Annals of Clinical and Laboratory Science 

About: Annals of Clinical and Laboratory Science is an academic journal published by Association of Clinical Scientists. The journal publishes majorly in the area(s): Medicine & Population. It has an ISSN identifier of 0091-7370. Over the lifetime, 3242 publications have been published receiving 45380 citations. The journal is also known as: Annals of clinical & laboratory science & Annals of clinical laboratory science.

Review : Free radicals, antioxidants, and the immune system

Abstract: Oxygen-derived free radicals are important in both natural and acquired immunity. Neutrophil and macrophage phagocytosis stimulates various cellular processes including the "respiratory burst" whereby increased cellular oxygen uptake results in the production of the potent oxidant bactericidal agents, hypochlorous acid and hydroxyl radical. In addition, nitric oxide, a gaseous radical produced by macrophages, reacts with superoxide to form peroxynitrite, also a potent bactericidal agent. Conversely, oxidative stress may be detrimental in acquired immunity by activation of nuclear factor kappa B, which governs gene expression involving various cytokines, chemokines, and cell adhesion molecules, among others. However, antioxidant supplementation essentially reverses several age-associated immune deficiencies, resulting in increased levels of interleukin-2, elevated numbers of total lymphocytes and T-cell subsets, enhanced mitogen responsiveness, increased killer cell activity, augmented antibody response to antigen stimulation, decreased lipid peroxidation, and decreased prostaglandin synthesis.

Molecular pathology of cyclooxygenase-2 in neoplasia

Abstract: Cyclooxygenase (COX)-2 levels are elevated in several types of human cancer tissues. Nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit both the COX-1 and COX-2 protein, the two enzymes that convert arachidonic acids to prostaglandins. Regular use of such NSAIDs significantly reduces the risk and spread of some cancers. The objective of this study was to elucidate the molecular pathology of neoplasms that overexpress COX-2. Epidemiological data and clinical studies were analyzed and compared with results of studies of human tumor tissues, animal models, and cultured tumor cells. COX-2, but not COX-1, is highly expressed in human colon carcinoma, squamous cell carcinoma of the esophagus, and skin cancer. COX-2 is inducible by oncogenes ras and scr, interleukin-1, hypoxia, benzo[a]pyrene, ultraviolet light, epidermal growth factor, transforming growth factor beta, and tumor necrosis factor alpha. Dexamethasone, antioxidants, and tumor-suppressor protein p53 suppress COX-2 expression. COX-2 synthesizes prostaglandin E2 (PGE2) which stimulates bcl-2 and inhibits apoptosis, and induces interleukin-6 (IL-6) which enhances haptoglobin synthesis. PGE2 is associated with tumor metastases, IL-6 with cancer cell invasion, and haptoglobin with implantation and angiogenesis. Drastic reduction in polyp number results from COX-2 gene knockout as well as from selective COX-2 inhibition in a mouse model of human familial adenomatous polyposis. Nonselective NSAIDs, for instance aspirin, and selective COX-2 inhibitors such as celecoxib (SC-58635) and NS-398 suppress azoxymethane-induced colon carcinogenesis in rats. Aspirin, indomethacin, and ibuprofen decrease cultured lung cancer cell proliferation. Selective inhibition of COX-2 is preferable to nonselective inhibition. It reduces cancer cell proliferation, induces cancer cell apoptosis, and spares COX-1-induced cytoprotection of the gastrointestinal tract.

Effects of iron overload on the immune system

Abstract: Iron and its binding proteins have immunoregulatory properties, and shifting of immunoregulatory balances by iron excess or deficiency may produce severe, deleterious physiological effects. Effects of iron overload include decreased antibody-mediated and mitogen-stimulated phagocytosis by monocytes and macrophages, alterations in T-lymphocyte subsets, and modification of lymphocyte distribution in different compartments of the immune system. The importance of iron in regulating the expression of T-lymphocyte cell surface markers, influencing the expansion of different T-cell subsets, and affecting immune cell functions can be demonstrated in vitro and in vivo. The poor ability of lymphocytes to sequester excess iron in ferritin may help to explain the immune system abnormalities in iron-overloaded patients. Iron overload as seen in hereditary hemochromatosis patients enhances suppressor T-cell (CD8) numbers and activity, decreases the proliferative capacity, numbers, and activity of helper T cells (CD4) with increases in CD8/CD4 ratios, impairs the generation of cytotoxic T cells, and alters immunoglobulin secretion when compared to treated hereditary hemochromatosis patients or controls. A correlation has recently been found between low CD8+ lymphocyte numbers, liver damage associated with HCV positivity, and severity of iron overload in beta-thalassemia major patients. Iron overload, with its associated increases of serum iron levels and transferrin saturation, may cause a poor response to interferon therapy. Iron overload with hyperferremia is associated with suppressed functions of the complement system (classic or alternative types). High plasma ferritin content in patients with chronic, diffuse diseases of the liver (cirrhosis, chronic hepatitis), beta-thalassemia major, dyserythropoiesis, and hereditary hemochromatosis may induce the development of anti-ferritin antibodies with the production of circulating immune complexes. Increased body stores of iron in various clinical situations may tip the immunoregulatory balance unfavorably to allow increased growth rates of cancer cells and infectious organisms, and complicate the clinical management of preexisting acute and chronic diseases.

Free radicals: their history and current status in aging and disease

Abstract: Oxygen toxicity was first described in laboratory animals in 1878 and was further established in 1899. The first experiment regarding a free radical reaction was reported in 1894. However, it was not until the late 1940s to early 1950s that retrolental fibroplasia in premature newborns was recognized as being due to oxygen toxicity and not until the late 1960s to early 1970s that newborn bronchopulmonary dysplasia and adult respiratory distress syndrome were appreciated by the medical community. Moreover, the presence of free radicals in biological systems was not generally considered likely until the discovery of superoxide dismutase in 1969, although in the 1950s the basis of oxygen toxicity and X-irradiation was proposed to be by a common free radical mechanism and the radical theory of aging was hypothesized. Oxyradicals are now widely accepted as being very important, not only in the aging process but also in numerous human diseases/disorders where they have either a primary or secondary role. Currently, there are extensive global basic research efforts to define more clearly the role of free radicals and oxidative stress in these conditions. Continuing clinical research will lead to more reliable treatment and preventive measures for many of them. In this review, a short history is presented and the current status of free radicals and oxidative stress in aging and various diseases is discussed.