This detailed book arrives as there is an increasing need for multiplex biomarker readouts for improved clinical management and to support the development of new drugs by pharmaceutical companies, due to continuous technical developments and new insights into the high complexity of many diseases. Chapters explore the basic technology platforms being applied in the fields of genomics, proteomics, transcriptomics, metabolomics, and imaging, which are currently the methods of choice in multiplex biomarker research. The book also describes the chief medical areas in which the greatest progress has been made and highlight areas where further resources are required. Written for the highly successful Methods in Molecular Biology series, methodology 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. Multiplex Biomarker Techniques: Methods and Applications serves as an ideal resource for a wide variety of researchers interested in these vital multiplex techniques.

This innovative volume introduces Trajectory Analysis, a new systems-based approach to measuring nonlinear dynamics in continuous change, to public health and epidemiology. It synthesizes influential strands of statistical and probability science (including chaos theory and catastrophe theory) to complement existing methods and models used in the health fields. The computational framework featured here pinpoints complex cause-and-effect processes in behavioral change as individuals and populations adjust to health interventions, with examples from neuroscience and cardiology. But this is no mere academic exercise, as the author illustrates how these methods can be harnessed toward finding real-world answers to longstanding public health problems, starting with treatment recidivism. Included in the coverage: * The universality of physical principles in the analysis of health and disease * The problem of recidivism in healthcare intervention studies * Stability and reversibility/irreversibility of health conditions * Chaos theory and sensitive dependence on initial conditions * Applications in health monitoring and geographic systems * Simulations, applications, and the challenge for public health A stimulating new take on statistics with powerful implications for future study, practice, and policy, Trajectory Analysis in Health Care should interest public health epidemiologists, researchers, clinicians, and policymakers.

Classic biostatistics, a branch of statistical science, has as its main focus the applications of statistics in public health, the life sciences, and the pharmaceutical industry. Modern biostatistics, beyond just a simple application of statistics, is a confluence of statistics and knowledge of multiple intertwined fields. The application demands, the advancements in computer technology, and the rapid growth of life science data (e.g., genomics data) have promoted the formation of modern biostatistics. There are at least three characteristics of modern biostatistics: (1) in-depth engagement in the application fields that require penetration of knowledge across several fields, (2) high-level complexity of data because they are longitudinal, incomplete, or latent because they are heterogeneous due to a mixture of data or experiment types, because of high-dimensionality, which may make meaningful reduction impossible, or because of extremely small or large size; and (3) dynamics, the speed of development in methodology and analyses, has to match the fast growth of data with a constantly changing face. This book is written for researchers, biostatisticians/statisticians, and scientists who are interested in quantitative analyses. The goal is to introduce modern methods in biostatistics and help researchers and students quickly grasp key concepts and methods. Many methods can solve the same problem and many problems can be solved by the same method, which becomes apparent when those topics are discussed in this single volume.

Valproic acid was first synthesized in 1882 by Burton, but there was no known clinical use until its anticonvulsant activity was fortuitously discovered by H. Meunier in 1963 in the laboratory of G. Carraz. The first clinical trials of the sodium salt of valproate were reported in 1964 by Carraz. It was marketed in France in 1967 and was released in the United States in 1978 for the treatment of epilepsy. Since then, valproate has established itself worldwide as a major antiepileptic drug against several types of seizures. Clinical experience with valproate has continued to grow in recent years, including use of valproate for diseases other than epilepsy, for example in bipolar disorders and migraine. In this book, emphasis is placed on the scientific background leading to the discovery of valproate and its clinical development into one of the most widely and successfully used antiepileptic drugs, a real milestone in drug therapy. The current state of knowledge of valproate is reviewed by experts in the field, including new hypotheses on its mechanisms of action, its metabolism into pharmacologically active metabolites, its unique distribution characteristics, its undesirable hepatotoxic and teratogenic adverse effects, and its various clinical uses. The monograph is aimed at a broad readership, particularly neurologists, psychiatrists and basic scientists working in the field of epilepsy research. Furthermore, the book also deals with structure-activity relationships of valproate as well as of its metabolites and analogs and should therefore attract researchers working in medicinal chemistry.

This book begins the discourse on post-trial access to drugs in developing countries. Underlying ethical issues in global health inequalities and global health research serve as the context of the debate. Due to rampant allegations of violations of rights of research participants, especially in developing countries, it discusses the regulatory infrastructure and ethical oversight of international clinical research, thus emphasizing the priority of safeguarding the rights of research participants and host populations as desiderata in conducting clinical trials in developing countries. This is the first book that analyzes the major obstacles of affordable access to drugs in developing countries - patent and non-patent factors and how they can be overcome through a middle ground approach and a new paradigm to establish global health justice which includes national and global health responsibilities. The book also deals extensively with all complex aspects of the discourse on affordable access to drugs in developing countries, including intellectual property law, international regulations, political and cultural systems, international trade agreements. Furthermore it contains a robust ethical debate and in-depth analysis. The book crafts a paradigm of global health justice involving a sliding scale of national and global responsibilities for the realization of the right to health in general and access to drugs in particular.

What drives a scientist to edit a book on a speci c scienti c subject such as chiral mechanisms in separation methods? Until December 2005, the journal Analytical Chemistry of the American Chemical Society (Washington, DC) had an A-page section that was dedicated to simple and clear presentations of the most recent te- niques or the state of the art in a particular eld or topic. The "A-page" section was prepared for a broad audience of chemists including industrial professionals, s- dents as well as academics looking for information outside their eld of expertise. 1 Daniel W. Armstrong, one of the editors of this journal and a twenty-year+ long friend, invited me to present my view on chiral recognition mechanisms in a simple and clear way in an "A-page" article. In 2006, the "A-page" section was maintained as the rst articles at the beginning of each rst bi-monthly issue but the pagination was no longer page distinguished from the regular research articles published by the journal. During the time between the invitation and the submission, the A-page section was integrated into the rest of the journal and the article appeared as (2006) Anal Chem (78):2093-2099.

A major challenge confronting the pharmaceutical scientist working with protein formulation is the instability during processing, storage and use of the protein drug. This book reviews stability aspects encountered since the pioneering isolation of insulin in 1921. An introductory chapter, treating insulin purity and stability in historical perspective, is followed by a chapter with a description of the structure of insulin. The main part of the book is a comprehensive review of the literature dealing with stability of insulin in pharmaceutical formulation, including biological stability and the physical and chemical decomposition of insulin. The physical stability (i.e. the tendency of insulin to form insoluble fibrils) is reviewed as are methods to stabilize insulin for long-term use in infusion pumps. The book will be of interest to research and clinical pharmacologists involved with insulin and other protein-based drug substances.

Sildenafil, for the treatment of erectile dysfunction, is one of the first products that has made its way successfully from basic NO (nitrous oxide) research, to clinical routine therapy. Sidenafil, part of the Milestones in Drug Therapy series, presents the major breakthroughs in the field of NO physiology and pharmacology that led to the development of the drug, as well as clinical applications in one source guide.

Written by leading experts in the field, each chapter covers aspects of clinical use and experience, pharmacokinetics, pharmacodynamics, biochemistry, and cultural science.

The idea for this book came from discussions among participants in a symposium on biotechnical applications at the "Pacifichem 89" meeting in Honolulu. It was the majority opinion of this group that a volume dedicated to biotechnical and biomedical applications of PEG chemistry would enhance research and development in this area. Though the book was conceived at the Honolulu meeting, it is not a proceedings of this symposium. Several groups who did not participate in this meeting are repre sented in the book, and the book incorporates much work done after the meeting. The book does not include contributions in all related areas to which PEG chemistry has been applied. Several invited researchers declined to parti.: ipate, and there is not enough space in this single volume to properly cover all submissions. Chapter I-an overview of the topic-discusses in brief applications not given detailed coverage in specifically devoted chapters. The following topics are covered: introduction to and fundamental properties of PEG and derivatives in Chapters 1-3; separations using aqueous polymer two-phase partitioning in Chapters 4-6; PEG-proteins as catalysts in biotechnical applications in Chapters 7 and 8; biomedical applications of PEG-proteins in Chapters 9-13; PEG modified surfaces for a variety of biomedical and biotechnical applications in Chapters 14-20; and synthesis of new PEG derivatives in Chapters 21 and 22."

Drug-related problems in the elderly is intended to serve as a source of information and clinical support in geriatric pharmacotherapy for students as well as all health care professionals, e.g. physicians, nurses and pharmacists. Pharmacotherapy is of great importance to all mankind. Drugs are however powerful and must be handled appropriately. This is especially important for elderly patients. Drug-related problem is not a major subject in most university programmes in medicine or pharmacy. When there is no speci c course, there is often no book covering the topic. In our view, as teachers at various university courses, there has been a shortage of literature that re ects the most important aspects of drug-related problems in the elderly. Medical practitioners, nurses and pharmacists, need to have this knowledge to be able to serve their patients in the best way. This book covers most aspects of drug-related problems in the elderly. With b- ter knowledge of drug-related dif culties and risks we hope that elderly will have fewer drug-related problems and bene t more from their pharmacotherapy.

Endocannabinoids have tremendous therapeutic potential. This book introduces readers to our current understanding of the neurobiology of endocannabinoids and related systems, detailing their pathophysiological role and therapeutic potential. Authors, experienced clinical investigators, present and analyze results of recent clinical trials as well as the development of new therapeutic strategies and medicines.

Since the subject of high dilution effects is still a subject for debate, this volume provides evidence in support of effects from control clinical studies, clinical records from veteran physicians, controlled experiments on animals and plants, and in vitro tests without any organisms (Chapter II). An overview of the methods for preparing drugs at ultra high dilution is also provided as well as the basic principles of homeopathy, which has been alleviating human suffering through the use of these drugs for several hundred years (Chapter I). Chapter III provides physical basis of high dilutions as evidence from the NMR, IR, UV and fluorescence spectra of those drugs. Since water is used as the diluents media, the structure and dynamics of water polymers in relation to high dilution are discussed in order to facilitate easy comprehension of this physical aspect, the basic principles of spectroscopy are also described. Chapter IV focuses on the mechanism of action of potentized drugs in the living system, discussing the structure of the cell, the plasma membrane, the integral proteins on the membrane, the interaction between these proteins and high dilutions and the manifestations of the therapeutic effects of high dilutions. Some aspects, peculiar to homeopathy, such as the chief miasm psora, and the literalities and time modalities of symptoms and drug action are interpreted from a scientific perspective. Chapter IV ends with a brief discussion on water structures and the origin of life to show the natural evolution of high dilution effects. The book not only helps in understanding the physical basis of high dilutions and their mechanism of action in organisms but provides many new avenues of investigation into this interdisciplinary field of science.

This volume - like the NATO Advanced Research Workshop on which it is based - addresses the fundamental science that contributes to our understanding of the potential risks from ecological terrorism, i.e. dirty bombs, atomic explosions, intentional release of radionuclides into water or air. Both effects on human health (DNA and systemic effects) and on ecosystems are detailed, with particular focus on environmentally relevant low-dose ranges. The state-of-the-art contributions to the book are authored by leading experts; they tackle the relevant questions from the perspectives of radiation genetics, radiobiology, radioecology, radiation epidemiology and risk assessment.

Protein kinase C (PKC), a family of serine-threonine kinases, rocketed to the forefront of the cancer research field in the early 1980's with its identification as an effector of phorbol esters, natural products with tumor promoting activity. Phorbol esters had long been of interest to the cancer research field due to early studies in the mouse skin carcinogenesis model, which showed that prolonged topical application of phorbol esters promoted the formation of skin tumors on mice previously treated with mutagenic agents. Research in the last years has established key roles for PKC isozymes in the control of cell proliferation, migration, adhesion, and malignant transformation. In addition, there is a large body of evidence linking PKC to invasion and cancer cell metastasis. Moreover, it is now well established that the expression of PKC isozymes is altered in various types of cancers. More importantly, small molecule inhibitors have been developed with significant anti-cancer activity. The relevance of PKC isozymes in cancer signaling is therefore remarkable. This book will have 4 sections. There will be 23 chapters. Each section will have a brief introduction by an expert in the field (~ 1-2 pages).

This book, with its 16 chapters, documents the present state of knowledge of the adenosine A receptor. It covers a wide range of information, including data from 3 studies of theoretical, molecular and cellular pharmacology, signal transduction, integrative physiology, new drug discoveries and clinical applications. It fills an important gap in the literature since no alternative source of such information is currently available. Although the A receptor is increasingly being recognized for 3 its increasing number of biological roles throughout the body and many A receptor 3 ligands have proven useful in elucidating peripheral and central pathologies, many issues remain unresolved. Moreover, research activity in this field continues to grow exponentially, resulting in a constant flow of new information. The chapters in this book cover both basic science and the relevant applications and provide an authoritative account of the current status of the field. They have enabled my goal as editor to make "A Adenosine Receptors from Cell Biology to Pharmacology and 3 Therapeutics" an up to date, scientifically excellent, reference source, attractive to basic and clinical scientists alike, a reality. Detailed understanding of the physico-chemical aspects and molecular biology of the A receptor provides a solid basis for its future development as a target for 3 adenosine-based pharmacotherapies (Chapters 2 and 3).

This book is based on the proceedings of the symposium entitled "Di rected Drug Delivery: A Multidisciplinary Problem," which was held in Lawrence, Kansas on October 17-19, 1984. The purpose of the sym posium and this book is to focus on the multidisciplinary nature of drug delivery. Development of a successful drug delivery system re quires contributions from various scientific disciplines, including pharmaceutical chemistry, analytical chemistry, medicinal chemistry, biochemistry, pharmacology, toxicology, and clinical medicine. The contents of this volume illustrate the importance of the various disci plines in identifying the problems and approaches for the develop ment of a rational and effective drug delivery system. Thus the infor mation provided herein will be of value not only to the pharmaceutical chemists who are responsible for dosage form design, but also to the pharmacokineticists, pharmacologists, and clinicians involved in bio logical evaluation of drug delivery systems. The volume should also be of interest to the analytical chemists who must provide technology to quantitcltively evaluate drug delivery. Additionally, this work will also interest the biochemists and medicinal chemists involved in drug dis covery, since the drug delivery system often plays a major role in determining the success or failure of a new drug entity. Each speaker at the symposium was requested to contribute a chapter reviewing the contribution of their major discipline to the de velopment of a successful drug delivery system."

In this book, leading-edge investigators offer effective strategies to improve current antidepressive therapies and suggest molecular, biological, and genetic approaches that will lead to the development of novel antidepressants. The contributors' critical reviews and commentaries illuminate our understanding of the mechanism(s) responsible for antidepressant action. The book's goal is to move beyond current biogenic amine-based concepts and therapies to the development of new and improved antidepressants that are more effective and have a more rapid onset than current.

This detailed volume assembles comprehensive protocols to assist with the study of structural, molecular, cell biological, and in vivo facets of GPCRs, and to enable the development of experimental tools for screening novel GPCR drugs. Sections explore the tweaking of ligands, bioluminescence and FRET approaches, specific GPCR signaling properties, as well as visualization of subcellular compartmentalization. Written for the highly successful Methods in Molecular Biology series, 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 practical, G Protein-Coupled Receptor Signaling: Methods and Protocols serves as an ideal reference for life scientists working in a variety of research fields including molecular pharmacology, cell and developmental biology, brain behavior and physiology, drug development and screening. Chapter 4 is available open access under a CC BY 4.0 license via link.springer.com.

The volumes of this classic series, now referred to simply as "Zechmeister" after its founder, L. Zechmeister, have appeared under the Springer Imprint ever since the series inauguration in 1938. The volumes contain contributions on various topics related to the origin, distribution, chemistry, synthesis, biochemistry, function or use of various classes of naturally occurring substances ranging from small molecules to biopolymers. Each contribution is written by a recognized authority in his field and provides a comprehensive and up-to-date review of the topic in question. Addressed to biologists, technologists, and chemists alike, the series can be used by the expert as a source of information and literature citations and by the non-expert as a means of orientation in a rapidly developing discipline.

The fact that tobacco ingestion can affect how people feel and think has been known for millennia, placing the plant among those used spiritually, honori?cally, and habitually (Corti 1931; Wilbert 1987). However, the conclusion that nicotine - counted for many of these psychopharmacological effects did not emerge until the nineteenth century (Langley 1905). This was elegantly described by Lewin in 1931 as follows: "The decisive factor in the effects of tobacco, desired or undesired, is nicotine. . . "(Lewin 1998). The use of nicotine as a pharmacological probe to und- stand physiological functioning at the dawn of the twentieth century was a landmark in the birth of modern neuropharmacology (Limbird 2004; Halliwell 2007), and led the pioneering researcher John Langley to conclude that there must exist some "- ceptive substance" to explain the diverse actions of various substances, including nicotine, when applied to muscle tissue (Langley 1905). Research on tobacco and nicotine progressed throughout the twentieth century, but much of this was from a general pharmacological and toxicological rather than a psychopharmacological perspective (Larson et al. 1961). There was some attention to the effects related to addiction, such as euphoria (Johnston 1941), tolerance (Lewin 1931), and withdrawal (Finnegan et al. 1945), but outside of research supported by the tobacco industry, addiction and psychopharmacology were not major foci for research (Slade et al. 1995; Hurt and Robertson 1998; Henning?eld et al. 2006; Henning?eld and Hartel 1999; Larson et al. 1961).

Over the past twelve years, the Centre for Medicines Research has held a series of Workshops on a number of topics related to the drug discovery and development process. The major objective of these Workshops has been to provide an international forum for regula tory, academic and industry representatives to debate together, and suggest solutions to, specific problems. The meeting reported in this volume represents a departure from this approach, in that the par ticipants were drawn largely from the pharmaceutical industry. Senior clinicians, pharmacologists and toxicologists from companies in Europe, the USA and Japan met in May 1994 to discuss a scientific rationale for the conduct of toxicity studies to support the clinical development of new medicines, and to begin to work towards an industry consensus. Achievement of such a consensus is seen as an important step in the process leading towards international harmon isation of the recommendations on the timing of toxicity studies in relation to clinical trials."

Paul H. Axelsen concisely summarizes all the essential medical data concerning the leading antimicrobials used in fighting infectious diseases and clearly illustrates their mechanisms of action. The agents described range from antibacterial and antifungal to antiparasitic and antiviral agents, and include immunomodulators and immunizing agents. For each drug discussed, the book allows rapid access to the essential facts concerning its structure and mechanism of action, the spectrum of its activity, its pharmacokinetics, its adverse effects, and its resistance. This book provides medical students, physicians, and allied health professionals with rapid access to the core principles of antimicrobial pharmacology, and a foundation for decisions about the use of antimicrobials in daily practice.