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

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.

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.

Biopharmaceutical medicines, the newest class of therapeutics, are quite heterogeneous and include a range of molecules such as proteins, peptides, vaccines and nucleic acids, with use in virtually all therapeutic fields (e.g. cancer and infectious diseases, vaccination, metabolic dysfunctions) and diagnostics. This edited book gives a concise and up-to-date overview of the biological features justifying the use of different human mucosa as delivery routes for biopharmaceuticals, the technological strategies that have been followed so far regarding the optimization of mucosal potentialities as well as the challenges that arise with the advent of new biopharmaceutical drugs and alternative means of administration. Following a brief introduction, the first section addresses general aspects of the biology of mucosal tissues and their unique aspects toward beneficial or deleterious interaction with biopharmaceuticals and their delivery systems. The second part reviews the different delivery strategies that have recently been investigated for different mucosal sites. The third section describes the development and clinical applications of drug delivery systems and products enclosing biopharmaceuticals for mucosal delivery, with a focus on the most successful case studies of recent years. The last section briefly centers on relevant aspects of the regulatory, toxicological and market issues of mucosal delivery of biopharmaceuticals. Scientists and researchers in the fields of drug delivery, material science, biomedical science and bioengineering as well as professionals, regulators and policy makers in the pharmaceutical, biotechnology and healthcare industries will find in this book an important compendium of fundamental concepts and practical tools for their daily research and activities.

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.

This book provides an overview of historical and contemporary cases of homicidal poisoning. While homicidal poisoning is sometimes thought of as a thing of the past, it continues to be a contemporary problem, and in fact the unknown offender rate for poisoning cases is 20-30 times that of other homicide types in contemporary research, and many poisoners commit serial homicides while going undetected.The author of this important and timely work explores the theoretical bases for understanding homicidal poisoning, the nature of poisons used in homicidal cases, the characteristics of poisoners and their victims, and techniques for detection and prevention. This unique book will be of particular interest to: students of criminology (classes dealing with criminal psychology, and murder investigation); students of the history of crime; criminal justice professionals: attorneys, homicide detectives, forensic pathologists, forensic and clinical toxicologists, and other forensic investigators; and all interested in poisons, poisoners and the detection of poisoning. It has relevance to criminology, law and policing, toxicology and forensic science, the history of crime and detection, and criminal psychology. Endorsements: "A most welcomed addition to the important subject of the criminal poisoner. The author has done a fantastic job of researching the world literature, and distilling it down for the reader. The work is very well referenced, and provides critical information for law enforcement, forensic pathologists, and others, that could be dealing with the criminal poisoner." John H. Trestrail IIIToxicologistLos Lunas, New Mexico USA "Dr Michael Farrell has produced a comprehensive and authoritative work on a most serious but often overlooked aspect of criminal assault - the act of poisoning. In the Criminology of Homicidal Poisoning, Farrell seamlessly weaves together the facts about poisons and their use as an instrument of homicide with the context of the larger issue of murder. By examining the poisoner and the victim, the reader is provided a depth of understanding about how a deadly outcome arose and why the choice was made to employ poison to get the grisly job done. With criminal homicide by poisoning making up a small percentage of known crimes, the danger of insufficient scholarly attention is present. Dr Michael Farrell makes a significant contribution to ensure against this potential. As a homicide researcher, I know Criminology of Homicidal Poisoning will join the works I turn to in understanding the nuances of the how and why of homicide." Dr Richard M. Hough, Sr., Criminology and Criminal Justice and Public Administration Program Coordinator, University of West Florida, US "This comprehensive text links forensic toxicology with criminology, making a solid contribution to both fields. Farrell not only describes how homicidal poisoning fits the most popular criminological theories for why people kill but also examines the nature and lethality of various poisons, identifies trends in poisoning, provides a history, and shows offender traits and victim characteristics. In addition, he discusses issues for investigators and prosecutors who will be taking a poisoning case to trial." Katherine Ramsland Professor of forensic psychology at DeSales University, PennsylvaniaPsychology Today

The field of eicosanoid metabolism and function continues to grow. Synthesis of the prostaglandins from essential fatty acids was first described by Bergstrom and Sarnuelsson in 1964. The thromboxanes were discovered in 1975, the prostacyclins, by Moncada and Vane, in 1976, and the leukotrienes by Samuelsson in 1979. A new class of biologically active arachidonic acid metabolites named lipoxins was announced by Bengt Samuelsson in May 1984. Since that time major advances have been made in the molecular biology of the eicosanoids including the cloning of prostaglandin synthases and 5, 12, and 15-lipoxygenases from several different species, including man. This volume, Prostaglandins, Leukotrienes, Lipoxins, and P AF: Their Mechanism of Action, Molecular Biology, and Clinical Applications contains most of the papers presented in the plenary sessions of the Xlth International Washington Spring Symposium on Health Sciences. The book is divided into six parts, each covering a different aspect of this rapidly expanding field, and contains a total of 42 chapters by an internationally recognized group of authors in each area. Part I contains 11 chapters and covers the molecular biology and enzymology of prostaglandins and leukotrienes. Chapter 1 by the Editor details new mechanisms for the antiinflammatory glucocorticoids involving translational control of the messenger RNA for prostaglandin synthase. Chapter 2 by Yamamoto describes the molecular evolution of two distinct mammalian 12-lipoxygenases.

This detailed volume aims to introduce nanomaterials as a new therapeutic regimen in treating human diseases. Divided into four sections, it explores inorganic nanomaterials, organic nanomaterials, pharmaceutical properties of nanomaterials, and applications of nanomaterials in medicine. Several examples of inorganic and organic nanomaterials are provided to demonstrate how to design and develop nanomaterials for pharmacological purposes. The key pharmaceutical properties, including biocompatibility, tissue interaction, pharmaceutics, and pharmacokinetics of nanomaterials are discussed with a focus on the safety and pharmaceutical considerations of nanomaterials in translational development. The pharmacological applications of nanomaterials are depicted in treating various human diseases, including cancer, cardiovascular diseases, immune disorders, infectious diseases, gastrointestinal disorders, bone diseases, respiratory disorders, and drug delivery. Written for the Methods in Pharmacology and Toxicology series, chapters include the kind of specifics and practical advice that ensures a smooth transition into the lab. Authoritative and enlightening, Nanomaterials in Pharmacology serves as an ideal guide to researchers investigating the potential benefits and risks of nanomaterials in pharmacology in order to avoid the pitfalls and to maximize the potential of this vital field of study.

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 book covers new techniques in protein NMR, from basic principles to state-of-the-art research. It covers a spectrum of topics ranging from a "toolbox" for how sequence-specific resonance assignments can be obtained using a suite of 2D and 3D NMR experiments and tips on how overlap problems can be overcome. Further topics include the novel applications of Overhauser dynamic nuclear polarization methods (DNP), assessing protein structure, and aspects of solid-state NMR of macroscopically aligned membrane proteins. This book is an ideal resource for students and researchers in the fields of biochemistry, chemistry, and pharmacology and NMR physics. Comprehensive and intuitively structured, this book examines protein NMR and new novel applications that include the latest technological advances. This book also has the features of: * A selection of various applications and cutting-edge advances, such as novel applications of Overhauser dynamic nuclear polarization methods (DNP) and a suite of 2D and 3D NMR experiments and tips on how overlap problems can be overcome * A pedagogical approach to the methodology * Engaging the reader and student with a clear, yet critical presentation of the applications

Etienne-Emile Baulieu, the discoverer of neurosteroids, and a panel of distinguished scientists and clinical researchers exhaustively and critically review all facets of neurosteroids involved in behavior, stress, memory, depression, anxiety, aging of the brain, and neurodegenerative diseases. These contributors illuminate the role of neurosteroids in brain development and plasticity and detail their neuromodulatory influence on GABAA, ionotropic glutamate receptors, acetylcholine receptors, sigma receptors, and calcium channels. Clearly pointing the way toward novel pharmaceutical agents that may be of significant therapeutic value, particularly with regard to aging mental functions, Neurosteroids: A New Regulatory Function in the Nervous System offers neurobiologists, psychiatrists, neurosurgeons, pharmacologists, and geriatricians the first comprehensive, state-of-the-art review of these important bioactive molecules.

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.

The Symposium on New Drugs provides for an annual forum for academic investigators, research and development personnel from the pharmaceutical and related health care industries, and members of the Food and Drug Administration to discuss important clinical research issues. The Tenth Annual Symposium on New Drugs addressed the problem of whether it was still appropriate to approve antihypertensive agents soley on the endpoint of lowering cuff blood pressure. The initial discussions at this symposium related to the approaches and methods to studying antihypertensive agents. Dr. William Frishman provided a detailed list of the new approaches to the treatment of hypertension and pointed out the many new concepts that are currently active in the development of many new antihypertensive agents. Dr. William White detailed the growing importance of ambulatory blood pressure monitoring to define hypertension and to determine the change in blood pressure due to pharmacologically active agents. Dr. Jay Cohn pointed out the flaws in using cuff blood pressure and detailed the potential virtues of using vascular compliance to identify patients requiring treatment for hypertension. Dr. Thomas Pickering also discussed the potential value of evaluating changes in left ventricular hypertrophy a finding which identifies high risk patients who need to be included in clinical trials. Dr. Michael Weber detailed the issues and suggested refinements in the approaches to clinical trial designs for antihypertensive agents and Dr. Raymond Lipicky discussed the definition of dose-duration and the role of non-Mem and Peak/Through measurements in defining an antihypertensive drug effect.

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.

There is a high demand for antimicrobials for the treatment of new and emerging microbial diseases. In particular, microbes developing multidrug resistance have created a pressing need to search for a new generation of antimicrobial agents, which are effective, safe and can be used for the cure of multidrug-resistant microbial infections. Nano-antimicrobials offer effective solutions for these challenges; the details of these new technologies are presented here.

The book includes chapters by an international team of experts. Chemical, physical, electrochemical, photochemical and mechanical methods of synthesis are covered. Moreover, biological synthesis using microbes, an option that is both eco-friendly and economically viable, is presented. The antimicrobial potential of different nanoparticles is also covered, bioactivity mechanisms are elaborated on, and several applications are reviewed in separate sections. Lastly, the toxicology of nano-antimicrobials is briefly assessed."

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.

Part B explores protein degradation occuring in vivo during protein synthesis in cells, examines the isolation and purification of proteins, details protein use in organisms, and reviews techniques to enhance protein stability.

At the Mie International Symposium held in Japan in April 1994, leading scientists reviewed recent advances in the understanding of the contractile mechanism in smooth muscle. The present volume collects the papers presented at the symposium, summarizing the latest advances in smooth muscle function and emphasizing important components of the contraction-relaxation cycle. Topics include a discussion of the smooth muscle cell membrane, with emphasis on its ion channels; the regulation of cytosolic Ca2+ levels and the relationship to force in smooth muscle; aspects of the two key regulatory enzymes involved with myosin phosphorylation-dephosphorylation; the molecular basis for pharmacomechanical coupling in smooth muscle; developments in the basic contractile mechanisms involving the crossbridge cycle of tonic and phasic muscle; the role of myosin light chains; and many others. The approach is broad and presents contemporary opinions in pharmacology, physiology, and biochemistry as they relate to smooth muscle function. The book will appeal not only to those working in these disciplines, but to vascular clinicians, obstetric-gynecological physicians, and gastroenterologists as well.

Contents. List of Contributors. Preface. T.J. Mitchell and T.J. Williams: The role of eotaxin and related CC-chemokines in asthma and allergy. Roger J. Davis: Signal transduction by the JNK group of MAP kinases. Marie Chabot-Fletcher: TNF and IL-1 signaling to NF-kB. Anthony M. Manning: Small molecule regulators of AP-1 and NF-kB. Robert T. Abraham: Mammalian target of rapamycin: Immunosuppressive drugs offer new insights into cell growth regulation. Catherine A. Burton, John Boylan, Candy Robinson, Janet Kerr and Pamela Benfield: Constitutive expression of a tumor suppressor leads to tumor regression in a xenograft model. Steven D. Shapiro: Macrophage metalloproteinases in destructive inflammatory diseases. Nancy H. Ruddle: Lymphotoxin in inflammation and lymphoid organ development: Variations on a theme. Steven L. Kunkel, Sem H. Phan, Nicholas W. Lukacs, Cory Hogaboam and Stephen W. Chensue: Chemokine/cytokine biology during the evolution of fibrotic disease. Long Gu, Susan C. Tseng and Barrett J. Rollins: The role of MCP-1 in disease. Lisa A. Beck, Cristiana Stellato, Syed Shahabuddin, Renate Nickel and Robert P. Schleimer: The role of chemokines in allergic diseases of the airways. James Winkler and Ken Tramposch (coordicators): Ninth International Conference of the Inflammation Research Association, November 1-5, 1998: Summaries of workshops and poster discussions. William Williams and Elizabeth Arner (chair persons): Targets in rheumatoid and osteoarthritis. Lawrence Wennogle and Nancy Cusack (chair persons): Signal transduction and regulation of gene expression. James Burke and Floyd Chilton (chair persons): Mediators in inflammation and their enzymes. Denis Schrier and Fandrew Issekutz (chair persons): Cell adhesion molecules and leukocyte trafficking. Robert M. Strieter and David Underwood (chair persons): Pulmonary inflammation, fibrosis, and disease. W. Hunter and E. Turley (chair persons): Angiogenesis, wound repair and skin inflammation. Index.

Recombinant proteins and polypeptides continue to be the most important class of biotechnology-derived agents in today's pharmaceutical industry. Over the past few years, our fundamental understanding of how proteins degrade and how stabilizing agents work has made it possible to approach formulation of protein pharmaceuticals from a much more rational point of view.

This book describes the current level of understanding of protein instability and the strategies for stabilizing proteins under a variety of stressful conditions.

Investigation of the pharmacokinetics and metabolism of human proteins has escalated over the last two decades because of the use of recombinant human proteins as therapeutic agents. In addition, the development and improvement of analytical techniques enabling the detection of minute quantities of proteins in biological matrices have aided this process. In assembling this volume, we sought to provide a state-of-the-art as sessment of the pharmacokinetics and metabolism of protein therapeutics through complete reviews of selected examples. A comprehensive review of all protein therapeutics was not attempted; the majority -of the therapeutic protein classes and crucial scientific issues have been addressed, however. Therefore, we are confident that this volume will provide a useful reference for scientists in this field. The volume has been divided into two general parts. The first part (Chapters 1-3) is composed of general reviews of topics of importance in pharmacokinetic/metabolism studies of proteins: goals and analytical meth odologies, effects of binding proteins, and effects of antibody induction, respectively. The second part (Chapters 4-8) consists of specific, detailed reviews by therapeutic protein class: growth factors and hormones, cyto kines, cardiovascular proteins, hematopoietic proteins, and antibodies, respectively. The editors are grateful to the contributors for the patience, personal sacrifice and perseverance required to complete this volume. BoDDE L. FERRAIOLO MARJORIE A. MOHLER CAROL A. GLOFF ix Contents Chapter 1 Goals and Analytical Methodologies for Protein Disposition Studies Bobbe L. Ferraiolo and Marjorie A. Mohler 1. Introduction ................................................. ."