Focused on the discovery of precise molecular targets for the development of the cancer preventive agents, "Cancer Prevention: Dietary Factors and Pharmacology" provides researchers and non-researchers with practical methodologies for developing and validating small molecule and phytochemical-derived drug discovery and mechanisms by which these compounds can modulate distinct target proteins involved in oncogenic signaling. While this volume is primarily focused toward cancer prevention research, the range of techniques demonstrated in the book also provides an introduction of cancer prevention research methods to researchers outside the field. Chapters deal with a critical discussion of both laboratory and clinical topics, with each chapter containing both a discursive section along with a detailed methods section. As part of the "Methods in Pharmacology and Toxicology" series, this meticulous volume includes the kind of key implementation advice that seeks to ensure successful results in the lab.

Practical and authoritative, "Cancer Prevention: Dietary Factors and Pharmacology" aims to guide research toward identifying molecular targets and conducting human studies with phytochemicals which would, ideally, provide an enhanced approach to the goal of personalized cancer prevention.

Radiophannaceutical research has recently undergone a major change in direction. In past years it has been concerned mainly with the development of perfusion tracers, the biodistribution of which reflect the regional blood flow to areas of major organs such as the heart and brain. However, a major new direction of interest now lies in the development of receptor-binding radio-tracers which can be used to perform in-vivo characterisation of diseased tissues and it is likely that much of the future research in this field will follow this direction. The difficulties in developing such tracers are considerable. The researcher must first identify a promising target for radiopharmaceutical development. High specific activity radioactive molecules must be designed and synthesised which will both bind to the target receptor with high affinity, and also have the physicochemical characteristics which will allow them to reach the target site in sufficient quantity while at the same time showing minimal uptake in non-target tissues. Thus the knowledge base required for radiophannaceutical development has now expanded beyond the limits of radiopharmaceutical chemistry to include aspects of biochemistry, molecular biology and conventional drug design. The portfolio of basic knowledge required to support current radiopharmaceutical development is changing and scientists working in this arena need to be trained in this regard. At the same time, the very latest developments in the field need to be communicated to the scientific community in order to stimulate the advancement of this exciting new direction of research.

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.

This book is intended to serve as a resource for analysts in developing and troubleshooting sample preparation methods. These are critical activities in providing accurate and reliable data throughout the lifecycle of a drug product. This book is divided into four parts: * Part One covers dosage form and diluent properties that impact sample preparation of pharmaceutical dosage forms and the importance of sampling considerations in generating data representative of the drug product batch. * Part Two reviews specific sample preparation techniques typically used with pharmaceutical dosage forms. * Part Three discusses sample preparation method development for different types of dosage forms including addressing drug excipient interactions and post extraction considerations, as well as method validation and applying Quality by Design (QbD) principles to sample preparation methods. * Part Four examines additional topics in sample preparation including automation, investigating aberrant potency results, green chemistry considerations for sample preparation and the ideal case where no sample preparation is required for sample analysis.

In this era of biotechnology there have been many books covering the fundamentals of recombinant DNA technology and protein chemistry. However, not many sources are available for the pharmaceutical develop ment scientist and other personnel responsible for the commercialization of the finished dosage forms of these new biopharmaceuticals and other products from biotechnology. This text will help to fill this gap. Once active biopharmaceutical molecules are candidates for clinical trial investigation and subsequent commercialization, a number of other activities must take place while research and development on these molecules continues. The active ingredient itself must be formulated into a finished dosage form that can be conveniently used by health care professionals and patients. Properties of the biopharmaceutical molecule must be clearly understood so that the appropriate finished product formulation can be developed. Finished product formulation development includes not only the chemical formulation, but also the packaging system, the manufacturing process, and appropriate control strategies to assure such good manufacturing practice attributes as safety, identity, strength, purity, and quality."

Expert researchers and physician/clinicians describe in detail the newest and most commonly used technologies today in this rapidly advancing field. The authors provide readily reproducible methods for assessing the functional consequences of a certain polymorphism, evaluate the variety of genotyping platforms currently available, and discuss the management of pharmacogenomic information. Highlights include techniques for making a snapshot of the allele-specific variation in human gene expression, genome wide analysis of allele-specific expression using oligo microarrays, in vivo assays with HaploChIP, SNP genotyping in DNA pools, and PharmGKB, the pharmacogenetics and pharmacogenomics knowledge base. The methodologies for genotyping include denaturing high-performance liquid chromarography, pyrosequencing, kinetic-fluorescence detection, mass spectrometry, and TaqMan assay for insertion/deletions.

This book is written for researchers, undergraduate students and postgraduate students, physicians and traditional medicine practitioners who develop research in the field of neurosciences, phytochemistry and ethnopharmacology or can be useful for their practice. Topics discussed include the description of depression, its biochemical causes, the targets of antidepressant drugs, animal and cell models commonly used in the research of this pathology, medicinal plants and bioactive compounds with antidepressant activity used in traditional medicine, advances in nanotechnology for drug delivery to the brain and finally the future challenges for researchers studying this pathology.

This volume serves as a valuable handbook for the development of nanomedicines made of polymer nanoparticles because it provides researchers, students, and entrepreneurs with all the material necessary to begin their own projects in this field. Readers will find protocols to prepare polymer nanoparticles using different methods, since these are based on the variety of experiences that experts encounter in the field. In addition, complex topics such as, the optimal characterization of polymer nanoparticles is discussed, as well as practical guidelines on how to formulate polymer nanoparticles into nanomedicines, and how to modify the properties of nanoparticles to give them the different functionalities required to become an efficient nanomedicine for different clinical applications. The book also discusses the translation of technology from research to practice, considering aspects related to industrialization of preparation and aspects of regulatory and clinical development.

This book provides an overview of critical components of cell signaling machinery and its role in epithelial morphogenesis, proliferation, invasions and angiogenesis in human cancer and discusses novel types of protein kinase pathways.

This book continues as volume 6 of a multi-compendium on Edible Medicinal and Non-Medicinal Plants. It covers edible fruits/seeds used fresh, cooked or processed into other by-products, or as vegetables, cereals, spices, stimulant, edible oils and beverages. It covers selected species from the following families: Sapindaceae, Sapotaceae, Schisandraceae, Solanaceae, Thymelaeaceae, Urticaceae, Vitaceae and Winteraceae. This work will be of significant interest to scientists, researchers, medical practitioners, pharmacologists, ethnobotanists, horticulturists, food nutritionists, agriculturists, botanists, conservationists, lecturers, students and the general public. Topics covered include: taxonomy; common/English and vernacular names; origin and distribution; agroecology; edible plant parts and uses; botany; nutritive and pharmacological properties, medicinal uses and research findings; nonedible uses; and selected references.

A powerful collection of readily reproducible cutting-edge techniques for characterizing the ligand or substrate binding of neurotransmitter receptors and transporters. The procedures cover interdisciplinary interactions for monoamine transporters, amino acid transporters, ionotropic receptors, metabotropic glutamate receptors, GABA receptors, and other G protein-coupled receptors. By illuminating how neurons in the central nervous communicate with other, these techniques can lead to the development of novel therapeutic strategies for neurological diseases.

Nearly thirty years ago, in 1974, the volume on Angiotensin edited by Irvine H.Page and F. Merlin Bumpus expanded the Handbook of Experimental Pharmacology. Even after two decades the multiplicity of its actions appears not to have been fully discovered. To call attention to its many functions is one of the purposes of this book. This new edition of the volume on Angiotensin attempts to provide an updated account of the knowledge and findings accumulated since the complexity of angiotensin was so accurately recognized.

This book presents a series of perspectives on the therapeutic potential of the ritual and clinical use of the Amazonian hallucinogenic brew ayahuasca in the treatment and management of various diseases and ailments, especially its role in psychological well-being and substance dependence. Biomedical and anthropological data on the use of ayahuasca for treating depression, PTSD, and substance dependence in different settings, such as indigenous contexts, neo-shamanic rituals, contemporary therapeutic circles, and in ayahuasca religions, in both South and North America, are presented and critiqued. Though multiple anecdotal reports on the therapeutic use of ayahuasca exist, there has been no systematic and dense reflection on the topic thus far. The book brings the therapeutic use of ayahuasca to a new level of public examination and academic debate. The texts in this volume stimulate discussion on methodological, ethical, and political aspects of research and will enhance the development of this emergent field of studies.

U-50,488 and the K receptor. Part II: 1991-1998.- Quantitative structure-activity relationships of antihypertensive agents.- Combinatorial chemistry: Polymer supported synthesis of peptide and nonpeptide libraries.- From genome to drug - optimising the drug discovery process.- Phosphodiesterase 4 (PDE4) inhibitors in asthma and chronic obstructive pulmonary disease (COPD.- Index Vol. 53.- Index of titles, Vol. 1-53.- Author and paper index, Vol. 1-53.

Artemisinin, a sesquiterpene lactone originally extracted from the medicinal plant Artemisia annua L., is an effective antimalarial agent, particularly for multi-drug resistant and cerebral malaria. However, the concentration of artemisinin in the plant is very low. Because the chemical synthesis of artemisinin is complicated and not economically feasible in view of the poor yield of the drug, the intact plant remains the only viable source of artemisinin production. Therefore, it is necessary to increase the concentration of artemisinin in A. annua to reduce the cost of artemisinin based antimalarial drugs. Plant scientists have focused their efforts on A. annua for a higher artemisinin crop yield. With the present volume, we are bringing together the research which is being done on this plant throughout the world and future possibilities for scientists and researchers who want to work on it.

This text offers state of the art contributions written by world renown experts which provide an extensive background on specific classes of antibiotics and summarize our understanding as to how these antibiotics might be optimally used in a clinical situation. The book explores pharmacodynamics methods for anti-infective agents, pharmacodynamics of antibacterial agents and non-antibacterial agents, as well as pharmacodynamic considerations and special populations. As part of the Methods in Pharmacology and Toxicology series, chapters include detailed insight and practical information for the lab. Comprehensive and cutting-edge, Antibiotic Pharmacodynamics serves as an ideal reference for scientists investigating advances in antibiotic pharmacodynamics now finding their way into the antibiotic development process used for licensing new antibiotics.

Within the past few years, it has become recognized that the immune system communicates to the brain. Substances released from activated immune cells (cytokines) stimulate peripheral nerves, thereby signaling the brain and spinal cord that infection/inflammation has occurred. Additionally, peripheral infection/inflammation leads to de novo synthesis and release of cytokines within the brain and spinal cord. Thus, cytokines effect neural activation both peripherally and centrally. Through this communication pathway, cytokines such as interleukin-1, interleukin-6 and tumor necrosis factor markedly alter brain function, physiology and behavior. One important but underrecognized aspect of this communication is the dramatic impact that immune activation has on pain modulation. The purpose of this book is to examine, for the first time, immune-to-brain communication from the viewpoint of its effect on pain processing. It is aimed both at the basic scientist and health care providers, in order to clarify the major role that substances released by immune cells play in pain modulation. This book contains chapters contributed by all of the major laboratories focused on understanding how cytokines modulate pain. These chapters provide a unique vantage point from which to examine this question, as the summarized work ranges from evolutionary approaches across diverse species, to the basics of the immune response, to the effect of cytokines on peripheral and central nervous system sites, to therapeutic potential in humans.

The introduction of chlorpromazine in 1953, and haloperidol in 1958, into clinical practice dramatically altered the therapy of schizophrenic patients. Although representing by no means a cure for this severe psychiatric ill ness, it allowed, for the first time, to adequately control the severe hallu cinations and delusional beliefs which prevent these patients from leading a more or less independent life. Indeed these antipsychotics (and the many congeners that were to follow) significantly reduced the number ofchronic schizophrenic inpatients in psychiatric clinics all over the world. However soon after their introduction it became clear that, like all other available drugs, antipsychotics were by no means miracle drugs. In fact, two major problems appeared. First, the antipsychotics had very little effect on the so-called negative or defect symptoms, like social isolation, apathy and anhedonia, and secondly virtually all antipsychotics produced a number of side-effects, of which the neurological (often called extra pyramidal) side-effects were the most troublesome. Especially the tardive dyskinesia, which occurred in about 15 to 20% of the patients after pro longed treatment, represented a major problem in the treatment of schizo phrenic patients."

Edward J. Massaro and a panel of leading biomedical researchers and clinical practitioners review, in-depth, the status of our current knowledge concerning the biochemistry of copper in general and its role in health and disease in particular. Drawing on the wealth of new information emerging from the molecular biology revolution, these experts survey the most important research areas of copper pharmacology and toxicology, including copper proteins and transport, copper toxicity and therapeutics, and copper metabolism and homeostasis. They also discuss the molecular pathogenesis of copper in a variety of metabolic diseases, Menkes and Wilson's diseases and occipital horn syndrome, as well as the role of copper in Parkinson's disease, prion disease, familial amytrophic lateral sclerosis (ALS), and Alzheimer's disease.

In the United States, 20.8 million children and adults, 7% of the population, have diabetes. While an estimated 14.6 million have been diagnosed, 6.2 million have yet to be diagnosed. Worldwide diabetes afflicts 150 million people. The World Health Organization estimates that by 2025 that figure will double. Diabetes is responsible for more deaths than AIDS and breast cancer, combined. It is a leading cause of blindness, kidney failure, amputations, heart complications and stroke. Treatment of Type 1 and Type diabetes has changed radically over the past few years. There are new opportunities for treating the key abnormality in diabetes, increased blood glucose, by effective agents such as new insulin preparations and oral agents. Increasing so-called non-glycemic intervention is of prime importance. Blood pressure lowering therapies, anti-cholesterol strategies, and specific treatment related to complications is becoming increasingly important. Pharmacotherapy of Diabetes is a unique, invaluable guide to all aspects of the pharmacological treatment of diabetes, covering basic concepts and an in-depth review of current and future therapies. This work provides an overview for the new changes in therapies that can be implemented in clinical practice and treatment of the diabetic patient.

The NATO Advanced Study Institute of "Molecular and Applied Aspects of Oxida- tive Drug Metabolizing Enzymes" was held in Tekirova, Antalya, Turkey, from August 31 to September 11, 1997. This Institute was the third of a series of the NATO ASIs on a similar topic relating to the enzymes of oxidative metabolism of xenobiotics. The first NATO ASI in this series, entitled "Molecular Aspects of Monooxygenases and Bioactiva- tion of Toxic Compounds" (NATO ASI Series A: Life Sciences, Vol. 202), was held in

Nitric Oxide (NO) is a pleitropic, ubiquitous modulator of cellular functions. Aryl nitrite and glyceryl trinitrate, representative intravasadilators, were introduced as therapeutic agents more than a century ago for relief from acute attacks of angina. The vasodilator action is mediated by the release of NO following treatment. NO has important therapeutic applications in several diseases such as inflammatory diseases, erectile dysfunction, inflammation, pain and neural protective activity. However, the role of NO in cancer and its application in therapy has received little attention. This monograph will be the first to focus on studies that investigate the role of NO in tumor cell pathogenesis, growth, angiogenesis, response to cytotoxic therapies and NO translational applications in cancer therapy, alone or in conjunction with other therapies.

F. Schweda and A. Kurtz: Regulation of Renin Release by Local and Systemic Factors M. Krauss and V. Haucke: Shaping Membranes for Endocytosis B.M. Jockusch and P.L. Graumann: The Long Journey: Actin on the Road to Pro- and Eukaryotic Cells B. Colsoul, R. Vennekens and B. Nilius: Transient Receptor Potential (TRP) Cation Channels in Pancreatic ss cells