Hypericum extract preparations are used extensively in many countries to treat mildly to moderately depressed patients. While this was based previously on traditional experience, extensive research over the last 10 years has given a broad preclinical and clinical basis to justify the use of Hypericum as an antidepressant. This book reviews the available data related to the biochemical, functional, and behavioural pharmacology of Hypericum and its active constituents. The clinical chapters overview the evidenced basis for its use as an antidepressant, initial data in anxiety and somatoform disorders, and the site effect profile of Hypericum and its possible relevant drug interactions. The known pharmacokinetics of the relevant constituents and the biopharmaceutical quality of commercially available Hypericum preparations are also discussed.

This compelling volume provides a broad and accessible overview on the rapidly developing field of social neuroscience. A major goal of the volume is to integrate research findings on the neural basis of social behavior across different levels of analysis from rodent studies on molecular neurobiology to behavioral neuroscience to fMRI imaging data on human social behavior.

Efforts to describe and model the molecular structure of biological membranes go back to the beginning of the last century. In 1917, Langmuir described membranes as a layer of lipids one molecule thick [1]. Eight years later, Gorter and Grendel concluded from their studies that "the phospholipid molecules that formed the cell membrane were arranged in two layers to form a lipid bilayer" [2]. Danielli and Robertson proposed, in 1935, a model in which the bilayer of lipids is sequestered between two monolayers of unfolded proteins [3], and the currently still accepted fuid mosaic model was proposed by Singer and Nicolson in 1972 [4]. Among those landmarks of biomembrane history, a serendipitous observation made by Alex Bangham during the early 1960s deserves undoubtedly a special place. His fnding that exposure of dry phospholipids to an excess of water gives rise to lamellar structures [5] has opened versatile experimental access to studying the biophysics and biochemistry of biological phospholipid membranes. Although during the following 4 decades biological membrane models have grown in complexity and functionality [6], liposomes are, besides supported bilayers, membrane nanodiscs, and hybrid membranes, still an indisputably important tool for membrane b- physicists and biochemists. In vol. II of this book, the reader will fnd detailed methods for the use of liposomes in studying a variety of biochemical and biophysical membrane phenomena concomitant with chapters describing a great palette of state-of-the-art analytical technologies.

Specialist Periodical Reports provide systematic and detailed review coverage of progress in the major areas of chemical research. Written by experts in their specialist fields the series creates a unique service for the active research chemist, supplying regular critical in-depth accounts of progress in particular areas of chemistry. For over 80 years the Royal Society of Chemistry and its predecessor, the Chemical Society, have been publishing reports charting developments in chemistry, which originally took the form of Annual Reports. However, by 1967 the whole spectrum of chemistry could no longer be contained within one volume and the series Specialist Periodical Reports was born. The Annual Reports themselves still existed but were divided into two, and subsequently three, volumes covering Inorganic, Organic and Physical Chemistry. For more general coverage of the highlights in chemistry they remain a 'must'. Since that time the SPR series has altered according to the fluctuating degree of activity in various fields of chemistry. Some titles have remained unchanged, while others have altered their emphasis along with their titles; some have been combined under a new name whereas others have had to be discontinued. The current list of Specialist Periodical Reports can be seen on the inside flap of this volume.

The specific topic, "Isoquinolines And Beta-Carbolines As Neurotoxins And Neuroprotectants - New Perspectives In Parkinson`S Disease Therapy," was chosen in light of accumulating neurobiological evidence indicating that, in addition to exogenous neurotoxins (e.g., 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine [MPTP]), endogenous compounds may play an important role in the most common neurodegenerative disorders (e.g., Parkinson`s disease). Two groups of amine related compounds, which appeared chemically like MPTP, were detected in human brain and cerebrospinal fluid (CSF): ss-carbolines (BCs) and tetrahydroisoquinolines (TIQs). These are heterocyclic compounds formed endogenously from phenylalanine/tyrosine (TIQs) and tryptophan, tryptamine, and 5-hydroxytryptamine (BCs), respectively and exert a wide spectrum of psychopharmacological and behavioral effects. The TIQs and BCs may bind to their own high affinity sites on neuronal membranes associated with or located close to the receptors of neurotransmitters. Research on TIQs and BCs is stimulated also by their possible role in pathological conditions, especially parkinsonism and alcoholism. Recently, clinical interest has been spurred by their role as neuroprotective, and even neurorestorative, anticonvulsant and antiaddictive, substances. In this book we are going to summarize, for the first time, the results from behavioral, neurochemical and molecular experiments, which demonstrate a wide spectrum of TIQs and BCs effects - from their rather mild neurotoxic actions to the important neuroprotective and antiaddictive properties. Additionally, the recent results of experimental studies in vivo have allowed a much better understanding and simultaneous comparison of the neurochemical and molecular mechanisms underlying the neuroprotective and neurotoxic actions of endogenous TIQs and BCs and have pointed to the possibility of their therapeutic applications in neurodegenerative diseases such as Parkinson's disease.

Founded in 1959 by its current Editor, the series has moved from its initial focus on medicinal chemistry to a much wider scope. Today it encompasses all fields concerned with the development of new therapeutic drugs and the elucidation of their mechanisms of action, reflecting the increasingly complex nature of modern drug research. Invited authors present their biological, chemical, biochemical, physiological, immunological, pharmaceutical, toxicological, pharmacological and clinical expertise in carefully written reviews and provide the newcomer and the specialist alike with an up-to-date comprehensive list of prime references. Each volume of Progress in Drug Research contains fully cross-referencing indices which link the books together, forming a virtually encyclopaedic work. The series thus serves as an important, time-saving source of information for researchers concerned with drug research and all those who need to keep abreast of the many recent developments in the quest for new and better medicines.

In transfusion medicine the scientific fundamentals of immunology have had a considerable clinical impact. Transfusion may suppress the immunity but some patients could suffer disadvantages including GvHD, alloimmunisation and possible cancer, where white cells (WBC) play pivotal roles in this phenomenon, presenting antigens and producing cytokines. A clinical application of this practice is LAK-cells targeted against cancer. MHC on the WBC may provide additional immunological modulations through series of secondary messengers. Thus reduction of WBC in the blood and bone marrow may be advantageous for patients. On the other hand, sharing a part of MHC or making the transplanted white cells anergic by storage may be even more advantageous for patients. CMV infection could mimic part of this MHC. UV radiation is effective in the inactivation of the WBC although filters are easy means for such removal. However, their accurate quantification requires flow cytometry that has considerable potential application in blood transfusions. Idiotypic antibody could play an important role in platelet theory. However, the potential infection risks in transfusion like HIV and HCV remain, but application of molecular biological methods like PCR or RT/PCR has great potentials in detection of infectious diseases, transplantation and genetic disorders. Immuno affinity purified concentrates, like factor IX and protein C, could reduce patients' immune functions, where in the future protein C could be derived from transgenic animals. Advances are sure to emerge through adoptive immunotherapy and gene therapies are exciting prospects when genes transferred into lymphocytes could be used to correct cell mediated immune deficiency, as in ADA.

The contents of this book will be organized into three sections. The first section defines the scope, impact and behaviour of cancer regimen-related toxicities and frames the issue of balancing treatment success and physiological cost. In the second segment of the book, the most current thinking around the pathobiology of specific, common, and representative toxicities is presented by leading researchers and translational scientists. The final portion of the book discusses the common biological relationships between toxicities, bioinformatical approaches to analysing key and common pathways, and strategies for the development of effective interventions.

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.

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.

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.

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).