Oxidative stress in the context of acute cerebrovascular stroke.

BACKGROUND AND PURPOSE: Free radical generation and consequent oxidative stress in thrombotic cerebrovascular stroke have a distinctive role in the pathogenesis of ischemic brain injury. One of the potential injurious effects of homocyst(e)ine in occlusive vascular diseases is free radical generation. In the current study, we investigated the status of oxidant stress in the acute phase of thrombotic cerebrovascular stroke and the possible role of homocyst(e)ine. METHODS: We determined levels of plasma homocyst(e)ine, lipid peroxide, ascorbic acid, superoxide dismutase, and nitric oxide in 30 patients with thrombotic cerebrovascular stroke within 2 days of the onset of the attack as well as in 22 healthy volunteers of comparable age and gender. RESULTS: Statistically significant elevation of homocyst(e)ine (P<0. 001), lipid peroxide (P<0.001), and nitric oxide (P<0.001) plasma levels were observed in stroke patients compared with healthy controls. On the other hand, the antioxidant ascorbic acid plasma levels were significantly lower in the patient group compared with healthy control subjects (P<0.001). Meanwhile, superoxide dismutase plasma levels were not statistically different in either groups. The study also revealed a significant and strong positive correlation between homocyst(e)ine and lipid peroxide (r=0.85, P<0.001). Ascorbic acid plasma levels were significantly negatively correlated with both homocyst(e)ine (r=-0.875, P<0.001) and lipid peroxide (r=-0.576, P<0.001). The nitric oxide level was positively correlated with superoxide dismutase (r=0.396, P<0.05). CONCLUSIONS: We conclude that hyperhomocyst(e)inemia is a possible causal factor in free radical generation during the acute phase of thrombotic cerebrovascular stroke. Pharmacological intervention could potentially be beneficial in this setting and warrants further evaluation.

Clinical and biochemical studies of bone destruction in cholesteatoma.

The exact causative factor(s) of bone erosion in cholesteatoma are not known. In recent years, the possible role of cytokines has drawn attention. Since the studies on cytokines in cholesteatoma are limited and depend on histopathological methods, the present work approached this subject by biochemical determination of TNF-alpha lysosomal enzymes, acid phosphatase (total and tartrate resistant), cathepsin B, leucyl aminopeptidase lysozyme together with non-lysosomal enzymes calpain I and II in 50 cholesteatoma samples (epithelial and subepithelial tissues) in comparison with 14 normal skin samples from the external ear canal. The study revealed significantly increased levels of all previous indices in cholesteatoma epithelium and subepithelial tissues compared with healthy skin. The levels of these indices reflected the clinical severity of the disease as reflected by their significant increase in cases with erosion of two or three ossicles, erosion of dural plate, sinus plate and facial canal and more extensive cholesteatoma. It is likely that TNF-alpha acts both directly by causing bone erosion and indirectly by stimulating the release of lysosomal enzymes. The latter mechanism is supported by the significant correlations observed between TNF-alpha and lysosomal enzymes. The non-lysosomal enzymes calpain I and II seem to participate in the bone erosion associated with cholesteatoma by their involvement in collagen destruction. Due to the suggested role of TNF-alpha in bone destruction associated with cholesteatoma the use of anti-inflammatory drugs should be taken into consideration in otitis media to diminish bone destruction. Similarly, antibiotics should be used to prevent the deleterious effects of bacterial endotoxin.