Toxicogenomics is a new multidisciplinary field concerned with elucidating how the entire genome is involved in biological responses of organisms exposed to environmental toxicants and stressors. Toxicogenomics combines information from studies of genomic-scale mRNA profiling by microarray analysis, cell-wide or tissue-wide protein profiling (proteomics), genetic susceptibility related to single nucleotide polymorphism, and computational models to understand the roles of gene-environment interactions. This book makes a valuable addition to the laboratory bookshelf of all scientists and practitioners studying toxicology, environmental science, drug development, and pharmaceutical safety. As toxicogenomics makes a revolutionary impact on environmental health, drug safety, and risk assessment in 21st-century toxicology, this volume serves as an essential sourcebook.

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.

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.

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."

This unique book is the only one to discuss various new techniques developed to enhance the application of nanoparticulate drug delivery systems using surface modification of nanoparticles. The understanding of the surface characteristics nano-particles is growing significantly with the advent of new analytical techniques. Polymer chemistry is contributing to the development of many new versatile polymers which have abilities to accommodate many different, very reactive chemical groups, and can be used as a diagnostic tool, for better targeting, for more effective therapeutic results as well as for reducing the toxic and side effects of the drugs. Surface modification of such polymeric nanoparticles has been found by many scientists to enhance the application of nanoparticles and also allows the nano particles to carry specific drug molecule and disease /tumor specific antibodies which refine and improve drug delivery. Surface Modification of Nanoparticles for Targeted Drug Delivery is a collection essential information with various applications of surface modification of nanoparticles and their disease specific applications for therapeutic purposes.

oltage-gated calcium channels are essential mediators of a range of physiological functions, including the communication between nerve Vcells, the regulation of heart beat, muscle contraction, and secretion of hormones such as insulin. Consequently, these channels are critical phar macological targets in the treatment of a variety of disorders, such as epi lepsy, hypertension, and pain. Voltage-gated calcium channels have there fore been subject to intense study by numerous investigators over the past few decades, and an immense body of work has accumulated. In this book, we provide the first comprehensive overview of our current state of knowl edge concerning this exciting field of research. Leading off with a general review of calcium signaling and techniques to measure calcium channel ac tivity, the book delves into a provocative overview of the history of the cal cium channel field, contributed by one of the key pioneers in the field. Dr. Richard Tsien. This is followed by an in depth review of the biochemical and molecular biological characterization of calcium channel genes by Drs. Catterall and Snutch whose research has resulted in major advances in the calcium channel field. A number of chapters are dedicated towards various aspects of calcium channel structure and function, including channel gat ing, permeation, modulation and interactions with members of the exo- totic machinery-contributed by both established leaders and rising stars in the field."

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.

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.

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.

This book explains the pharmacological relationships between the various systems in the human body. It offers a comprehensive overview of the pharmacology concerning the autonomic, central, and peripheral nervous systems. Presenting up-to-date information on chemical mediators and their significance, it highlights the therapeutic aspects of several diseases affecting the cardiovascular, renal, respiratory, gastrointestinal, endocrinal, and hematopoietic systems. The book also includes drug therapy for microbial and neoplastic diseases. It also comprises sections on immunopharmacology, dermatological, and ocular pharmacology providing valuable insights into these emerging and recent topics. Covering the diverse groups of drugs acting on different systems, the book reviews their actions, clinical uses, adverse effects, interactions, and subcellular mechanisms of action. It is divided into 11 parts, subdivided into several chapters that evaluate the basic pharmacological principles that govern the different types of body systems. This book is intended for academicians, researchers, and clinicians in industry and academic institutions in pharmaceutical, pharmacological sciences, pharmacy, medical sciences, physiology, neurosciences, biochemistry, molecular biology and other allied health sciences.

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.

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.

As the pharmaceutical industry continues to advance, new techniques in drug design are emerging. In order to deliver optimal care to patients, the development of innovative pharmacological techniques has become a widely studied topic. The Handbook of Research on Molecular Docking-Based Drug Design and Discovery investigates the evolution of pharmaceutical design and computational approaches in the field of molecular docking. Highlighting theoretical backgrounds and emergent research in the area of computer-assisted drug design, this publication is a pivotal source for professionals, researchers, medical chemists, pharmaceutical experts, and students interested in innovative practices and findings within the fields of computational chemistry and pharmaceutical sciences.

Project managers in drug development are the driving force behind the coordination of efforts. This book provides a practical reference for project managers in the pharmaceutical and biotech drug development industry, with the goal of assisting in creating an efficient and effective team structure and environment. The text details the role of project managers at each stage of drug development, the key interfaces that the PM will need to work closely with, and essential tools of the trade including frequently used techniques and methodologies. This book is useful for both entry-level and advanced-level PMs, as well as non-project managers from other functions. Features Includes authors' recent experience with improved tactics and technologies/software at various stages of drug development. Provides the most up-to-date and best practices, techniques, and methodologies in project management. Details the role of the PM at each stage of drug development, including working with the key interfaces throughout the process. Diverse audience including nonproject managers in clinical development, clinical operations, regulatory affairs, medical affairs, clinical pharmacology, and biostatistics. Provides templates and timelines for critical paths from development to commercialization and has potential as a textbook on relevant courses.

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

Glyco-engineering is being developed as a method to control the composition of carbohydrates and to enhance the pharmacological properties of monoclonal antibodies (mAbs) and other proteins. In Glycosylation Engineering of Biopharmaceuticals: Methods and Protocols, experts in the field provide readers with production and characterization protocols of glycoproteins and glyco-engineered biopharmaceuticals with a focus on mAbs. The volume is divided in four complementary parts dealing with glyco-engineering of therapeutic proteins, glycoanalytics, glycoprotein complexes characterization, and PK/PD assays for therapeutic antibodies. Written in the highly successful Methods in Molecular Biology (TM) series format, 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 cutting-edge, Glycosylation Engineering of Biopharmaceuticals: Methods and Protocols serves as an ideal guide for scientists striving to push forward the exciting field of engineered biopharmaceuticals.

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

Nanoengineering, energized by the desire to find specific targeting agents, is leading to dramatic acceleration in novel drug design. However, in this flurry of activity, some issues may be overlooked. This is especially true in the area of determining dosage and evaluating the effects of multiple agents designed to target more than one site of metastasis. Offering the unique perspective of a medical physicist who has worked directly with cancer patients for over three decades, Radiopharmaceuticals: Introduction to Drug Evaluation and Dose Estimation starts by exploring the recent history and current state of the field. Then, citing key research and practical examples, the author looks at how to run studies and employ estimation and evaluation methods that lead to the best multiple agents with the least amount of trial and error. He discusses methods that will allow researchers to more rigorously: Differentiate one radiopharmaceutical (RP) from another Estimate radiation doses Correlate results across various species to realize more informed data from clinical trials Incorporating developments in nanotechnology and radiology, with the ultimate goal of achieving personalized patient-specific treatment, this book crosses disciplines to addresses a range of topics including: Preclinical RP development Organization of clinical trials Determination of activity in vivo Modeling and temporal integration with a look at the mass law for tumor uptake as a function of tumor size (discovered by the author) Absorbed dose estimates with and without clinical correlations Multiple-modality therapy Dr. Lawrence Williams has devoted most of his life's research to tumor detection and treatment, and his discoveries continue to influence evolving therapies. As s a medical physicist, he is eminently qualified to bring unique insight into the discussion of radiopharmaceutical dosage rates and efficacy.

This book highlights the behavioral and neurobiological issues relevant for drug development, reviews evidence for an innovative approach for drug discovery and presents perspectives on multiple special topics ranging from therapeutic drug use in children, emerging technologies and non-pharmacological approaches to cognitive enhancement.

By the year 2050, the world's population is expected to reach nine billion. To feed and sustain this projected population, world food production must increase by at least 50 percent on much of the same land that we farm today. To meet this staggering challenge, scientists must develop the technology required to achieve an "evergreen" revolution -- one that increases crop productivity without degrading natural resources. With 30 percent new material, the updated and revised third edition of Growth and Mineral Nutrition of Field Crops covers all aspects of crop growth and mineral nutrition that contribute to sustainable, high-yield agriculture. Bringing together international scientific knowledge of crop production and the impacts of agriculture on the environment, this book: * Includes two new chapters on remediation of heavy-metal contaminated soils and cover crops * Covers theoretical and practical aspects of mineral nutrition of field crops * Provides recommendations for judicious use of fertilizers, which will reduce cost of crop production and enhance high crop yields without risking environmental pollution * Provides growth patterns for annual crops and forages * Includes a handful of color pictures of nutrient deficiencies for easy diagnostic purposes To make the book as practical as possible, each chapter is supported by experimental results and extensive references. A large number of figures and tables are also included to save readers time when researching. The overall emphasis of this reference is on the soil's ability to sustain high crop yields and a healthy human population.

An authority on anti-drug policy and crack since it became a popular street drug in the mid-1980s, Belenko traces the development of America's policy response in the context of changes in policy that were underway when crack first appeared. He summarizes the state of our knowledge about crack, its pharmacological properties, its use and effects on health and behavior, and its distribution. Moreover, he makes recommendations about policies to deal with the next drug epidemic. This empirical analysis and public policy study is intended for teachers, graduate students, researchers, practitioners, and policymakers in drug control and treatment, criminal justice law enforcement, and in public administration.

This detailed volume examines computer-aided drug discovery (CADD), a crucial component of modern drug discovery programs that is widely utilized to identity and optimize bioactive compounds for the development of new drugs. With a focus on the methods that are commonly used in the early stage of drug discovery, chapters explore computer simulation, structure prediction, conformational sampling, binding site mapping, docking and scoring, in silico screening, and fragment-based drug design. In addition to the state-of-the-art theoretical concept, this book also includes step-by-step, readily reproducible computational protocols as well as examples of various CADD strategies. The limitations and potential pitfalls of different computational methods are discussed by experts, and tips and advice for their applications are suggested. Practical and thorough, Computer-Aided Drug Discovery serves as an ideal addition to the Methods in Pharmacology and Toxicology series, guiding researchers toward their lab's goals with this exciting and versatile technology.