyle resulting in abdominal obesity, but also a genetic predisposition plays a role. This syndrome, which is linked to leisure lifestyle and overeating/obesity, can develop into type 2 diabetes, cardiovascular disease and cancer. Therefore, proper treatment and prevention are heavily needed. This book discusses lifestyle intervention and treatment, specifically with pharmacological compounds, in order to formulate a strategy for treating the metabolic syndrome in the daily clinic.

The principal objective of this symposium was to bring together investigators from all over the world who work in diverse areas of research but share a common interest in the physiologic and pathophysiologic funetions of the nueleoside adenosine. In 1978, the "International Conference on Physiological and Regulatory Funetions of Adenosine and Adenine Nueleotides," held in Banff, Canada, served as an effective catalyst in enabling scientists with differ ent points of view to exchange information and ideas on this subject. Since 1978, the amount of research on different as peets of adenosine metabolism, mechanism of action, transport, and function in various tissues (in both nor maI and abnormal states) has increased exponentially, and there was an urgent need for another meeting for updating information on this burgeoning subject. The focus of the meeting was extremely sharp, but the scope of the subject material was very broad. Scientists categorized as chemists, biochemists, physiologists, pharmacologists, and immunologists, working with cells and eelI fragments, with tissues such as heart, brain, musele, fat, kidney, and with human beings having immune deficiency diseases participated in the sym posium. They had an opportunity to air their differences, reinforce their areas of agreement, and, most important, they educated each other with respeet to research on adenosine; it is hoped that they also enriched their own research programs from the information they gained from their fellow participants."

Each year pharmaceutical companies invest billions of dollars in clinical trials of drugs used for the treatment of central nervous system diseases. Due to enormous progress in basic pharmaceutical research in recent years, controlled tests of new medications are flourishing and these trials have rapidly become an intense focus of practical medical research.

Aware of the complexities presented in the design, execution, and evaluation of clinical trials, Marc Hertzman and Douglas E. Feltner bring together a collection of essays that dissect the scientific, psychosocial, political, and ethical concerns that must be examined for any CNS trial. The internationally known contributors examine concerns about ethics and cost; the FDA and its regulatory impact; and the implementation of a variety of trials, for disorders such as schizophrenia, alcoholism, eating disorders, insomnia, and aggression. The editors carefully consider important social issues including the considerations related to women's special needs; and the relative merits of psychotherapy and medications.

The Handbook of Psychopharmocology Trials provides an up-to- date and stimulating exploration of important issues on the subject of CNS Clinical trials.

Understanding the role of hedgehog signaling in cancer is critically important for novel cancer therapeutics. The hedgehog pathway is a major pathway regulating cell differentiation, tissue polarity, stem cell maintenance and cell proliferation. It is known by now that activation of this pathway occurs in a variety of human cancer, including basal cell carcinomas (BCCs), medulloblastomas, leukemia, gastrointestinal, lung, ovarian, breast and prostate cancers. This book provides insightful views suitable for graduate students, medical students, undergraduate students, basic and clinical scientists, cancer patients as well as the general public.

This book is composed of four major sections: The perception of risk, where authorities from the field of environmental psychology and risk analysis describe the backgrounds and mechanisms of cognitive behavior and the effects of emotional and publicity factors on perception and acceptance of risk. The management of infection-defined risk, the core of public and political anxiety. Here the book illustrates how safe the current blood supply has become over the past decade in at least the majority of industrialized countries in the world. The management of immune-defined risks has been the Cinderella of blood transfusion and transfusion medicine up till now. Risk management in clinical practice: optimal versus maximal is the section where the real virtue of reality comes to life through valuable contributors by authors from the field of clinical blood banking, heavily involved consumers organizations (WFH), the Cochrane Institute of Medical Sciences and National Health Services Center for reviews and dissemination, and international policy makers and regulative bodies like the Council of Europe and the European Commission. When the reader is first confronted with a poem illustrating the reality of virtue, written by one of the editors noted for his talent in anecdotal medical poetry, the scene is set for the virtue of reality in the management of risk in blood transfusion.

This volume provides an up-to-date account of the achievements pertaining to the application of capsaicin and capsaicin-like molecules in the therapy of various human ailments such as pain, non-allergic rhinitis, obesity, tumors and gastrointestinal, dermatologic and urologic disorders. It discusses the basic functionsof the capsaicin receptor (TRPV1), its mechanisms of action and its role in physiological and pathological processes. The text focuses on the most recent progress in the use of capsaicin and capsaicin-like molecules as a therapeutic agent and highlights potential pharmaceutical implications of further TRPV1 research. The chapters are written by noted experts in their fields of endeavor. This book offers both clinicians and researchers valuable resource and reference material on the subject that will stimulate future research. "

Comprehensive and state of the art, the second edition of Pharmacotherapy of Depression offers major revisions of every chapter and the addition of new chapters by expert contributors. The first chapter reviews the neurobiology of depression, which lays the groundwork for understanding the mechanisms of action of antidepressants. In the next chapter, a review of the general principles guiding the diagnosis and medication treatment of unipolar depression is provided. The clinical pharmacology of antidepressants is reviewed in some detail, supplemented by tables that provide information on dosing, indications, and metabolism. Augmentation strategies are reviewed, including the use of non-traditional agents. The chapters that follow next address the use of antidepressants in special populations, such as the elderly and depressed individuals with psychosis, bipolar disorder, substance abuse, and post traumatic stress disorder. The complex issues involving the diagnosis and treatment of depression during pregnancy is thoroughly reviewed in Chapter 8 and provides a synthesis of the scientific literature in the area, one that is noted for contradictory and controversial findings, as well as guidelines for prescribing. The next chapter then provides an overview of the treatment of depression in the pediatric population, highlighting clinical concerns such as suicide risk. The book concludes with two chapters at the interface of medicine and psychiatry in the treatment of mood disorders: managing depression in primary care settings and depression associated with medical illnesses. The outstanding clinician-scientists who have contributed to this volume are all leaders in their fields and represent a broad spectrum of renowned institutions. A timely contribution to the literature, The Pharmacotherapy of Depression, Second Edition, offers busy clinicians from many disciplines a strong scientific foundation that seamlessly transitions into practical recommendations for clinical practice. The result is another gold-standard guide to the safe and effective use of the latest antidepressant medications.

This volume comprises papers presented at the 40th Erice Course "From Molecules to Medicine: Structure of Biological Macromolecules and Its Relevance in Combating New Diseases and Bioterrorism," May 29 to June 8, 2008. The papers span the breadth of material presented, which emp- size the practical aspects of modern macromolecular crystallography and its applications to medicine. Topics addressed span from the selection of targets, through to structure determination, interpretation and exploitation. A particular theme that emerges is the dependence of modern structural science on multiple experimental and computational techniques. It is both the development of these techniques and their integration that will take us forward in the future. The NATO ASI directors worked alongside, and offer deep gratitude to Prof. Sir Tom Blundell, Director of the International School of Crystal- graphy, Dr Colin Groom, Dr Neera Borkakoti, Dr John Irwin and Prof. Lodovico Riva di Sanseverino, who were in turn supported by a number of local facilitators. The course was financed by NATO as an Advanced Study Institute. Additional support was given by the European Crystallographic Association, the International Union of Biochemistry and Molecular Biology, the Int- national Union of Crystallography, the University of Bologna, AstraZeneca, Roche, Merck & Co., Boehringer Ingelheim, Bruker Corporation, Douglas Instruments, Informa UK, the Department of Pharmaceutical Chemistry, TTP Lab Tech, University of California at San Francisco. Joel L. Sussman and Paola Spadon

Introducing Palliative Care is the ideal introductory text for training students in medicine and qualified healthcare professionals in the area of palliative care. The sixth edition has been fully revised in line with current practice and the latest edition of the Palliative Care Formulary (PCF7).

Over the past 50 years, more than 100,000 scientific papers, not to mention popular articles and books, have been written about Selenium. These publications continue to appear without showing any sign of diminution today. This mass of writing makes it very difficult for anyone, who is not a dedicated and specialized scientist, to get a clear picture of what is now known about the element and its role in human health. The second edition of Selenium in Food and Health takes into account the considerable amount of fresh information that has been published over the past decade, by investigators from a wide range of specialties, not all of which, at first glance, might appear to have much to do with human health. It presents information in an easy-to-follow manner for the general reader who wants to make an informed judgment about the competing claims for and against Selenium's value as a nutritional supplement,

The first book was on "Theory and Practice" of antibiotic stewardship in its broadest sense -the how to do it and the do's and don'ts. The second, on "Controlling resistance" was very much on the relationships between use and resistance and beginning to home in on the hospital as the main generator of resistance, but mainly looking at it from a disease/clinical perspective. The last 3 chapters on MRSA, ended where the 3rd book will take off. "Controlling HAI " will concentrate on specific MDR organisms highlighting their roles in the current pandemic of HAI and emphasizing that the big issue is not so much infection control but antibiotic control, in the same way that antibiotic over-reliance/ over-use has caused the problem in the first place. Up 'till now the emphasis for controlling MRSA, C diff and all the other MDROs has very much been on IC, which clearly isn't working. This book will gather all the evidence for the increasingly popular view that much more must be done in the area of antibiotic policies/ stewardship, especially when we are in danger of a "post antibiotic" era, due to a real shortage of new agents in the pipeline.

This comprehensive review provides a systematic, unbiased analysis, critique and summary of the available literature and generates novel clinical decision-making algorithms which can aid clinicians and scientists in practice management and research development. Potential mechanisms for the identified drug interactions are deduced from available preclinical and in vitro data which are interpreted in the context of the in vivo findings. Current limitations and gaps in the literature are summarized, and potential future research directions / experimentations are also suggested. In addition to the main objective to review the available clinical pharmacokinetic and pharmacodynamic drug interactions associated with WHO-recommended antimalarial drugs on the market today (i.e. chloroquine, amodiaquine, sulfadoxine, pyrimethamine, mefloquine, artemisinin, artemether, artesunate, dihydroartemisinin, artemotil, lumefantrine, primaquine, atovaquone, proguanil, piperaquine and quinine), this book also provides succinct chapter summaries on the epidemiology of malaria infection, diagnosis and therapeutics, in vivo pharmacology and chemistry, preclinical pharmacology, in vitro pharmacodynamics, in vitro reaction phenotyping, and in vitro drug-drug interaction data associated with the identified antimalarial drugs.

Anesthesia and Analgesia in Laboratory Animals focuses on the special anesthetic, analgesic, and postoperative care requirements associated with experimental interventions. Fully revised and updated this new edition provides the reader with agents, methods, and techniques for anesthesia and analgesia that ensure humane, reproducible, and successful procedural outcomes. The content is structured in six sections. The first deals with ethical, regulatory, and scientific considerations. Chapters in this section include US and international regulatory considerations, and optimization of anesthesia and analgesia. Part two is dedicated to the principles of anesthesia and analgesia with chapters covering topics in a non-species-specific way, but with a slant towards laboratory animals, including relevant pharmacology of the agents. Part three covers Anesthetic equipment and monitoring. Section four deals with periprocedural care including dedicated chapters to the assessment and management of pain in laboratory species. Part five provides practical considerations by species, including relevant anatomy, physiology, and behavior of a broad range of lab animal species. Part six closes the book with special topics covering management of chronic pain, fetus and neonate interventions, considerations for in-vivo imaging and the study of pain. Anesthesia and Analgesia in Laboratory Animals is the complete reference for veterinarians involved in lab animal research as well as senior graduate, graduate students, post-docs, and researchers who utilize animals in biomedical research.

The field of the excitatory amino acids was born when L-glutamate and L-aspartate were found to be potent convulsants (Hayashi, 1954), and were subsequently found to excite neurons directly (Curtis, Phillis, and Watkins, 1959). Although these studies initiated the hypothesis of glutamate-mediated neurotransmission, it was noted that the ubiquitous actions of glutamate could also reflect a general, nonspecific property of glutamate on neuronal mem branes. It was not until 20 years later that pharmacological, physiological, and biochemical studies provided convincing evidence for a neurotransmitter role for glutamate in the mammalian central nervous system (CNS). With the critical demonstration that the pharmacologically defined glutamate receptors mediate synaptic currents, glutamate rapidly became widely accepted as a majorneurotransmitter by the mid-1980s. This breakthrough, together with the simultaneous findings that glutamate receptors are involved in many essential, as well as pathological, processes in the CNS, instantly transformed the study of glutamate receptors into one of the fastest-growing and most exciting areas of neuroscience. With the cloning of numerous ionotropic glutamate receptor subunits over the last six years, the field has experienced another dramatic acceleration in the understanding of receptor action and in providing the first clear insights into the molecular bases underlying the wealth of pharmacological and physiological data on these receptors."

If the antibody industry is to achieve its full potential in the next decade, the individual technical potentials must be exploited, the limitations must be addressed, and lessons learned must be applied both to current purification methods and to the new technologies that continue to emerge. This book presents an overview of the current advances applied in the manufacture of monoclonal antibody including:
-concepts in development of manufacturing strategies,
-importance of antibody fragments,
-application of chromatography method development,
-quality control,
-effect of expression on antibody properties,
-virus removal and safety,
-pharmacokinetics,
-regulatory aspects.

Antibodies Volume 1: Production and Purification together with Volume 2: Novel Technologies and Therapeutic Use will be of great value to all of those who are actively working in the field of antibodies.
Volume 2: Novel Technologies and Therapeutic Use brings to the forefront current advances in novel technologies for the manufacturing of monoclonal antibodies and also their extensive clinical importance. Following on from Antibodies Volume 1: Production and Purification, this volume concentrates on:
-new technologies in the manufacture of monoclonal antibodies,
-the application of antibodies in cancer therapy and functional genomic therapy,
-the importance of antibodies and prospects of antibody engineering for the future.

This book presents an essential overview of beta-lactams and their medicinal value and use in the preparation of other biologically active compounds. Written by internationally respected authors, the individual chapters explore beta-lactams' synthesis, their mechanism of formation, biological effects, and function as base materials for other heterocycles of major importance.

A Pharmacology Primer: Techniques for More Effective and Strategic Drug Discovery, Sixth Edition features the latest research surrounding the application of pharmacology in drug discovery in an effort to equip readers with a deeper understanding of complex and rapid changes in this field. Written by well-respected pharmacologist, Terry P. Kenakin, this primer is an indispensable resource for anyone involved in drug discovery. This edition has been reorganized for better flow and clarity and includes material on new technologies for screening (virtual, DNA encoded libraires, fragment-based) and a major section on phenotypic (target agnostic) screening for new leads and determination of drug targets. With full color illustrations as well as new examples throughout, this book remains a top reference for all industry and academic scientists and students directly involved in drug discovery or pharmacologic research. New material includes a discussion of the determination of target engagement, including numerous new ways to demonstrate the physical interaction of molecules with drug targets and new drug candidates such a mRNA, gene therapy, antibodies and information on CRISPR and genomics.

Physiological, pharmacological and molecular biological data generated over the past three decades have demonstrated the existence of two major families of extracellular receptors, the P1, a family of four G-protein coupled receptors and the P2, a family of at least 12 receptors responsive to purine (ATP, ADP) and pyrimidine (UTP) nucleotides through which adenosine and ATP can function as extracellular messengers. The present two-part volume represents an integrated compendium of invited chapters by leading researchers in the area focusing on advances in the understanding of purinergic and pyrimidinergic signaling systems, their role(s) in tissue function and pathophysiology and advances in developing potential new medications based on the modulation of P1 and P2 receptor signaling processes. The volumes will thus provide the reader with a topical, comprehensive and integrated overview of this important area.

Transfusion medicine is an excellent way for the healthy community to help the sick. However, service providers and patients have much to gain from the establishment of guidelines concerning when and how it is used. An important first step would be to introduce informed consent for transfusion recipients. Discussions with blood banks and assessment of clinical demand would also be necessary, taking into account the needs of patients and physicians, and the availability of products. Unfortunately, the efficacy and safety of transfusion products can be difficult to ascertain. Furthermore, although major advances have been made in safety, the risks of giving and receiving blood are still seen as high. It is vital to learn what underlies that perception and how to counter it. The policies and protocols used to establish surgical criteria for blood transfusions should be explored. Finally, clinical audits can help evaluate the risk: benefit ratio of transfusion; they may be carried out by hospital transfusion committees but are likely to be more successful with the support of national and international legislative and regulatory bodies. The implementation of appropriate initiatives now will improve the outlook for the future of transfusion medicine, perhaps with ex-vivo expanded haemopoietic cell therapy as the next milestone. All these key points and controversies are explored in this book, which paints a broad picture of the current status and future trends in transfusion medicine.

Drug Metabolism: Current Concepts provides a comprehensive understanding of the processes that take place following ingestion of a medicinal agent or xenobiotic, with an emphasis on the crucial role of metabolism (biotransformation). How a sound knowledge of these phenomena is incorporated into the design of effective new drug candidates is also explained. The user-friendly text focuses on concepts rather than extraneous details and is supported by many illustrated examples of biotransformations as well as frequent references to current critical reviews and articles highlighting the nature of research objectives in this vibrant area of medicinal development. The final topic on strategies for drug design relies on the background provided by the rest of the book. This book is ideally suited as an advanced text for courses in drug metabolism for students of medicine, pharmacy, pharmacology, biochemistry; and for courses in drug design and drug delivery for students of medicinal chemistry. It is also appropriate for professional seminars or courses that relate to the fate of a drug in the body, drug interactions, adverse reactions and drug design.

GABA is the principal inhibitory neurotransmitter in the CNS and acts via GABAA and GABAB receptors. Recently, a novel form of GABAA receptor-mediated inhibition, termed "tonic" inhibition, has been described. Whereas synaptic GABAA receptors underlie classical "phasic" GABAA receptor-mediated inhibition (inhibitory postsynaptic currents), tonic GABAA receptor-mediated inhibition results from the activation of extrasynaptic receptors by low concentrations of ambient GABA. Extrasynaptic GABAA receptors are composed of receptor subunits that convey biophysical properties ideally suited to the generation of persistent inhibition and are pharmacologically and functionally distinct from their synaptic counterparts. This book highlights ongoing work examining the properties of recombinant and native extrasynaptic GABAA receptors and their preferential targeting by endogenous and clinically relevant agents. In addition, it emphasizes the important role of extrasynaptic GABAA receptors in GABAergic inhibition throughout the CNS and identifies them as a major player in both physiological and pathophysiological processes.