Literally thousands of papers have been published on nitric oxide over the past ten years. The voluminous literature regarding the incredible range of chemical and biological effects of nitric oxide and reactive nitrogen oxide species, RNOS, may present a tangle of confusing information to the researcher.
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.
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.
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.
It discusses the contribution of occupational exposures to chemical and biological agents to the burden of asthma in adults, powerful approaches like the use of apprentices studies, which include young individuals, naive with regard to occupational exposures, and diagnostic criteria for work related and work aggravated asthma.
Cardiomyopathy is one of the most frequent causes of heart failure. It is often associated with inadequate heart pumping or other heart function abnormalities. This volume, written by a leading expert, focuses on inflammatory CM, belonging to the Dilated Cardiomyopathies (DCMi).
This book summarizes the most advanced technical aspects covering all steps for a thorough application of microarrays to inflammation topics - from sample generation to data analysis. The book will help a researcher or clinician to plan, perform and analyze or to critically review microarray experiments related to inflammation research.
This much-needed text develops current knowledge on the mechanisms of angiogenesis at the molecular and cellular levels as they relate to inflammation, including acute and chronic inflammation, neurogenic initiation, and the role of the multiple cellular components that comprise inflammation.
Despite tremendous advances in the understanding of the sensory nervous system which have accompanied the recent explosive growth of the neurosciences, rema- ably few innovative medicines directed towards pain and inflammation are ava- able.
The accumulation of white blood cells is a hallmark of inflammation. The penetra tion through the vessel walls and the infiltration around the inflammatory stimulus is a complex process which involves active adherence and directed migration of the inflammatory cells. Chemotactic factors stimulate both adherence and migration. Technical tools such as the Boyden chamber [1] made it possible to study leukocyte migration in vitro. This technique allows differentiation between migration direct ed towards a chemotactic stimulus and non-directed migration. Until a decade ago only two naturally occurring molecules had been clearly iden tified as potent chemotactic attractants of neutrophilic granulocytes. They were the split product of the fifth complement component C5a [2] and the arachidonic acid metabolite leukotriene B4 [3]. In 1986, a novel human monocyte-derived chemo taxin attracting neutrophilic granulocytes with a similar potency was found [4]. This report was quickly confirmed by several groups [5-8]. The new factor was purified, cloned and sequenced [9, 10]. The term "interleukin 8" (IL-8) replaced the various names proposed previously [4-8]. Sequence data revealed that IL-8 belonged to a large family of chemotactic cytokines, now called "chemokines" [11]. Four subfamilies were distinguished on the basis of the number and position of the first cysteine residues. They are desig nated accordingly as C, CC, CXC and CX C chemokines [11-13]. The number of 3 human chemokines identified so far is close to 40 [11-13].
In recent years, the area of pharmacotherapy of GI inflammation has witnessed important progress, with new drugs and therapeutic approaches being introduced. The volume reviews the pharmacotherapy of selected gastrointestinal inflammatory conditions chosen on the basis of their clinical importance and/or the areas where important and exciting progress has been made recently. Besides discussing current pharmacotherapy to treat the most important GI inflammation conditions, the book also indicates possible future therapeutic avenues likely to become available in a few years.The book is of interest to various sectors of the scientific community ranging from clinicians to pharmacologists and from biochemists to microbiologists, who will find it a useful tool for their clinical practice and research activity.
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.
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.
Arachidonic acid (AA) and other 20 or 22-carbon polyunsaturated fatty acids (PUFAs) are precursors of lipid mediators of inflammation known as eicosanoids. These mediators are critical in disease processes and in regulating normal cell function. Remodeling is important in maintaining homeostasis and in regulating cell function by dictating how PUFAs are converted to lipid mediators of inflammation. Thus, PUFA remodeling is a critical process in the biosynthesis of a multitude of mediators, and understanding this process will unravel better therapeutic targets for controlling inflammatory diseases such as asthma and Alzheimer¿s disease.AA metabolism is described in an integrated context linking the remodeling processes with the biosynthesis of mediators and diseases. By following the movement of the substrate (AA), the volume describes how upstream biosynthetic pathways influence the formation of lipid mediators of inflammation, showing the metabolic interrelationship between all AA-derived mediators.
Gene therapy for inflammatory diseases is a new , burgeoning field of medicine. Edited by the undisputed pioneers of this area of research, this volume is the first devoted to its topic. It contains thirteen chapters, each written by leaders in their respective fields, that summarize the state of the art in developing novel, gene based treatments for inflammatory diseases. As well as providing an introduction to the basic concepts of gene therapy and the use of naked DNA approaches, the book describes the advances that have been made in applying them to arthritis, lupus, multiple sclerosis, diabetes, Sjogren`s syndrome and transplantation.One chapter is devoted to discussing the first human clinical trials that apply gene therapy to the treatment of an inflammatory disease. As well as providing novel therapeutic approaches, gene therapy facilitates the development of new and improved animal models of disease; a chapter describing these advances is also included. As an up-to-date, timely book written by th
Combinatorial chemistry in conjunction with High Throughput Screening (HTS) is revolutionizing the drug discovery process.
The TGF-13 superfamily is a large and expanding multigene family which in verte brates includes the TGF-13 proteins themselves, the bone morphogenetic proteins (BMPs), the growth and differentiation factors (GDF), the activins/inhibins (INH), Mullerian inhibitory substance (MIS), glial derived neurotropic factor (GDNF) and more recently macrophage inhibitory cytokine 1 (MIC-1). They are characterised by conserved structural elements and a broad commonality of function. Major structural elements All members of the TGF-13 superfamily contain as their major structural hallmark a conserved spacing and distribution of seven cysteine residues. This structure is known as the cysteine knot and tethers together regions of the peptide as well as binding the two chains of the dimer to each other. High resolution structures are now available on proteins from three families within this group including glial derived neurotropic factor (GDNF), BMP-7 and several of the TGF-13s. Despite low similarity between some of these proteins (eg, TGF-13s and GDNF are only 13% identical) they share a strikingly similar three dimensional conformation (Fig. 1). These structural elements imbue the protein with some of its familial characteristics. These include its physico-chemical stability due to tight tethering of portions of the peptide chain via criss-crossing disulphide bonds. Much of its surfaces are coated with hydrophobic patches leading to a propensity to bind non-specifically to other proteins as well as to its self. This also causes a marked propensity for aggregation when the recombinant protein is present at high concentration.
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.
Heart failure research is a most active area of research in academic, industrial and government-sponsored research and receives intense clinical attention.
Several new developments in the field of neuroimmunology with focus on the brain-to-immune system communication have been the incentive for this PIR volume. It covers topics such as brain-immune interactions, the impact of stress on the immune response, pain and immunosuppression, the modulation of inflammation and pain by the sympathetic nervous system, consequences of nerve injury for the immune system, neuronal mechanisms of immune cell recruitment, and the modulation of the immune response by corticotropin-releasing hormone or adenosine. The authors are a unique group of scientists who are all interested in brain-to-immune interactions; however, each from a different perspective. The volume will serve both neurobiologists and immunologists to understand the influence of the central nervous system on peripheral inflammation. Many aspects of this book will also be stimulating for researchers in the pain field.
The inflammasome was first described in 2002 as a molecular complex activating proinflammatory caspases and therefore regulating the maturation and biological activities of cytokines such as IL-1 and IL-18.
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.
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.
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.
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.
Over the past ten years, a number of cytokines and growth factors have proven to be as effective therapeutics.
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