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.

Highlighting 15 selected chiral structures, which represent candidate or marketed drugs, and their chemical syntheses, the authors acquaint the reader with the fascinating achievements of synthetic and medicinal chemistry.

The book starts with an introduction treating the discovery and development of a new drug entity. Each of the 15 subsequent chapters presents one of the target structures and begins with a description of its biological profile as well as any known molecular mechanisms of action, underlining the importance of its structural and stereochemical features. This section is followed by detailed discussions of synthetic approaches to the chiral target structure, highlighting creative ideas, the scaling-up of laboratory methods and their replacement by efficient modern technologies for large-scale production. Nearly 60 synthetic reactions, most of them stereoselective, catalytic or biocatalytic, as well as chiral separating methodologies are included in the book.

Vitomir Sunjic and Michael J. Parnham provide an invaluable source of information for scientists in academia and the pharmaceutical industry who are actively engaged in the interdisciplinary development of new drugs, as well as for advanced students in chemistry and related fields.

Each volume of Advances in Pharmacology provides a rich collection of reviews on timely topics. Emphasis is placed on the molecular basis of drug action, both applied and experimental.
Conjugation reactions have long been associated with the detoxification of xenobiotics. Recent studies suggest that Phase II reactions are an important mechanism for the bioactivation of xenobiotics.
This special volume of Advances in Pharmacology features a two-color dust jacket.
Key Features
* Summarizes the most recent information on:
* Xenobiotic conjugation
* Drug toxicity, hypersensitivity, and targeting
Chemical carcinogenesis
* Glutathione-, sulfate conjugate-, and glucuranide conjugate-dependent toxicity
* Bioactivation and bioconversion

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.

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.

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.

Primary care clinicians are called on to care for adolescents in a time with increasing pharmacologic agents that are available in the management of these patients. The emphasis in this book is on the current pharmacologic treatment of common medical disorders in adolescents. Selected topics of practical relevance in adolescent medicine are covered. The goal of this book is to provide a succinct and practical guide specifically written for practicing physicians and allied health professionals who work with adolescents.

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.

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."

During the past fifty years, thousands of natural products have been isolated from plants, fungi, and bacteria. Apart from intense searches by pharmaceutical companies for medicinals and the concentrated effort mounted by the National Cancer Institute, many of these have not been tested in biological systems. The major reasons for this appear to be, at least, twofold. First, individual researchers looking for biologically active natural products will often isolate only small amounts of material sufficient to determine a structure and calculate the specific activity for their particular bioassay systems: insufficient funds preclude re-isolating the compound unless industrial potential is foreseen. Second, the difficulty with which original structures were proved prior to 1972. This required the isolation of relatively large quantities of a natural product and there followed extensive degradation, elemental analyses of the parent and its fragments, then synthesis, piece by piece, of the molecule. All this took time and energy. No wonder that when the structure was proved the chemist was enervated. And coupled to this was the fact that many chemists were not trained to test their materials in biological systems. In contrast, today a natural product can be isolated, its mass and molecular formula determined and, if there is some serendipity, crystals may be obtained for single crystal x-ray analysis. If conditions are near perfect, it is possible to isolate and identify a novel compound in a month.

Topical and transdermal drug delivery systems (TDDs) have several advantages over traditional drug delivery methods, as they can be less invasive, more sanitary, more cost-effective, and may result in better patient compliance. TDDs play a significant role in therapeutics with a variety of preparations and approaches designed by expert formulation scientists. This volume integrates a wide variety of case studies, research, and theories to reveal their diversity and capture the novel approaches of transdermal and topical drug delivery employed by developers and content experts in the field. It provides an abundance of important information and state-of-the-art research on topical and transdermal drug delivery systems and addresses the basics of drug delivery systems, strategies to enhance permeation across membranes, and formulation and evaluation of diverse dosage forms. The volume presents an evaluation of the pros and cons of conventional drug delivery systems against TDDs and discusses the nuances of micro- and nano-systems in TDDs. The extraordinary packages of nano systems (vesicular systems, polymeric nanoparticles, nanoemulsion and dendrimers) are broadly discussed, and their applications are reviewed through a transdermal route. The book looks at TDDs and the main nanoparticles used in skin diseases and lesions of the aging, such as psoriasis, vitiligo, cancer, lesions of the aging and others. Chapters also discuss polymeric micelles in topical and transdermal delivery; microneedles; emulsion, nanoemulsion and microemulsion; TDDs in pulmonary drug delivery systems; nanoencapsulated nasal drug delivery systems; skin sensitivity and irritation testing for transposing transdermal drug delivery systems; and regulatory aspects of drug development for dermal products. Topical and Transdermal Drug Delivery Systems: Applications and Prospects will be a valuable resource for pharmaceutical scientists and researchers, industry professionals, and academicians and students of the pharmaceutical and biomedical sciences.

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

Beads made from Egyptian faience have been excavated from grave deposits (c. 4000-3100 BC), together with beads of glazed steatite (a soft rock) and of se- precious stones such as turquoise, carnelian, quartz, and lapis lazuli. Information on these and many more ancient beads used for ornaments and jewelry, ritual ceremonies, as art artifacts and gifts for amorous women throughout history, and descriptions of the raw materials (e. g. , glass, bone, precious and other stones) and manufacturing technologies used for their production can be located in many references. Many books are devoted to the description of beads that are not of water-soluble polymer origin, techniques for their production, their art, value, and distribution, re?ecting the wealth of information existing in this ?eld of science and art. On the other hand, there are no books fully devoted to the fascinating topic of hydrocolloid (polymeric) beads and their unique applications. A few books c- tain scattered chapters and details on such topics, while emphasizing the possibility of locating fragments of information elsewhere; however, again, there is no book that is solely devoted to hydrocolloid beads and their versatile applications. In the meantime, the use of water-soluble hydrocolloid beads is on the rise in many ?elds, making a book that covers both past and novel applications of such beads, as well as their properties and ways in which to manipulate them, crucial.

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.

Leading researchers are specially invited to provide a complete understanding of a key topic within the multidisciplinary fields of physiology, biochemistry and pharmacology. In a form immediately useful to scientists, this periodical aims to filter, highlight and review the latest developments in these rapidly advancing fields.

This volume is dedicated to the topic of cyclic GMP. Chapters include discussions on the guanylyl cyclase and phosphodiesterase isoenzyme families for cyclic GMP synthesis and hydrolysis, cyclic GMP-dependent protein kinases, and various hormones and ligands that regulate cyclic GMP formation and/or metabolism. Several chapters also deal with some of the effects of cyclic GMP on other second messengers such as calcium ion transport and smooth muscle relaxation. Some clinical studies with cyclic GMP and atrial natriuretic peptide are also discussed. The last chapter raises many important questions in the field that remain to be addressed.
Key Features
* Isoforms of guanylyl cyclase and phosphodiesterase isoenzyme families for cyclic GMP synthesis and hydrolysis
* Cyclic GMP-dependent protein kinase
* Hormones and ligands that regulate GMP formation and/or metabolism
* Effects of cyclic GMP on other second messengers and some functions such as smooth muscle relaxation and ion transport
* Clinical studies with cyclic GMP and atrial natriuretic peptide
* Important questions and experiments for the future

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.

In my professional career as a pharmaceutical scientist, I have been involved with severalaspectsofthe drugdevelopmentprocessfrompre-INDto commercialization and, somehow, I usually found myself coming back to a stability-related issue. The stability area seemed to draw my utmost interest because in my day-to-day work, my opportunities involved more than one product, and none of the issues were the same.Eachsituationposedchallengesthatusuallyrequiredanexerciseofjudgment, an understandingof regulations, a knowledgeof science, a graspof compliance, and an appreciation of common practices. Sinceearly2000, Ihavealsobeeninvolvedwithseveraltrainingopportunitiesand I struggled to ?nd good, concise, practical resources, one of which I could just hand to a new scientist who wishes to gain a greater understanding of stability sciences. In addition, I encountered the same questions posted over and over on different stability best practices discussion forums. As a book lover, I also have a good collection of technical books. Unfor- nately, most of the stability related volumes are outdated. Many of these materials are theoretical and do not contain much practical information. I understand that the pharmaceutical industry during this period is quite volatile, and guidelines are changingrapidlywhileregulatoryagenciesareworkingcloselywiththepharmac- tical industryto accommodatethese changes;however, thefundamentalinformation continues to remain quite the same, just as current Good Manufacturing Practices (cGMP) continue to be the standard industry practice. Therefore, I hoped to ass- ble a practical handbook to ?ll this v

This book gathers international and national reports from across the globe on key questions in the field of antitrust and intellectual property. The first part discusses the application of competition law in the pharmaceutical sector, which continues to be a focus for anti-trust authorities around the world. A detailed international report explores the extent to which the application of the competition rules in the pharmaceutical sector should be affected by the specific characteristics of those products and markets (including consumer protection rules, the need to promote innovation, the need to protect public budgets, and other public interest considerations). It provides an excellent comparative study of this complex subject, which lies at the interface between competition law and intellectual property law. The second part of the book gathers contributions from various jurisdictions on the topic of "What rules should govern claims by suppliers about the national or geographic origin of their goods or services?" This section presents an international report, which offers an unparalleled comparative analysis of this topic, bringing together common themes and contrasting the various national provisions dealing with indications of origin, amongst other things. The book also includes the resolutions passed by the General Assembly of the International League of Competition Law (LIDC) following a debate on each of these topics, which include proposed solutions and recommendations. The LIDC is a long-standing international association that focuses on the interface between competition law and intellectual property law, including unfair competition issues.

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."

This book summarizes the recent advances for the understanding of circadian clock system in the regulation of drug metabolism and pharmacokinetics. Basic knowledge in the field of circadian clock and pharmacokinetics are systemically introduced to make it easier for readers to understand the entire book's contents. The rhythmic expression of DMEs (drug-metabolizing enzymes) and transporters are summarized, and the underlying mechanisms thereof (i.e., regulation by circadian oscillators) are discussed. Typically, evidence for the DME- and transporter-mediated chronopharmacokinetics, chronotoxicity and chronoefficacy are highlighted in this book.