Pharmaceutical scientists in industry and academia will appreciate this single reference for its detailed experimental procedures for conducting biopharmaceutical studies. This well-illustrated guide allows them to establish, validate, and implement commonly used in situ and in vitro model systems. Chapters provide ready access to these methodologies for studies of the intestinal, buccal, nasal and respiratory, vaginal, ocular, and dermal epithelium as well as the endothelial and elimination barriers.

Volume eight brings up to date several areas important to physicians who care for people with addictive disorders. It deals with the topic of combined alcohol and other drug dependences, and includes chapters on definition of the dependence syndrome, social deviancy and alcohol dependence, and biolo

Antiplatelet therapy is the cornerstone of treatment of ischemic cardiovascular disease and over the last few years spectacular advancements in this field have been recorded. This is the first comprehensive handbook entirely dedicated to all the aspects of antiplatelet therapy. The book is divided into three main sections, pathophysiology, pharmacology and therapy, for a total of 23 chapters. A large group of leading experts from different European countries and from the USA, both from academia and industry, have contributed to the book. Besides a detailed overview on the pharmacology and clinical applications of all the currently used or of the novel antiplatelet agents, innovative approaches (e.g. intracellular signalling as an antiplatelet target, small RNAs as platelet therapeutics, etc.) or unconventional aspects (e.g. pharmacologic modulation of the inflammatory action of platelets are also treated. The book is oriented to both basic investigators and to clinicians involved with research on platelet inhibition or with the clinical use of antiplatelet therapies.

The understanding of the role of dendritic cells (DCs) in immune responses has come a long way since Steinmann and colleagues described these cells in 1972. - tensive research during the intervening period has provided a good understanding of the complexity of the DC system and its pivotal role in immunity. It is also now clearer how different subsets of DCs interact and regulate each other and how DC populations affect the function of other cells of the immune system. The improved understanding of their role in immune response has led to the idea that modulation of DC functions by, for example, pharmacological agents could be used as a pot- tial therapeutic approach in some pathological conditions. The actual applicability and therapeutic potential of all these approaches is yet to be fully demonstrated but nonetheless, animal models of human diseases are proving to be very helpful in the evaluation of manipulated DCs as a new treatment in diseases like cancer, auto- munity or asthma. DCs are integral to the initiation and regulation of immune response (Banchereau et al. 2000). The outcome of antigen presentation by DCs is determined by their maturation status, which can be induced by their interaction with danger signals. To recognise a wide array of pathogen-associated molecular patterns (PAMP), DCs express a number of pattern recognition receptors (PRR) such as Toll-like rec- tors (TLRs) and C-type lectin receptors (CLR) that recognise structural components of pathogens and discriminate between self and non-self molecules.

The young investigator with an idea has to negotiate many institutional, federal, and industrial challenges in order to get a product to market. Nowhere is described the steps in the development of new drugs, diagnos tics, or devices; the person with an idea has nowhere to turn for information and details. The young investigator may understand the elements of basic and clinical research, but ordinarily has no insight into novel ways of finding research funding or how to explore to find the funding opportunities that are available. The young investigator has little knowledge of the mecha nisms to bring an idea through the developmental phases to the market. There are other players in this complex endeavor with whom he or she has no contact, including those from industry, the Food and Drug Administration, and the legal community. Exposure to the philosophy of product develop ment and to procedural information would be useful to the scientific com munity, as would contact with those who have successfully taken an idea to a finished product. A first attempt to do this was the symposium on Idea to Product: The Process, sponsored by Serono Symposia USA and held No vember 17 to 20, 1994, in Washington, D.C. This book comprises the pro ceedings of that meeting. The editors are indebted to the many contributors to this volume, and we are especially grateful to Serono Symposia USA and to Leslie Nies and her staff for their expertise in organizing the symposium."

Recent analyses of drug attrition rates reveal that a significant number of drug candidates fail in the later stage of clinical development owing to absorption, distribution, metabolism, elimination (ADME), and toxicity issues. Lead optimization in drug discovery, a process attempting to uncover and correct these defects of drug candidates, is highly beneficial in lowering the cost and time to develop therapeutic drugs by reducing drug candidate failures in development. At present, parallel synthesis combining with high-throughput screening has made it easier to generate highly potent compounds (i. e. , hits). However, to be a potential drug, a hit must have drug-like characteristics in addition to potency, which include optimal physicochemical properties, reasonable ph- macokinetic parameters, and good safety profiles. Therefore, research tools must be available in drug discovery to rapidly screen for compounds with favorable drug-like properties, and thus adequate resources can be directed to projects with high potential. Optimization in Drug Discovery: In Vitro Methods is a compilation of detailed experimental protocols necessary for setting up a variety of assays important in compound evaluation. A total of 25 chapters, contributed by many experts in their research areas, cover a wide spectrum of subjects including physicochemical properties, abso- tion, plasma binding, metabolism, drug interactions, and toxicity. A good pharmacokinetic profile has long been recognized as an imp- tant drug-like characteristic. Pharmacokinetic parameters are affected by many properties of drug molecules such as physicochemical nature, abso- tion, metabolic stability, and so on.

"Frank discussions of opportunities and challenges point the way to new, more effective drug delivery systems"

Interest in nanomedicine has grown tremendously, fueled by the expectation that continued research will lead to the safe, efficient, and cost-effective delivery of drugs or imaging agents to human tissues and organs. The field, however, has faced several challenges attempting to translate novel ideas into clinical benefits. With contributions from an international team of leading nanomedicine researchers, this book provides a practical assessment of the possibilities and the challenges of modern nanomedicine that will enable the development of clinically effective nanoparticulate drug delivery products and systems.

"Nanoparticulate Drug Delivery Systems" focuses on the rationales and preclinical evaluation of new nanoparticulate drug carriers that have yet to be thoroughly reviewed in the literature. The first chapter sets the stage with a general overview of targeted nanomedicine. The book then explores new and promising nanoparticulate drug delivery systems, including: Lipid nanoparticles for the delivery of nucleic acidsMultifunctional dendritic nanocarriersPolymer drug nanoconjugates

Next, the book presents new opportunities and challenges for nanoparticulate drug delivery systems, including: Clearance of nanoparticles during circulationDrug delivery strategies for combatting multiple drug resistanceToxicological assessment of nanomedicine

Chapters offer state-of-the-technology reviews with extensive references to facilitate further investigation. Moreover, each chapter concludes with an expert assessment of remaining challenges, pointing the way to solutions and new avenues of research.

With its frank discussions of opportunities and challenges, "Nanoparticulate Drug Delivery Systems" sets a solid foundation for new research leading to the discovery and development of better nanomedicines.

This user-friendly resource offers complete and comprehensive coverage of the difficult challenges posed by drug-drug interactions. Over 170 case vignettes illustrate a variety of interactions (DDIs) to provide an unintimidating -- even entertaining -- approach to understanding these issues. Drug-Drug Interaction Primer builds on the author's earlier work, Drug Interactions Casebook: The Cytochrome P450 System and Beyond, and features updated references throughout and 29 new cases that provide such clinical examples as: a patient diagnosed with schizoaffective disorder transitions from haloperidol to aripiprazole with disastrous results; an AIDS patient's trimethoprim-sulfamethoxazole is replaced with warfarin following atrial fibrillation, resulting in ischemic stroke; and a delusional patient on risperidone is placed on phenytoin following seizures, and delusions return. Previous cases have been revised to enhance clarity.

An introduction to core concepts, which includes brief reviews of each enzyme system, brings the reader up to speed on how to think about DDIs and begin to grapple with what might seem like an imposing subject. The vignettes that follow each include a case presentation and an explanation of the mechanism by which the interaction(s) occurred, and each derives from sound clinical evidence -- not merely extrapolations from drug characteristics -- to offer a more realistic understanding of DDIs. Most of the interactions described involve the cytochrome P450 enzyme system; others involve alterations in phase II metabolism and P-glycoprotein functioning, as well as plasma protein displacement effects. The appendices detail most drug-drug interactions between psychotropic agents and contain metabolic pathways and inhibitory and inductive profiles for antidepressants, antipsychotics, and mood stabilizing agents -- as well as tables that detail all known and clinically significant DDIs between pairings of any two agents from these drug classes. An extensive index allows quick reference. Among the book's other features: - Reorganization by medical subspecialty -- psychiatry, internal medicine, neurology, surgery/anesthesia, and gynecology, oncology, and dermatology -- better facilitates clinical application.- Comprehensive tables detail substrates, inhibitors, and inducers for P450, phase II, and P-glycoprotein. - DDIs involving select nonpsychotropic agents such as tobacco, ethinylestradiol, and statins.- Exploration of the paradigm of plasma protein binding mediated DDIs in detail, with cases conveniently indexed.

These cases bring DDIs alive in a way that drier descriptions cannot, and this volume introduces more original material than will be found in other sources. Drug-Drug Interaction Primer is brimming with material that can be put to immediate use, offering insights that will improve any practitioner's skills.

In this book we present recent studies that have been carried out on some widely used medicinal plants. The need for new and alternative treatments stem from the lack of efficiency of existing remedies for certain illnesses. We have compiled information that may be useful to researchers in their quest to develop new drugs.

Extracted from the Drug Abuse Handbook, 2nd edition, to give you just the information you need at an affordable price. Forensic Issues in Alcohol Testing offers concise and focused information specific to the interests of forensic scientists and clinical and forensic toxicologists. It analyzes the acute effects of alcohol intoxication and the methods by which investigators can measure alcohol concentration in blood, urine, and breath. It considers extenuating circumstances affecting acute impairment by detailing the disposition and fate of alcohol in the body as well as the factors influencing absorption, distribution, and elimination. Specific chapters address difficulties in measuring and interpreting post-mortem alcohol concentrations due to poor quality of specimen, sampling site differences, and post-mortem diffusion or synthesis. Recent advances in biochemical testing make it possible to quantitate chronic alcohol ingestion, and the book analyzes the efficacy of these tests as evaluators of dependence or potential for dependence.

Extracted from the Drug Abuse Handbook, 2nd edition, to give you just the information you need at an affordable price.

Pharmacokinetics and Pharmacodynamics of Abused Drugs is a concise and focused volume devoted to the metabolism and measurable effects of drugs on the human body. Beginning with basic concepts and models designed to provide a fundamental understanding of the subject matter, the book details the specifics of absorption, distribution, and elimination pathways and rates of commonly abused drugs. It analyzes the effects of drug use on human performance including response time, memory and recall, logical and cognitive processes, as well as physiological changes. Packed with data and comparative studies, this handy volume considers the effects of marketed and prescription medications as well as illicit drugs including opioids, cannabis, cocaine, methamphetamine, MDMA, ketamine, nicotine, and LSD. Containing 29 figures and tables and extensive references, this is a must-have resource for the influence of drug use and abuse on human physiology and performance.

Research into the processes of tolerance and sensitization has escalated at a substantial rate in recent years, presumably because of the fundamental importance of understanding the long-term, as opposed simply to the initial, acute effects of drugs. The rapid of such research in recent years is documented c1early by growth the editors in the introductory chapter to this text. However, despite the fact that there is a very large amount of literature concemed with the effects of long-term drug treatment, there is, to the best of our knowledge, no published text that has ever attempted to integrate some of the many diverse findings that have been made in this area. Basic research has uncovered a num ber of different mechanisms by which tolerance and sensitization to drugs can develop. Such mechanisms are of very different types, involving psychological behavioral, metabolic, neuronal, and subcellular processes. Because of the complexity of each of these different types of mechanisms, with few exceptions, individual re searchers usually tend, understandably, to concentrate on their own specific areas of expertise, paying relatively little attention to rele vant research occurring in other areas. Consequently, they neglect or simply ignore the important question of the relative importance of the specific mechanism that they are studying, and the related question of the possible interrelationships that may exist between different mechanisms for the production of tolerance and sensitiza tion."

Tamoxifen has persisted as a widely accepted and administered drug for almost 25 years. Following the many scientific papers and books on the subject, it has remained a very intriguing substance. This, perhaps, is the reason for another monograph on Tamoxifen. It is regrettably true that overviews, even when up to date after exhaustive research - the shibboleth of our cultures -, rapidly lose relevance with the passage of time. Scientists can sometimes be pictured as deep sea divers, who plunge into the unknown in search of a hitherto unknown world. Their descent is exciting, but eventually they must come up for air and integrate their experiences with others who also had to resurface. This book intends to collect and, where possible, to collate recent, but sometimes seemingly unrelated information. To quote Stephane Mallarme: "Everything in the world exists to end up in a book." Even if this is a tad cynical, it might not be far from the truth. If a little knowledge is a dangerous commodity, one can also add - tongue in cheek - that a vast amount of knowledge can be truly hazardous. It is likely that what might seem as entangled data is confusing, especially for those satisfied with the comfortable interpretation of Tamoxifen as an antiestrogen which has long been found insufficient. The complexity of its mechanisms and effects defies simple explanations and may even seem capricious, but only because of our ignorance.

This volume thoroughly covers HIV-1 antiretrovirals currently in clinical use, together with their advantages and limitations. HIV-1 inhibitor resistance is discussed in detail, and critical assessments as to what will be required of future antiretrovirals in order to halt viral replication, reduce viral resistance, and alter the state of viral latency are presented. Experts at the forefront of HIV-1 research provide overviews of approaches from the fields of virology, chemical biology and structural biology for obtaining small molecule inhibitors that target viral regulatory and structural components at multiple points in the viral lifecycle. The individual chapters will appeal to scientists and clinicians alike.

This book was tbe result of a symposium beld at tbe American Cbernical Society meeting in Miami Beacb, Florida, September 10-15, 1989. The symposium was jointly sponsored by Tbe Society for Economfc Botany and tbe American Cbernical Society Food and Natural Product sub division. Tbere were five speakers. During tbe social sessions (mostly over drinks in abotel room), it became obvious tbat, regardless of tbe discipline, we were all speaking tbe same language. Yet, prior to tbe symposium, only a few of tbe participants knew one anotber. We decided to expand tbe symposium into a book. The book would, we boped, accomplish for otbers wbat we bad discovered in ourselves. That is, the field of Natural Products is broad, but similar in techniques and approach, ancient but modern, and bas been and continues to be extremely valuable to humankind. We wanted the book to serve as an introductory text for courses and as a reference work for the future. We also determined to include the structure of every chemical in the chapter where it was mentioned so the reader would not have to find the structure somewhere else or to try and deduce the structure from the chemical name. Little did we know what an undertaking these goals would be or the time this would take.

The clinical microbiology laboratory is often a sentinel for the detection of drug resistant strains of microorganisms. Standardized protocols require continual scrutiny to detect emerging phenotypic resistance patterns. The timely notification of clinicians with susceptibility results can initiate the alteration of antimicrobial chemotherapy and improve patient care. It is vital that microbiology laboratories stay current with standard and emerging methods and have a solid understanding of their function in the war on infectious diseases. Antimicrobial Susceptibility Testing Protocols clearly defines the role of the clinical microbiology laboratory in integrated patient care and provides a comprehensive, up-to-date procedural manual that can be used by a wide variety of laboratorians. The authors provide a comprehensive, up-to-date procedural manual including protocols for bioassay methods and molecular methods for bacterial strain typing. Divided into three sections, the text begins by introducing basic susceptibility disciplines including disk diffusion, macro and microbroth dilution, agar dilution, and the gradient method. It covers step-by-step protocols with an emphasis on optimizing the detection of resistant microorganisms. The second section describes specialized susceptibility protocols such as surveillance procedures for detection of antibiotic-resistant bacteria, serum bactericidal assays, time-kill curves, population analysis, and synergy testing. The final section is designed to be used as a reference resource. Chapters cover antibiotic development; design and use of an antibiogram; and the interactions of the clinical microbiology laboratory with the hospital pharmacy, and infectious disease and control. Unique in its scope, Antimicrobial Susceptibility Testing Protocols gives laboratory personnel an integrated resource for updated lab-based techniques and charts within the contextual role of clinical microbiology in modern medicine.

Focused more specifically on the recent advances in applications of various metals and their complexes used in biomedicine, particularly in the diagnosis and treatment of chronic diseases. The editors give equal importance to other key aspects such as toxicological issues and safety concerns. The application of metals in the biomedical field is highly interdisciplinary and has a broad appeal across all biomedical specialties. Biomedical Applications of Metals is particularly focused on covering the role of metals in medicine and the development of novel therapeutic products and solutions in the form of alternative medicines, and some topics on Indian traditional medicine i.e., "Ayurveda". In Section I, the book discusses the role of metals in medicines and include chapters on nanoparticles, noble metals, medical devices, copper. selenium, silver, and microbial pathogens; while Section II includes topics on metals toxicity including heavy metals, carcinogens, cancer therapy, Bhasma's and chelating agents used in Ayurveda, and biochemical and molecular targets including actions of metals. These new and emerging concepts of applications of metals in medicine, their crucial role in management of microbial resistance, and their use in the treatment of various chronic diseases is essential information for toxicologists, and clinical and biomedical researchers.

The formation of drug policy is a complex phenomena influenced by a multi tude of sources. Among others, these influences include historical factors, contemporary public opinion regarding the nature and magnitude of drug use and abuse, the portrayal of illicit drugs and drug use in the media, and lobbying efforts by special interest groups (e. g. , The Drug Policy Foundation), including government agencies (e. g. , the Justice Department and law enforcement). An additional source of influence are the activities of specialists directly engaged in studying drug use and treating drug dependence. This includes individuals involved in drug treatment, anthropological and cultural studies, policy analy ses, basic psychological and pharmacological research, research on the epide miology of drug use and dependence, and research on prevention. This influ ence by specialists might be usefully distinguished from those influences first mentioned for two reasons: First, studies of drug use and dependence attempt to uncover empirical generalizations about drugs, and second, because these findings are empirical, there is a hope that they guide, at least to some extent, the actions of other forces that more directly determine drug policy. Psychology as an empirical discipline has long been interested in the use of psychoactive drugs. At the level of basic science in psychopharmacology, a most important contribution has been the demonstration that drugs of abuse function as reinforcers and thus enter into the same psychological processes as do other appetitive stimuli.

From the President of the American Society of Addiction Medicine Recent Developments in Alcoholism (Volume 10) is a major contribution to the literature of addiction medicine. This volume, 'ru.cohol and Cocaine: Similarities and Differences," contains an impressive collection of chapters from the basic research, epidemiological, and clinical research perspectives, as well as articles that address the relative policy issues and clinical application and patient care concerns. It also sends a message to those who would still distinguish between alcohol and drugs, or legal and illegal drugs. In the research laboratory, in the intentions and behavior of the user, and by the clinician, such distinctions have never been upheld. The first section, "Clinical Pathology," includes chapters on the role of alcohol in cocaine dependence, dual-diagnosis empirical and developmental humanistic approaches, and on neuroendocrine and catecholamine levels in humans during administration and withdrawal of cocaine and alcohol, emer gency room evaluation of cocaine-associated neuropsychiatric disorders, and clinical and pharmacological interactions of alcohol and cocaine. These chap ters, written by authors who are preeminent in their fields, offer a broad perspective to both the researcher and the clinician on relevant issues in clinical pathology. ."

Western Medicine as seen today has a strong scientific basis in its development. The pathogenesis of most diseases and their symptomatology and physical signs are well studied and understood. The management of patients is based on firm understanding of these disease processes. In contrast, Traditional Chinese Medicine came about through the experience of many generations of practitioners over thousands of years. Undoubtedly, many of these treatments have proved to be effective in their own way, however, firm scientific basis is still lacking.

While most Western Medicine advocates control of disease by eradication of pathogens and surgical removal of diseased organs as in the case of cancer, Traditional Chinese Medicine seeks to improve resistance against disease. There is probably a great wealth of therapeutic value in Traditional Chinese Medicine, which has not been discovered or explored fully. By combining the knowledge of both Western and Traditional Chinese Medicine, one might be able to improve the results of efficacy of treatments and the survival of patients. The integration of Medicine from East and West will take time to evolve and will need interested physicians from different parts of the world to work closely together to realize such a possibility.

This book is an attempt to bridge the medical world of two great and ancient civilizations in their approach to the treatment of disease. It is informative with a detailed account of the history of medical development. It is highly recommended for those medical practitioners from both East and West who are interested to explore alternative medicine and research new areas of the medical frontier.

In the two decades since the elusive "slow reacting substance of anaphylaxis" (SRS-A) was identified as a product of the action of the 5-lipoxygenase enzyme on arachidonic acid, it has been well established that the leukotrienes are key mediators of both alIergy and inflammation. Their release by alIergen or other challenge has been demonstrated in the lungs of asthmatic subjects, and measurement of urinary leukotriene concentrations in such patients has been shown to be a valuable, non invasive indicator. Significant progress has been made towards the characterization of the leukotriene receptor subtypes, exemplified by the cloning of the LTB4 receptor earlier this year. Coupled with this there has been a continued elucidation of signal transduction mechanisms underlying receptor activation. Consequent upon these advances has been the development of potent antagonists of the CysLT receptor, J and both these and inhibitors of leukotriene biosynthesis have entered clinical practice in the therapy of asthma. In this clinical setting antagonists of the CysLTJ receptor have been shown to be an effective therapy in chronic asthmatics, against antigen- and exercise-induced bronchoconstriction, and in aspirin-intolerant asthmatics. The advent of this new class of agents promises to change the way in which asthmatic patients are currently treated."