Pathophysiological role specificity

More recent studies also suggest that increased IL-6 production is associated with age-related depression (D6) and disability due to muscle atrophy and/or various specific diseases (F8). Moreover, Straub et al. (S30) suggest that increased IL-6 levels may be secondary to diminished levels of the steroid hormone, dehy-droepiandrosterone (see below under neuroendocrine aging theory). The pathophysiologic role of IL-6 in human disease has been recently reviewed (P7). 

A highly specific neutralizing antibody to IL-8 was administered intravenously at the initiation of reperfusion in order to evaluate the pathophysiological role of IL-8 in brain reperfusion injury. Neutrophil aggregation to the endothelium and infiltration into parenchyma were significantly inhibited in brain reperfused for 6 h. 

B cells also have impact on T-cell differentiation. B-cell antigen presentation plays an important role at promoting Th2 responses and pathophysiology during allergic disorders. It has been shown that B-cell -/- mice and in mice selectively deficient in MHCII on B cells had decreased Th2 cytokines IL-4 and IL-5 [152]. Also in another study it has been reported that B-cell-derived exosomes can present allergen peptides and activate allergen-specific T cells to proliferate and produce Th2 cytokines IL-5 and IL-13 [42]. 

The expression of 15-LOX in atherosclerotic lesions is one of the major causes of LDL oxidative modification during atherosclerosis. To obtain the experimental evidence of a principal role of 15-LOX in atherosclerosis under in vivo conditions, Kuhn et al. [67] studied the structure of oxidized LDL isolated from the aorta of rabbits fed with a cholesterol-rich diet. It was found that specific LOX products were present in early atherosclerotic lesions. On the later stages of atherosclerosis the content of these products diminished while the amount of products originating from nonenzymatic lipid peroxidation increased. It was concluded that arachidonate 15-LOX is of pathophysiological importance at the early stages of atherosclerosis. Folcik et al. [68] demonstrated that 15-LOX contributed to the oxidation of LDL in human atherosclerotic plaques because they observed an increase in the stereospecificity of oxidation in oxidized products. Arachidonate 15-LOX is apparently more active in young human lesions and therefore, may be of pathophysiological importance for earlier atherosclerosis. In advanced human plaques nonenzymatic lipid peroxidation products prevailed [69],... 

Patients with both type 1 and type 2 diabetes are prone to complications. The specific chronic diabetic complications are due to microangiopathy and include neuropathy, retinopathy and nephropathy. Recent data stress the vital role of hyperglycaemia and oxidative stress in their pathophysiology. Premature atherosclerosis (which can be considered... 

There is also evidence of low levels of 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid (CSF) of impulsive individuals. We might hypothesize that, in a nonresponsive, impulsive patient, diminished serotonin plays a role in the pathophysiology. This hypothesis could now be tested and simultaneously serve as the foundation for a pathophysiologically based treatment by choosing therapies specific for various components of this system. For example, the 5-HT agonist buspirone might be tried, because there is limited evidence from open trials that it has antiaggressive properties. 

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