After the discovery of endogenous NO formation in the late '80s and the 1998 Nobel Prize in Physiology or Medicine, many researchers and physicians again became interested in the NO/sGC interaction and cGMP-dependent signaling. This book is an enthusiastic celebration of cyclic guanosine monophosphate (cGMP) and amply illustrates the importance of this field of science to patients and the way in which the field has evolved. It is exclusively devoted to this exciting and important signaling molecule, addressing all recent advances in understanding guanylate cyclase regulation, NO/sGC interactions, cGMP effector mechanisms and their pathophysiological and pharmacological implications. Particular attention will also be given to clinical applications of the novel cGMP-elevating drugs which are on the horizon, thus spanning the continuum from basic science to clinic.

As the drug discovery process shifts more and more toward specifically targeting pathways and molecules, model systems continue to increase in importance, and the mouse, with its versatility, ease of use, and remarkable similarity to the human genome, has clearly risen to the forefront of animal model studies. In Mouse Models for Drug Discovery: Methods and Protocols, experts in the field present some background for those less familiar with mice as experimental model platforms as well as a collection of techniques involving general methods as well as specific disease topics such as type 1 and 2 diabetes, cardiovascular disease, arthritis, skin disorders, cancer, the use of behavioral models for depression and anxiety, neurodegenerative diseases, neuromuscular diseases, and infectious diseases. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and notes on troubleshooting and avoiding known pitfalls.

Authoritative and easy-to-use, Mouse Models for Drug Discovery: Methods and Protocols will stimulate those not familiar with the power of the mouse and its potential for the drug discovery process, and it will encourage the development of new models and new ways to utilize existing models in order to further the use of this dynamic animal in this vital field."

The goal of this work is summarize the contribution that insertional mutagenesis has made to our understanding of cancer. A variety of insertional mutagens are presented that have been used to study a variety of tumor types in several model organisms. In addition, the impact of insertional mutagenesis in several gene therapy trials is discussed along with strategies to avoid such complications in future clinical trials.

Neuropeptide Y (NPY) is a ubiquitous and important messenger in the nervous system, with a wide range of physiological roles. It is involved in the body energy balance and is one of the most potent stimuli of food intake known. NPY also acts to regulate central and peripheral autonomic functions.
This book, written by academic and industrial experts in the field, links the most recent basic experimental knowledge about NPY and its receptors with areas of clinical importance.
This book will be of interest to those working in all areas of research affected by NPY, such as food intake and energy homeostasis, cardiovascular regulation and G-protein-coupled receptors, as well as those interested in the development of drugs as NPY targets.
Key Features
* The hypothalamic role of NPY and its relationship with eating disorders and diabetes
* The sympathetic nervous system role of NPY and its involvement in cardiovascular disorders
* Characterization of NPY receptor types and their brain distribution, molecular biology and pharmacology
* Development of peptide and non-peptide receptor antagonists

Antibiotics are truly miracle drugs. As a class, they are one of the only ones that actually cure disease as opposed to most drugs that only help relieve symptoms or control disease. Since bacteria that cause serious disease in humans are becoming more and more resistant to the antibiotics we have today, and because they will ultimately become resistant to any antibiotic that we use for treatment or for anything else, we need a steady supply of new antibiotics active against any resistant bacteria that arise. However, the antibiotics marketplace is no longer attractive for large pharmaceutical companies, the costs of development are skyrocketing because of ever more stringent requirements by the regulatory agencies, and finding new antibiotics active against resistant strains is getting harder and harder. These forces are all combining to deny us these miracle drugs when we need them the most. I provide a number of possible paths to shelter from this perfect storm.

Conceptually unsavoury, airway mucus is vital to homeostasis in the respiratory tract. In contrast, when abnormal, mucus contributes significantly to the pathophysiology of a number of severe bronchial diseases, including asthma, chronic bronchitis and cystic fibrosis. This volume provides wide ranging and in-depth coverage of the scientific and clinical aspects of airway mucus. It commences with introductory chapters which address the biochemical and molecular biological basis of airway mucus and continues with comprehensive coverage of the various physiological and rheological aspects of respiratory secretions. The clinical aspects of the topic are then considered, with chapters discussing the involvement of mucus secretions in bacterial infection and in hypersecretory diseases of the airway. The volume concludes with a discussion of the therapeutic aspects of the topic, both in terms of the possible approaches to the treatment of mucus hypersecretion and the interaction of these drugs with airway mucus. Written by leading experts in the field, each contribution provides a comprehensive review of its particular subject. Reflecting the latest advances in this important area of respiratory research, this volume will be of great interest to scientists and clinicians working in the field of airway secretions and related areas.

Mycotoxins, from the Greek "mukes" referring to fungi or slime molds and toxin from the Latin "toxicum" referencing a poison for arrows, have earned their reputation for being potentially deleterious to the health and well being of a consuming organism, whether it be animal or human. Unfortunately, mycotoxins are a ubiquitous factor in the natural life cycle of food producing plants. As such, control of the potential impact of mycotoxins on food safety relies heavily upon accurate analysis and surveys followed by commodity segregation and restricted use or decontamination through processing. The purpose of this book is to provide the most comprehensive and current information on the topic of mycotoxins and assuring food safety. Chapters represented in the book reflect such diverse topics ranging from occurrence and impact, analysis, reduction through processing and plant breeding, toxicology and safety assessments to regulatory perspectives. Authors represent a range of international perspectives.

Specialist Periodical Reports provide systematic and detailed review coverage of progress in the major areas of chemical research. Written by experts in their specialist fields the series creates a unique service for the active research chemist, supplying regular critical in-depth accounts of progress in particular areas of chemistry. For over 90 years The Royal Society of Chemistry and its predecessor, the Chemical Society, have been publishing reports charting developments in chemistry, which originally took the form of Annual Reports. However, by 1967 the whole spectrum of chemistry could no longer be contained within one volume and the series Specialist Periodical Reports was born. The Annual Reports themselves still existed but were divided into two, and subsequently three, volumes covering Inorganic, Organic, and Physical Chemistry. For more general coverage of the highlights in chemistry they remain a 'must'. Since that time the SPR series has altered according to the fluctuating degree of activity in various fields of chemistry. Some titles have remained unchanged, while others have altered their emphasis along with their titles; some have been combined under a new name whereas others have had to be discontinued. The current list of Specialist Periodical Reports can be seen on the inside flap of this volume.

The three years since our last conference in San Francisco have again seen a dramatic expansion of the number of antivirals either licensed or in the late stages of clinical trials. d4T is now licensed for HIV infection, famciclovir and the oral pro-drug of acyclovir, valacyclovir, are now licensed for VZV infections in some countries. Moreover. oral ganciclovir, cidofovir, and sorivudine are not far behind. Clinical trials with the second-site reverse transcriptase inhibitors and the protease inhibitors for HlV infection are proceeding rapidly and on a broad scale, and the preliminary results would suggest that several of these classes of drugs will be licensed as well. Despite this optimism, however, there is increasing evidence that antiviral-resistant strains of pathogenic viruses will be a significant problem, perhaps especially with therapy of HIV infection, and there remains a desperate need for improved drugs (with either improved efficacy or decreased toxicity, or both) for CMV and HIV infections. This book is the edited proceedings of the Fourth Triennial Conference on Antiviral Chemotherapy, held in San Francisco, in November 1994. The conference was sponsored by the University of California, San Francisco, and co-sponsored by the International Society for Antiviral Research (ISAR), the Macfarlane Burnet Centre for Medical Research in Melbourne, Australia, and the Australian National Centre for HIV Virology Research. The conference had been organized to present an overview of the field of antiviral chemotherapy.

Genetic Algorithms in Molecular Modeling is the first book available on the use of genetic algorithms in molecular design. This volume marks the beginning of an ew series of books, Principles in Qsar and Drug Design, which will be an indispensible reference for students and professionals involved in medicinal chemistry, pharmacology, (eco)toxicology, and agrochemistry. Each comprehensive chapter is written by a distinguished researcher in the field.
Through its up to the minute content, extensive bibliography, and essential information on software availability, this book leads the reader from the theoretical aspects to the practical applications. It enables the uninitiated reader to apply genetic algorithms for modeling the biological activities and properties of chemicals, and provides the trained scientist with the most up to date information on the topic.
. Extremely topical and timely
. Sets the foundations for the development of
computer-aided tools for solving numerous
problems in QSAR and drug design
. Written to be accessible without prior direct
experience in genetic algorithms

This detailed volume brings together leading practitioners in the freeze-drying community to address recent progress, not only in new analytical tools and applications of the data derived in cycle design but also in the manufacturing of lyophilized products in the healthcare sector - whether these be therapeutics, vaccines or diagnostic products - and indeed the equipment to deliver this scale of freeze-drying. Areas of focus include analytical and formulation issues, process monitoring and control, as well as post-lyophilization analysis. Written for the Methods in Pharmacology and Toxicology series, chapters include the type of expert advice that leads to superior results in the lab. Authoritative and practical, Lyophilization of Pharmaceuticals and Biologicals: New Technologies and Approaches serves as an ideal guide for researchers working in or just seeking an update on this rapidly changing field.

Over the past ten years, a number of cytokines and growth factors have proven to be as effective therapeutics. While these products have certainly established recombinant biologics as a major pharmaceutical growth sector, the continued interest in this class of drugs arises from the fact that today we have a far better understanding of the human immune response, both at a cellular and molecular level. This has resulted in a more methodical characterisation of these factors which has given clinical researchers an opportunity to plan Phase 1 clinical trials that can provide substantial information on the activity of the cytokine in humans. Currently, a great deal of effort is also being channelled into identifying cytokines from the various DNA databases. Our major objective for this book is to profile cytokines that have been recently identified. The therapeutic potential of these cytokines based on their known properties will be discussed by the authors. The main aim of this book is to provide...

This book provides the most up-to-date review of the simian virus 40 (SV40) minichromosome as a model for the mammalian chromosome in studies of DNA replication. It focuses on disruption of DNA replication by anticancer drugs and DNA-damaging agents. There is a strong emphasis on the unique advantages of SV40 as an experimental system for the analysis of these classes of anticancer drug mechanisms. The new high-resolution gel electrophoresis methods for the analysis of SV40 DNA replication are covered in detail to aid readers in designing and interpreting similar experiments.
Key Features
* Presents unique advantages of SV40 as an experimental system for the study of classes of anticancer drugs
* Details new high-resolution gel electrophoresis methods for the analysis of SV40 DNA replication
* Provides details to help the reader design and interpret similar experiments

A comprehensive, state-of-the-art review of our current understanding of the molecular and structural biology of 5-HT receptors and their potential use for drug discovery. The authors describe the anatomical, cellular, and subcellular distribution of 5-HT receptors and demonstrate a powerful approach to elucidating their physiological role using knockout mice in which the 5-HT receptors were deleted. They also review our understanding of the physiological role(s) of 5-HT receptors based mainly on studies performed in genetically engineered mice. Highlights include discussions of the behavioral phenotypes of 5-HT receptor knockout animals, the molecular biology and pharmacology of 5-HT receptors, and insights into the complexity of 5-HT receptor signal transduction.

This volume comprehensively covers the multiplicity and diversity of mechanisms underlying patient resistance to currently approved anti-cancer drugs, including tyrosine kinase inhibitors and monoclonal antibodies, blockers of growth factor receptors and their downstream pathways, which play essential functions in cancer progression. Each chapter will cover a specific group of targets and the cognate drugs, along with molecular modes of innate and evolving resistance.

380 years ago, in the year 1614, Ubbo Emmius transplanted the gene ofscience from Ostfriesland into the education genome ofthe city ofGroningen as devel oped by Regnerus Praedinius. He thereby founded the University ofGroningen. It is with great pleasure that the Faculty of Medicine as one of the founding faculties ofour University, welcomes you to this 19th International Symposium ofBloodTransfusion, whichwill coverthe themeofHereditaryDiseasesandtheir relation to Transfusion Medicine, where cell expansion, gene transfer and gene therapy are the read thread. Since the earlydays there has beena specificand sincere interest in inborn errors ofmetabolism and hereditarydisorders. This interest has resulted in a structured research, diagnostic and counselling facilities, and therapeuticapproaches where various disciplines within our faculty work closely together with groups from related faculties of the University of Groningen, as well as other national and international scientific institutions. The field of inborn errors, genetic abnormalities and mutations, and hereditary diseases covers a broad gamma of extremely interesting and exciting scientific aspects, whichrangefrom clearphysicalaberrationstomolecularanalysisofgenes and genomes, coding areas and amino acid sequences. It is intriguing to realise that the balance of life seemingly depends on the position or presence of one single molecule as a part ofthe total complex ofgenetic information in the cell."

Rapid advances in computer science, biology, chemistry, and other disciplines are enabling powerful new computational tools and models for toxicology and pharmacology. These computational tools hold tremendous promise for advancing science, from streamlining drug efficacy and safety testing, to increasing the efficiency and effectiveness of risk assessment for environmental chemicals. Computational Toxicology provides biomedical and quantitative scientists with essential background, context, examples, useful tips, and an overview of current developments in the field. Divided into four sections, Volume I covers a wide array of methodologies and topics. Opening with an introduction to the field of computational toxicology and its current and potential applications, the volume continues with 'best practices' in mathematical and computational modeling, followed by chemoinformatics and the use of computational techniques and databases to predict chemical properties and toxicity, as well as an overview of molecular dynamics. The final section is a compilation of the key elements and main approaches used in pharmacokinetic and pharmacodynamic modeling, including the modeling of absorption, compartment and non-compartmental modeling, physiologically based pharmacokinetic modeling, interspecies extrapolation, and population effects. Written in the successful Methods in Molecular Biology (TM) series format where possible, chapters include introductions to their respective topics, lists of the materials and software tools used, methods, and notes on troubleshooting. Authoritative and easily accessible, Computational Toxicology will allow motivated readers to participate in this exciting field and undertake a diversity of realistic problems of interest.

Progestogens are a class of steroid hormones that bind to and activate the progesterone receptor. This book is a guide to the use of progestogens for clinicians. Beginning with an overview of structure, biochemistry and classification, the following chapters discuss methods of administration, pharmacokinetics, metabolism and the physiological actions of progesterone. The remaining sections of the book cover clinical usage guidelines for progestogens, their role in contraception, side effects and contraindications. The book concludes with a chapter offering guidance on prescription writing and detailed references. Key points Guide to progestogens for obstetricians and gynaecologists Provides step by step detail on structure, classification, and pharmacokinetics Includes clinical usage guidelines, side effects and contraindications Features chapter on prescription writing

Immunopharmacology represents the boundary between the immune system and chemical mediators of the inflammatory and neuroendocrine responses. The subject as applied to the respiratory system embraces most of the common non-malignant lung diseases of which asthma and allied disorders are the most prevalent. An understanding of the underlying mechanisms of the disorders provides rationale for prevention and drug treatment as well as creating opportunities for novel drug development. This volume embraces all of these principles and should enable the reader to become rapidly updated in an area of medical importance.
*
* Focuses on aspects of disease pathogenesis that are common to a variety of lung disorders.
* Includes coverage of the mechanisms of asthma - origin, progression, and novel therapeutic interventions.
* This volume is another in the "Systems" section of the Handbook of Immunopharmacology.

Specialist Periodical Reports provide systematic and detailed review coverage of progress in the major areas of chemical research. Written by experts in their specialist fields the series creates a unique service for the active research chemist, supplying regular critical in-depth accounts of progress in particular areas of chemistry. For over 90 years The Royal society of Chemistry and its predecessor, the Chemical Society, have been publishing reports charting developments in chemistry, which originally took the form of Annual Reports. However, by 1967 the whole spectrum of chemistry could no longer be contained within one volume and the series Specialist Periodical Reports was born. The Annual Reports themselves still existed but were divided into two, and subsequently three, volumes covering Inorganic, Organic, and Physical Chemistry. For more general coverage of the highlights in chemistry they remain a 'must'. Since that time the SPR series has altered according to the fluctuating degree of activity in various fields of chemistry. Some titles have remained unchanged, while others have altered their emphasis along with their titles; some have been combined under a new name whereas others have had to be discontinued. The current list of Specialist Periodical Reports can be seen on the inside flap of this volume.

The first comprehensive book to cover all aspects of the last 25 years of PACAP (pituitary adenylate cyclase activating polypeptide) research, this book contains contributions from virtually all the leading researchers in the field, and addresses some of the following topics: evolutionary aspects of PACAP, distribution and occurrence of PACAP and its receptors, hormonal effects of PACAP, intracellular signaling, effects on cellular proliferation and differentiation, protective effects of PACAP, behavioral effects of PACAP, developmental aspects of PACAP, other physiological effects of PACAP (cardiovascular, thermoregulatory), human studies, drug design, metabolism and transport. This compendium can serve as an important reference for researchers and students in PACAP research and can also be a thorough introduction for those in related fields.

Drinking alcohol can, in rare instances, provoke a temporary psychotic often violent reaction called pathological intoxication. Although it was medically identified in 1869, pathological intoxication has been an enigma to the law for over a century, primarily because the actual medical and psychiatric aspects of the concept have not been adequately explained before. But, as the authors of this volume point out, it is crucial for the defense attorney and the prosecutor to understand whether pathological or ordinary intoxication is involved in a particular case because pathological intoxication furnishes the basis of important and perhaps decisive defense strategies beyond those which derive from ordinary intoxication. This interdisciplinary study provides the first in-depth exploration of both the medical and psychiatric facts underlying the phenomenon of pathological intoxication and explores the suitability of various defense theories.

Written especially for practicing criminal defense lawyers, public defenders, prosecutors, and forensic psychiatrists, the volume begins by examining the clinical and experimental evidence of pathological intoxication. In subsequent chapters, the authors alert the attorney to the indications that a defendant should be examined for possible pathological intoxication and include hard-to-find medical sources of support for the concept to persuade courts and prosecutors of its legitimacy. A series of chapters thoroughly explores all the relevant legal defense strategies available in pathological intoxication cases including the defense of automatism, the law of insanity, involuntary intoxication, and diminished capacity and extreme mental and emotional disturbance. Throughout, the authors incorporate both domestic and foreign literature relating to pathological intoxication. The inclusion of ample case examples as well as a wealth of medical and psychiatric data make this book a major contribution to our understanding of both the phenomenon of pathological intoxication and its implications for legal defense strategy.