Cyclosporine A-induced oxidative stress in rat hepatocytes.

In man the immunosuppressive drug Cyclosporine A (CsA) has been used successfully in organ transplantation and in the treatment of autoimmune disorders. The drug, however, causes side effects which occur mainly in the kidney but also in the liver. The mechanisms leading to the hepatic side effects are not yet fully understood. Because reactive oxygen production is a common mechanism of drug toxicity, the goal of this study was to evaluate whether CsA induces oxidative stress in rat liver cells. In primary rat hepatocyte 20-h cultures, CsA caused a concentration-dependent increase of free reactive oxygen species, thiobarbituric acid reactive substances, loss of protein thiols and decrease of molar ratios of glutathione and glutathione disulfide in the range of 0 to 50 microM CsA. The weakening or enforcement of the cellular glutathione state by the glutathione synthesis inhibitor buthionine sulfoximine or the glutathione disulfide -reducing agent dithiothreitol either increased or inhibited the CsA cytotoxicity, as determined by lactate dehydrogenase release. CsA also decreased the level of endogenous antioxidant ascorbic acid and increased its oxidation product dehydroascorbic acid. Supplementation of the cell cultures with ascorbic acid significantly reduced the CsA toxicity. The antioxidant DL-alpha-tocopherol-polyethylene-glycol-1000-succinate partly decreased CsA-mediated reactive oxygen species formation, totally decreased thiobarbituric acid reactive substances formation, prevented the loss of protein-bound sulfhydryl groups and in addition totally inhibited the CsA cytotoxicity. The present data provide good evidence that oxidative stress is part of the mechanism by which CsA causes toxicity in rat liver cells.

[Sympathetic skin response in Parkinson syndrome]. / Sympathische Hautantwort beim Parkinson-Syndrom.

Several tests of cardiovascular and gastrointestinal function have been approved for the diagnosis of autonomic regulation dysfunction in Parkinson's disease. In the present study we compared the diagnostic value of the sympathetic skin response (SSR) with the established methods. Ninety percent of the 20 patients we examined (10 women, 10 men, 46 to 80 years) showed pathological results in the cardiovascular function test. Fifty-five percent had a prolonged colon transit, indicating a gastrointestinal dysfunction. We saw pathologically prolonged latencies of the SSR in 35% of the patients, 55% had borderline results. Three of the 20 patients had pathological results in all of the functions examined. Half of the patients had two pathological results, whereas 7 patients were pathological in only one of the three examinations. We were unable to establish any correlation between the SSR and other results, and we also found no relationship between prolonged SSR and the duration of the disease.

[Aneurysms of the hepatic artery]. / Aneurysmen der Arteria hepatica.

A series of seven cases of hepatic artery aneurysms is reported. Guidelines for diagnosis and therapeutic approach to this rare disease are specified based on our own results and on the work of other authors. Because of high mortality, hepatic and biliary complications in cases of ruptured hepatic aneurysms elective vascular surgery is recommended in symptomatic and asymptomatic patients. In cases of intrahepatic localization percutaneous catheter embolization may be the method of choice except for some cases of false aneurysms in transplanted livers.