Bøger i Progress in Inflammation Research serien

In the last ten years, major strides have been made in defining the presence and role of inflammation in atherosclerosis as well as in injury to the tissues that occurs after episodes of ischemia and reperfusion.

The importance of this cytokine release is evident from both diagnostic and thera peutic (mostly experimental) studies, and the action of cytokines may be the key to our understanding of the pathophysiology of the sepsis syndrome.

Chronic obstructive pulmonary disease (COPD) ranges amongst the commonest diseases in the world. The relentless progression of the disease causes a pressing need for a better understanding of and therapies for COPD. This volume provides state-of-the-art information on the pathophysiology of COPD including an outlook on new therapies.

Numerous improvements in our understanding of the mechanisms that underlie neuropathic pain states have come from the development of animal models, most of which involve partial peripheral nerve injury.

From the basic science to potential and approved clinical applications the most recent data in the rapidly growing field of bone morphogenetic proteins (BMPs) are summarized in this topical volume. Distinguished scientists present reviews on a range of scientific topics, including biochemistry, biology, molecular biology and preclinical animal studies on spinal fusion, cartilage repair, craniofacial and dental reconstruction using BMPs, as well as approved clinical applications in human bone non-unions.This book provides a resource not only for experts in the field, but also for undergraduate students, newcomers and clinicians worldwide, given that the use of BMPs in orthopedic reconstruction has been already approved in Europe, Australia, Canada and the USA.

Pain and inflammation are inextricably linked phenomena. The observation that chemical mediators with combined pro-inflammatory, algesic and/or hyperalgesic activity occur at the site of inflammation is fundamental not only to our present understanding of the inflammatory process but also to our attempts to devise clini­ cally useful anti-inflammatory therapies. Over a hundred years ago it was recognised that primary sensory neurones play a crucially important "dual" role in inflammation. By affecting the transfer of infor­ mation from peripheral nociceptors to the spinal cord, a subpopulation of sensory nerves {"pain fibres"} initiate algesia and hyperalgesia, whose sensations are then modified and fine-tuned in the central nervous system. Equally important is the release from the peripheral terminals of sensory neurones of neuropeptides, the acute effects of which are observed as changes in microvascular tone and perme­ ability leading to neurogenic inflammation. Over the last decade it has become increasingly clear that this view of the func­ tion of sensory nerves is somewhat over-simplified. For example, the mechanisms underlying hyperalgesia may, in certain circumstances, be mimicked in other condi­ tions such as the hypersensivity associated with asthma. Furthermore, it has become increasingly evident that over a longer time period the release of neuropeptides from peripheral sensory nerve endings may also have modulating effects on inmune cells and that this may be relevant to chronic inflammatory disease and possibly also to inflammatory hyperalgesia.

This volume will be of great value to all those researchers in the area of the inflam matory response, notably academics, clinicians and members of the pharmaceutical industry.

Over the past ten years, a number of cytokines and growth factors have proven to be as effective therapeutics.

Dalip J. S. Sirinathsinghii and Ray G. Hill Merck, Sharp & Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, UK There remains a distinct medical need for new pain therapies. Therefore, it is not surprising that in recent years there has been a major research initiative in both aca­ demic and pharmaceutical laboratories to identify novel pain targets and to devel­ op novel analgesic drugs. It is clear from numerous studies that the NMDA recep­ tor plays a major role in the transmission ofnociceptive information and it has been a subject of extensive investigation over the last decade exploiting the advances of molecular pharmacology and molecular neuroanatomy. As a consequence there has been a rational approach by several laboratories to develop receptor subtype-spe­ cific NMDA antagonists in order to avoid the wide range of side-effects seen with non-selective NMDA ion channel antagonists such as ketamine. This volume brings together contributions from experts in various technological disciplines who have contributed immensely to NMDA receptor research and advanced our understanding of the subunit composition of the NMDA receptor complex, its pharmacology and distribution, its interaction with other neurochemi­ cal systems and the effects on behaviour of NMDA antagonists in rodent models and in the clinic. In consideration of these advances and the prospects of novel NMDA receptor antagonists in the near future for the treatment of pain, this vol­ ume is very timely.

There is now considerable preclinical evidence that glutamate acting via the NMDA receptor is involved in the transmission of nociceptive information and in the triggering mechanisms for hyperalgesia and allodynia. This book gives information on molecular biology, physiology and pharmacology of NMDA receptors.

For some years, international guidelines on the management of asthma have stressed the importance of early intervention with anti-inflammatory drugs to prevent acute asthma exacerbations and to avert chronic inflammatory damage to the airway.

These chapters provide a unique vantage point from which to examine this question, as the summarized work ranges from evolutionary approaches across diverse species, to the basics of the immune response, to the effect of cytokines on peripheral and central nervous system sites, to therapeutic potential in humans.

Many new antileukotriene drugs are now marketed as antiasthma drugs and represent the first new drugs in this field since the 1970s.

Whilst systems such as these to a mathematician would provide the basis for a chaotic response, one is forced to marvel how, for all stages of an inflammatory reaction, this system appears exquisitely controlled, making therapeutic manipula tion both possible and, to some extent, predictable.

Airways inflammation is a complex biological phenomenon resulting from the recruitment and activation of numerous cell types. This book provides a collection of valuable reviews on the major inflammatory cells involved in airways disease and examines the pharmacology of current anti-inflammatory drugs used in the treatment of airways disease.

In November 1998 many of the key leaders of new drug discovery for inflammatory diseases gathered at Hershey, Pennsylvania for the 9th International Conference of the Inflammation Research Association.

The allergic skin diseases which will be discussed are atopic dermatitis, being the chronic inflammatory skin disease with the highest prevalence, allergic contact dermatitis with special focus on contact dermatitis from cosmetics, being the most frequent cause of contact dermatitis and occupational contact dermatitis.

It addresses different therapeutic intervention possibilities for new drugs, such as the cellular source of cytokines, specific receptors which induce cytokine synthesis, intracellular regulators of cytokine gene induction and expression, secretion and activation of cytokines, cytokine receptors and signalling pathways from these receptors.

This book contains reviews by a renowned group of clinicians and scientists, which consider in great depth the potential involvement of neurogenic inflammation in the pathogenesis of migraine and inhibition of this putative mechanism as a possible mode of action of antimigraine medications. The authors carefully consider current and future potential therapeutic approaches for the abortive as well as preventive treatment of migraine. The pioneering work by Professor Michael A. Moskowitz's group at Harvard gave rise to the "neurogenic hypothesis" of migraine pathogenesis and to an intel­ lectual framework for many aspects of migraine research through a detailed phar­ macological characterization of the trigeminovascular system. This knowledge then spurred detailed research worldwide into the roles of the dural vasculature, trigem­ inal nerve fibers, and sensory neuropeptides, such as substance P and calcitonin gene-related peptide, in migraine. Similar in-depth investigations have not been made of the role of the seventh cranial parasympathetic nerves but this area war­ rants further study because of its potential for interactions with the trigeminovas­ cular system and its clear involvement in cluster headache.

Heat shock proteins (HSP) have received ample interest by immunologists over recent years. Since then, the raised presence of immunity to HSPs in virtually all conditions of inflammation, including autoimmune diseases, transplant rejection and atherosclerosis, has emphasised the critical significance of immunity to HSPs in inflammatory diseases.

This book focuses on the salient features of the biology of Bone Morphogenetic Proteins and the advances in our understanding of their structure and function and of downstream signaling, as well as their governance in systems biology from bone and dentin to kidney, cancer, diabetes, iron homeostasis and angiogenesis, including rare musculoskeletal disorders. BMPs, also referred to as growth and differentiation factors, are members of the TGF-beta superfamily and are highly conserved from fruit flies to mammals and are responsible for the formation of practically every organ during embryo development and involved in adult tissue injury and repair. BMPs establish their extracellular gradient by interacting with their respective antagonists and regulate their function through SMAD-dependent down-stream signaling effector genes.This volume is aimed at scientists and professionals dealing with metabolic disorders, nutrition, systems biology diseases, rare musculoskeletal conditions, and disorders related to iron metabolism, including anemia of chronic disease, hereditary hemochromatosis and beta thalassemia.

Discusses the potential involvement of neurogenic inflammation in the pathogenesis of the migraine headache and the inhibition of this mechanism as a possible mode of action of anti migraine medications. This book also addresses the impact of migraine on a personal and societal level, the presentation, pathogenesis, and treatment of migraine.

Especially the past two decades have seen renewed interest in the vasculitides. Drawing from their work in rheumatology, nephrology, internal medicine, connective tissue disease and clinical immunology, they present new concepts in classificiation, diagnosis and pathophysiology of the vasculitides.

Since the discovery of the bone morphogenetic proteins (BMPs) more than 15 years ago, there has been an unpredicted explosion of both basic scientific discoveries and clinical reports on their use from institutions all over the world.

The purpose of this volume in the Progress in Inflammation Research series is to provide the biomedical and clinical researcher with a state-of-the-art insight in the role of cytokines in joint inflammation and joint destruction.

Such coverage, as presented in this volume, may help further understanding and bring new approaches to therapeutics.The first section of the book discusses inflammatory mechanisms, studied in cellular and animal studies.

Combinatorial chemistry in conjunction with High Throughput Screening (HTS) is revolutionizing the drug discovery process.

Gene therapy for inflammatory diseases is a new , burgeoning field of medicine. As an up-to-date, timely book written by the leaders in the field, this volume will appeal to both medical and graduate students, medical reseachers, members of the biotechnology community, physicians and all those interested in this latest frontier of molecular medicine.

The importance of this cytokine release is evident from both diagnostic and thera peutic (mostly experimental) studies, and the action of cytokines may be the key to our understanding of the pathophysiology of the sepsis syndrome.

Chronic obstructive pulmonary disease (COPD) ranges amongst the commonest diseases in the world. The relentless progression of the disease causes a pressing need for a better understanding of and therapies for COPD. This volume provides state-of-the-art information on the pathophysiology of COPD including an outlook on new therapies.