Since the appearance of photosynthesis on our planet, all living organisms have been facing a new abundant, extremely reactive element, oxygen. This element is used for the synthesis of highly energetic compounds, but can also generate molecules capable of damaging constituents of living structures, including proteins, nucleic acids and lipids. It is therefore no surprise that all biological organisms have evolved multiple and sophisticated ways to reduce the detrimental effects of oxygen. For cells and tissues of highly organized animals, particularly cells of the immune system, superoxidation products play an important role, via oxidative stress, in activation, inflammation and viral and bacterial infections. We must be grateful to Drs. C. Pasquier, C. Auclair, L. Packer and R. Olivier for having brought together many specialists in an international meeting held in Paris in March 1993, at the Ministry of Research. This book comprises an impressive amount of recent knowledge, a real mine for the reader in this fast developing field of research. Furthermore, we should not forget that this basic research may lead in the future to new therapeutic approaches to the most important pathologies of the latter part of this century, including AIDS.

Oxidative Stress and Biomaterials provides readers with the latest information on biomaterials and the oxidative stress that can pose an especially troubling challenge to their biocompatibility, especially given the fact that, at the cellular level, the tissue environment is a harsh landscape of precipitating proteins, infiltrating leukocytes, released oxidants, and fluctuations of pH which, even with the slightest shift in stasis, can induce a perpetual state of chronic inflammation. No material is 100% non-inflammatory, non-toxic, non-teratogenic, non-carcinogenic, non-thrombogenic, and non-immunogenic in all biological settings and situations. In this embattled terrain, the most we can hope for from the biomaterials we design is a type of "meso-compatibility, a material which can remain functional and benign for as long as required without succumbing to this cellular onslaught and inducing a local inflammatory reaction. - Explores the challenges of designing and using biomaterials in order to minimize oxidative stress, reducing patterns of chronic inflammation and cell death - Brings together the two fields of biomaterials and the biology of oxidative stress - Provides approaches for the design of biomaterials with improved biocompatibility

Glutathione (GSH) has been described for a long time just as a defensive reagent against the action of toxic xenobiotics (drugs, pollutants, carcinogens), both directly and as a cofactor for GSH transferases. As a prototype antioxidant, it has been involved in cell protection from the noxious effect of excess oxidant stress, both directly and as a cofactor of glutathione peroxidases. In addition, it has long been known that GSH is capable of forming disulfide bonds with cysteine residues of proteins, and the relevance of this mechanism ("S-glutathionylation") in regulation of protein function has been well documented in a number of research fields. Rather paradoxically, it has also been highlighted that GSH—and notably its catabolites, as originated by metabolism by gamma-glutamyltransferase—can promote oxidative processes, by participating in metal ion-mediated reactions eventually leading to formation of reactive oxygen species and free radicals. Also, a fundamental role of GSH has been recognized in the storage and transport of nitric oxide (NO), in the form of S-nitrosoglutathione (GSNO). The significance of GSH as a major factor in regulation of cell life, proliferation, and death, can be regarded as the integrated result of all these roles, as well as of more which are emerging in diverse fields of biology and pathophysiology. Against this background, modulation of GSH levels and GSH-related enzyme activities represents a fertile field for experimental pharmacology in numerous and diverse perspectives of animal, plant and microbiologic research. This research topic includes 14 articles, i.e. 4 Opinion Articles, 6 Reviews, and 4 Original Research Articles. The contributions by several distinguished research groups, each from his own standpoint of competence and expertise, provide a comprehensive and updated view over the diverse roles, the changing faces of GSH and GSH-related enzymes in cell’s health, disease and death.

One of the major biomedical triumphs of the post-World War II era was the defmitive demonstration that hypercholesterolemia is a key causative factor in atherosclerosis; that hypercholesterolemia can be effectively treated; and that treatment significantly reduces not only coronary disease mortality but also all cause mortality. Treatment to lower plasma levels of cholesterol - primarily low density lipoprotein (LDL) cholesterol - is now accepted as best medical practice and both physicians and patients are being educated to take aggressive measures to lower LDL. We can confidently look forward to important decreases in the toll of coronary artery disease over the coming decades. However, there is still uncertainty as to the exact mechanisms by which elevated plasma cholesterol and LDL levels initiate and favor the progression of lesions. There is general consensus that one of the earliest responses to hypercholesterolemia is the adhesion of monocytes to aortic endothelial cells followed by their penetration into the subendothelial space, where they differentiate into macrophages. These cells, and also medial smooth muscle cells that have migrated into the subendothelial space, then become loaded with mUltiple, large droplets of cholesterol esters . . . the hallmark of the earliest visible atherosclerotic lesion, the so-called fatty streak. This lesion is the precursor of the more advanced lesions, both in animal models and in humans. Thus the centrality of hypercholesterolemia cannot be overstated. Still, the atherogenic process is complex and evolves over a long period of time.

Due to that at present, the majority of diseases are associated with alterations in oxidative stress and inflammatory processes, and in that Nrf-2 is a modulator of these processes; knowing how this transcriptional factor functions and is regulated opens a therapeutic window to diverse diseases. Therefore, the efforts of various investigation groups are centered on finding activators and/or inhibitors of Nrf-2 to prevent or control diverse diseases, for example, cancer, where it would be important to regulate Nrf-2 in order for it to activate apoptosis pathways in cancerogenous cells, or in neurodegenerative diseases where cell death is predominant, it would be important for Nrf-2 to activate antiapoptotic pathways.

Persistent Viral Infections Edited by Rafi Ahmed Emory Vaccine Center, Atlanta, USA and Irvin S. Y. Chen UCLA School of Medicine, Los Angeles, USA During the past decade much of our attention has focused on diseases associated with viral persistence. Major breakthroughs in immunology, and the advent of molecular approaches to study pathogenesis have increased our understanding of the complex virus-host interactions that occur during viral persistence. Persistent Viral Infections focuses on: * The pathogenesis and immunology of chronic infections * Animal models that provide, or have the potential to provide, major insights This volume will be essential reading for virologists, immunologists, oncologists and neurologists.

This authoritative handbook covers all aspects of immunosenescence, with contributions from experts in the research and clinical areas. It examines methods and models for studying immunosenescence; genetics; mechanisms including receptors and signal transduction; clinical relevance in disease states including infections, autoimmunity, cancer, metabolic syndrome, neurodegenerative diseases, frailty and osteoporosis; and much more.