The inducible isoforms of the enzymes cyclooxygenase (COX 2), nitric oxide synthase (iNOS) and heme oxygenase 1 (HO-1) have generated great interest as possible therapeutic targets in inflammation. This book is the first publication to address the importance of all three enzymes and the consequences of their interactions to the inflammatory process. The book brings together overviews by leading researchers in the field of the current status of knowledge of COX, NOS and HO in inflammation. These overviews cover a series of new concepts in the mechanism of inflammation. Topics include inducible enzyme involvement in inflammatory processes including the role in vascular permeability, leukocycte migration, granuloma formation, angiogenesis, neuroinflammation and algesia. New findings from transgenic animal models are reviewed. Other chapters address the importance of these enzymes in inflammatory disease states including rheumatoid arthritis, atherosclerosis and multiple sclerosis. The possibility of selective inhibitors or inducers of COX, NOS and HO, and their use in the clinic is discussed. The subject matter of this book is of interest to rheumatologists, pathologists, pharmacologists, neuroscientists and anyone with an academic interest in the mechanisms of inflammation.

More than 70 years have elapsed since U. S. von Euler and I. H. Gaddum dis- covered an unidentified depressor substance in the brain and gut. The effects of the powdery extracts were marked as 'P' on the kymograph tracings, and the nondescript name of 'substance P' still carries the breath of this adventurous period. In the 1960s, substance P returned in another disguise, staging as a hypothalamic peptide that causes copious salivary secretion (see chapter by F. Lembeck and I. Donnerer). This time, though, the mysterious substance was tracked down by S. E. Leeman and her collaborators as an undecapeptide, after it had eluded its identification for some 40 years. Substance P turned out to be the mammalian counterpart of a family of peptides which had been extracted from amphibian and nonvertebrate species and which had been given the name 'tachykinins' by V. Erspamer. Soon novel members of this peptide family were discovered, and in mammals substance P was joined by neurokinin A and neu- rokinin B. The presence of tachykinins in frog skin as well as in venoms and toxins of microbes and arachnids raises the possibility that these peptides re- present an old system of biological weapons that have been transformed to a particular messenger system in mammals.

An increasing number of exercise scientists are applying their skills collaboratively (with medics and physiotherapists) to clinical populations and investigating the effects of exercise in relation to wide-ranging clinical, pathophysiological and psycho-social outcomes. The book is aimed at final year Undergraduate and Master's level students of Exercise Science, who are interested in working with clinical populations such as cancer patients. Many university Sport and Exercise Science courses in the UK and USA now have modules which are focused on exercise for health, and cover aspects of exercise science which are appropriate for clinical populations. The book would also be a very valuable resource for Undergraduate and Postgraduate Physiotherapy courses and a very useful resource for students of Exercise Science and Physiotherapy, as well as practitioners working with cancer patients.There are an increasing amount of research opportunities for exercise scientists who are interested in working with clinical populations. Furthermore, a considerable amount of Government and Charity research funding is being targeted at active lifestyles and this is helping to generate a new culture of collaboration between exercise scientists and medics. Hence, it is highly likely that an increasing number of students from Sport and Exercise Science courses will pursue careers within the clinical realm in the future. Practicing exercise therapists, clinical exercise physiologists and physiotherapists would also find lots of useful up-to-date knowledge to support their evidence-based clinical practice. This book would also be of interest to informed readers who are themselves undergoing or recovering from cancer treatment.

In Handbook of Drug Monitoring Methods: Therapeutics and Drug Abuse, authors discuss the different analytical techniques used in todaya (TM)s practice of therapeutic drug monitoring and drugs of abuse as well as alcohol testing with relevant theory, mechanism, and in-depth scientific discussion on each topic. This volume is the perfect handbook and quick reference for any clinical laboratory, allowing clinicians to find the potential source of a false-positive or a false-negative result in the daily operation of a toxicology laboratory. At the same time, this book can also be used as a reference for medical technologists, supervisors, laboratory directors, clinical chemists, toxicologists, and pathologists to find in-depth cause of a potential interference and what tests can be ordered to circumvent such problem. The volumea (TM)s first half focuses on various issues of therapeutic drug monitoring. Additional chapters cover analysis of heavy metals, alcohol testing, and issues of drugs of abuse testing. These chapters are written by experts in their relative sub-specialties and also by the editor. Comprehensive and timely, Handbook of Drug Monitoring Methods: Therapeutics and Drug Abuse is the ideal text for clinicians and researchers monitoring alcohol and drug testing and other important tasks of toxicological laboratory services.

Due to the rapid and steady growth of available low-cost computer power, the use of computers for discovering and designing new drugs is becoming a central topic in modern molecular biology and medicinal chemistry. In Computational Drug Discovery and Design: Methods and Protocols expert researchers in the field provide key techniques to investigate biomedical applications for drug developments based on computational chemistry. These include methods and techniques from binding sites prediction to the accurate inclusion of solvent and entropic effects, from high-throughput screening of large compound databases to the expanding area of protein-protein inhibition, toward quantitative free-energy approaches in ensemble-based drug design using distributed computing. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters include introductions to their respective topics, reference to software and open source analysis tools, step-by-step, readily reproducible computational protocols, and key tips on troubleshooting and avoiding known pitfalls. Thorough and intuitive, Computational Drug Discovery and Design: Methods and Protocols aids scientists in the continuing study of state-of-the-art concepts and computer-based methodologies.

The book explores cutting-edge strategies to overcome proteasome inhibitor resistance, including the second generation 20S proteasome inhibitors, novel combinational therapies, and new targets in the ubiquitin-proteasome pathway (e.g., ubiquitin E3 ligases, deubiquitinases, 19S proteasomal ATPases, histone deacetylases, oxidative stress and proteotoxic stress pathways and pharmacogenomic signature profiling) in resistant cancer cells. The mechanisms of action and resistance of proteasome inhibitors, such as bortezomib and carfilzomib in human cancers, including multiple myeloma, mantle cell lymphoma, acute leukemia, and solid tumors are explored in depth in this volume.

This timely volume unveils the most current discoveries of the mechanisms behind proteasome inhibitor resistance, which will help illuminate the future of cancer therapies.

Scientific interest in regulatory T cells has revived during the last decade. Initially described in the early seventies as suppressor T cells, the concept of suppressor/regulatory T cells went through turbulent times during the eighties when molecular analysis failed to identify putative suppressor genes. The constructive and elegant cellular experiments on regulatory T cells during the nineties, initiated by Shimon Sakaguchi and co-workers, however have brought these cells back into the limelight. Nowadays, regulatory T cells are regarded as essential components of the immune system, and several different subsets of regulatory T cells have been described. Considerable regulatory function has been attributed to the CD4+CD25+ T cell subset. These cells act by suppressing adaptive and possibly also innate immune responses thereby maintaining or restoring the balance between immunity and tolerance. The suppressive effects of CD4+CD25+ regulatory T cells are cell-contact dependent but a role for soluble factors, particularly in vivo, has been suggested as well.
The aim of this book is to bring together recent developments and viewpoints in the field of CD4+CD25+ regulatory T cells and to discuss the potential use of regulatory T cells in immunotherapy of inflammatory diseases. By linking data on regulatory T cells from experimental models with recent findings from the clinic, this topical book will be of interest to immunologists and other biomedical researchers as well as clinicians that are interested in regulation and manipulation of the immune response during (chronic) inflammatory disease.

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This book illustrates the current state-of-the-art in histamine research, with a focus on the appropriate methodologies to investigate the pharmacological properties and the therapeutic exploitation of HRs and their ligands. In addition, the range of techniques described provides an introduction to complementary cross-methodological disciplines beyond these fields. This multi-disciplinary approach is required to define the 'decision gates' that determine the development of more effective and safer therapeutic options for many forms of highly prevalent and debilitating diseases, such as asthma, dementias, dermatitis, and arthritis. Written for the Methods in Pharmacology and Toxicology series, chapters concentrate on practical, hands-on protocols from experts in the techniques. Authoritative and thorough, Histamine Receptors as Drug Targets seeks to aid pharmacologists, biochemists, drug discovery researchers, molecular biologists, chemists, toxicologists, lab scientists, medical doctors, principle investigators, research scientists, lab directors and technicians, as well as graduate students around the world in pursuing the study of this vital scientific area.

Today, most people use prescription medications. Every year, the multi-billion dollar pharmaceutical industry produces new medicines that treat everything from arthritis to AIDS, from high cholesterol to depression. But, despite recent controversies regarding the safety of drugs, consumers know little about the medications that they ingest and inject. How are these new medicines invented? How do consumers know that drugs are safe and effective? How are they tested? Who regulates their production - and who watches the regulators? How do drug companies produce the vast quantities needed for the marketplace, and why do they market their drugs as they do? The New Medicines leads the reader through the maze of the modern drug industry - from bench to bedside - and provides consumers with a step-by-step understanding of how new medicines are created, approved, marketed, and sold. In addition to explaining how drugs reach the medicine cabinet, the author - an experienced researcher and teacher - provides the scientific and business background for understanding the current controversial issues surrounding new medicines, such as:

• The rise and fall of the COX-2 inhibitors, Vioxx and Celebrex, and the process by which they were invented, approved, and re-evaluated.
• The saga of the cancer drug Erbitux and its creator, the company Imclone, made famous as the centerpiece of the Martha Stewart insider-trading scandal
• The strengths and weaknesses of the approval process of the Food and Drug Administration
• The controversial new marketing techniques of the pharmaceutical industry

Withtherecentlyperceivedincreaseinincidenceofautismandtherealizationthat "autism"mayactuallybe"autisms"withsubsetsofaffectedindividuals,researchers have been pursuing the possibility that there may be multiple etiologies for the disorder.Althoughmostautismstudieshavefocusedongeneticsandadvancedn- roimaging,thereisapaucityofresearchaimedatdeterminingtheneurochemical basisofautism.Identifyingcoreneuralsubstratesorkeybiomarkersisessentialto understandingthemechanisticbasisthatmayinpartunderlie"autisms."Alterations inmolecules,proteins,receptors,andsynapticelementsaresomeofthecontrib- ingsubstratesthatcouldresultinaltereddevelopmentalprocesses,changedsynaptic function,andaberrationsinconnectivity.Itisnowapparentthatmultiplebrainareas are affected in autism, and neuropathological defects have been described within corticalandsubcorticalnetworks.Althoughrecentprogresshasbeenmadeinid- tifyingsomeofthegenesthatmayunderliethedisorder,muchattentionhasalso beengiventoepigeneticand/orenvironmentalfactorsthatmaycontributetosubsets ofautisticindividuals. The contributors to this book were hand selected because of their expertise in their respective ?elds. Individually each chapter presents a unique perspective into the clinical, developmental, neurochemical, and/or physical chemical basis of autism. The contributing authors summarize current research ?ndings in their respective areas and also present novel ideas and propose hypotheses and p- sible mechanisms that may be operative during development and the potential consequencesofhavingdefectsinspeci?cmolecules,receptors,orgenes. Thesubtitle"FromMoleculestoMinicolumns"wasinsertedbecauseofmuch recent attention given to alterations in the basic organization of mini- or mic- columns of neurons in cerebral cortical areas in autism. These especially include prefrontalcorticalareasthatundergoanovergrowthduringearlypostnataldevel- mentinmanyindividualswithautism.Tothisend,theworldrenownedDr.Alan Peters,theneuroanatomistthatoriginallydescribedmini-ormicro-columnaror- nizationinthecerebralcortex,wasrecruitedtowriteachapterinthisbookgiving hisexpertperspectiveontheissueinautism. The book begins with highly respected clinician, Dr. Margaret L. Bauman, DirectoroftheLADDERSclinicintheBostonarea,withaclinicalandmedicalp- spectiveofautismdiscussingetiologies,clinicalpresentation,earlyidenti?cation, vii viii Preface advancementsinmedicalcare,andassociateddisorders. Inthechapter"TheMale Prevalence in Autism Spectrum Disorders: Hypotheses on its Neurobiological Basis",ItalianresearchersDrs.FlavioKellerandLilianaRutapresentneuroch- ical hypotheses as the basis for the predominance of male prevalence in autism discussing the possible roles of estrogen, testosterone, oxytocin, and vasopressin in the organization of brain circuits and hemispheric specialization. Psychiatrist Dr. Ricardo Vella relates neuropathologies in autism, in the limbic and cereb- lar regions, to speci?c behaviors and presents a developmental perspective and hypotheses regarding emotional and attachment behaviors in autistic individuals.

Topics covered in this volume include pheromone reception in mammals, elucidation of mammalian bitter taste, synaptic modulation in pain pathways, the vertebrate phototransduction cascade, and amplification and termination mechanisms.

This book provides BoNT treatment menus for symptom-oriented therapy in 14 different disease categories.Each chapter starts with a brief description of the disease and its current treatment followed by an evidenced-based upon the published assertions of the Therapeutic Subcommittee of the American Academy of Neurology. Each chapter includes case histories from editor's vast experience of over 25 years with BoNT therapy and description of injection techniques enhanced by illustrative figures. Botulinum Toxin Treatment in Clinical Medicine includes an additional introductory chapter that discusses molecular structure, mechanism of action, toxin serotypes, immunogenicity and safety issues. Meanwhile, a concluding chapter provides information on potential future application of these toxins' for treating symptoms of other specific diseases.

This book, the proceedings of a Falk Workshop on `Topical Steroids in Gastroenterology and Hepatology', held in Berlin, Germany, on 14 June 2003, critically discusses the current role of budesonide in gastroenterology, hepatology, surgery and oncology and focuses especially on potential new indications for the use of budesonide. A number of smaller clinical studies and anecdotal case reports with impressive clinical effects are reported in patients with gastrointestinal, hepatic, oncological and surgical problems. In addition, the use of budesonide for the treatment of distal ulcerative colitis and ileocolonic Crohn's disease is evaluated with respect to its role in an evidence-based management of IBD. Finally, as clinical experience with the use of budesonide is increasing, safety issues and the side-effect profile of budesonide is addressed.

Hallucinogens: A Forensic Drug Handbook is a comprehensive reference for everyone involved in the identification, investigation, and forensic analysis of hallucinogenic drugs. The text begins with a review of the history of these drugs and their abuse, and then takes an in-depth look at the many different types of hallucinogens, their chemical make-up, how they affect users, how they are manufactured and distributed, and how they can be detected and analyzed.
Hallucinogens covers the most commonly abused drugs such as LSD, MDMA ("Ecstasy"), and PCP ("Angel Dust"), as well as many lesser-known chemical substances that cause similar effects. Chapters have been contributed by leading analysts and investigators around the world, and are highlighted with numerous illustrations. This unique handbook will serve is a cross-disciplinary source of information for forensic toxicologists, law enforcement officers, and others involved in the fight against drugs.
* Brings together comprehensive information on hallucinogenic drugs in one convenient source
* Covers everything from abuse of these drugs to pharmacology, effects, forms, manufacturing methods, distribution, and forensic analysis
* Contains numerous illustrations, chemical structures, and analytic spectra for each drug
* Includes contributions from many of the world's leading investigators and analysts

Adverse events in patients caused by medical management are a serious and grossly underreported public health problem. One patient in ten entering hospital will suffer an adverse event of impairment, disability or death. This book is a major comprehensive examination of the incidence and causes of adverse events. Using data obtained from hospitals within the United Kingdom, United States and other developed countries, it examines the risk factors leading to errors, the human and financial costs, and the scope to reduce errors. In particular, it focuses on the need for a critical reappraisal of undergraduate teaching and clinical tuition. All healthcare professionals throughout primary and secondary care, including clinicians, managers and policy makers, and patient and carer groups, can benefit from reading this book. It identifies possible solutions and how adverse events and medication errors can be reduced, resulting in improved patient care.

A remarkable spectrum of novel immunoreceptors sharing related immunoglobulin-like domains and signaling potential has been identified in recent years. These receptors have attracted widespread interest because they resemble the TCR, BCR, and FcR complexes in their ability to serve as activating or inhibitory receptors on the cells that bear them. Moreover, they are well positioned to affect both innate and adaptive immunity. The full range of ligands for these new receptor families is still not known, and understanding of their physiological roles is far from complete. This volume is the first attempt to summarize and highlight all known aspects of immunoglobulin-like receptors, providing a topical overview of the roles and characteristic features of the immunoglobulin-like receptors and related molecules in the immune system. Researchers in immunology, molecular biology, cell biology, clinical medicine, and pharmacology will find this book invaluable.

Currently, there are tremendous advances being made in understanding the basic science of both the structure and function of botulinum neurotoxins. This knowledge is opening up opportunities in regard to both therapeutic uses and treatment and protection options for civil and bio-defense applications. This volume fully evaluates the status of neurotoxin research and exploitation with a focus on clinical application. The book is a multi-authored collection of chapters written by the leading authorities responsible for the current scientific and clinical research that is advancing the understanding and exploitation of the neurotoxins and is both up to date and authoritative.

As governments seek to mitigate the cost of state-subsidized healthcare, branding in the pharmaceutical industry has become a critical issue. Drugs companies must change their methods of communication and distribution--focusing more on their direct relationship with the consumer. This requires fundamental changes in consumer behavior, access to information, freedom of choice, and value for money. Brands and brand values will play a leading role in this process, as has been seen with products such as Prozac and Viagra. This book by Interbrand Newell and Sorrell, the world's leading branding consultancy, provides cutting-edge thinking on this area and lessons for anyone involved in brand development and management.

This volume discusses the latest advancements and technologies used in cancer drug resistance research. Cancer Drug Resistance: Overviews and Methods contains chapters that cover topics such as: studying the mechanics of resistance to DNA damaging therapeutic drugs; studies to delineate the role of efflux transporters; expression of drug transporters; resistance to targeted therapies in breast cancer; the role of microRNAs in current pancreatic cancer treatment; and cancer exosomes as mediators of drug resistance or clinical and molecular methods in drug development and the use of bioinformatics in the management of cancer drug resistance data. Written in the highly successful Methods in Molecular Biology series format, chapters include overviews of the main issues in cancer drug resistance and the respective mechanisms, as well as introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Cancer Drug Resistance: Overviews and Methods, is a valuable resource to researchers, oncobiologists and clinical oncologists or anyone else who is interested in the study of cancer and its drug resistances.