One-hundred sixty patients (81 cyanidanol, 79 placebo) were included in a double-blind placebo-controlled clinical trial to evaluate the effect of 3 gm (+)-cyanidanol-3 per day for 8 weeks on the clinical course of acute viral hepatitis and HBsAg elimination. Quantitative determination of HBsAg was performed at frequent intervals. The mean time for serum bilirubin to decrease to 1.3 mg per dl was 30.8 +/- 3.5 days in the treated group and 52.2 +/- 9.8 days in the control group, (p less than 0.025). The time for SGOT to decrease to 100 IU per liter was 17.98 +/- 1.82 in the treated group and 26.53 +/- 3.7 in the control group (p less than 0.025). No significant difference in the evolution of other laboratory values or symptoms was found. The elimination rate of HBsAg was identical in both groups. Treatment did not alter the incidence of chronicity.

Acute Disease↗

PubMedDate not supplied

Hepatic zinc content in patients with various stages of alcoholic liver disease and in patients with chronic active and chronic persistent hepatitis.

The hepatic zinc content was determined in liver biopsies of patients with alcoholic and nonalcoholic liver disease using proton-induced X-ray emission. The values obtained in postmortem specimens of the liver from 27 patients with no evidence of acute or chronic liver disease served as controls. The mean value and the range of the zinc content in the controls (75 +/- 24 ppm wet weight) are in good agreement with those reported in the literature. The hepatic zinc content in the control group showed no significant age or sex dependence. The mean zinc content was significantly decreased in all groups of patients with alcoholic liver disease. The decrease was comparable in biopsies from patients with alcoholic fatty liver (-56.7%, n = 12), mild alcoholic hepatitis (-50.5%, n = 6) and alcoholic cirrhosis (-45.6%, n = 10). The hepatic zinc content was also distinctly reduced in patients with chronic active hepatitis (-60.3%, n = 15) and in those with chronic persistent hepatitis (-44.9%, n = 8). The estimation of the zinc content in subcellular fractions of the liver performed in postmortem specimens from seven patients with alcoholic liver cirrhosis and in six controls revealed a significant reduction in the zinc content in the fraction containing cell nuclei and membranes and in the mitochondrial fraction. A similar decrease was seen in the 100,000 g supernatant; however, the difference did not attain statistical difference. The zinc content of the microsomal fraction in the controls was lower than in the other three cell fractions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMedDate not supplied

The role of apoptosis in myocardial ischemia: a critical appraisal.

The role of apoptosis in cardiac ischemia is not clarified yet. Own data show that suicidal cell death is apparently not important in global ischemia where it only affects a small number of myocytes (8 %) while the majority of cells, i.e. 92 % die by oncosis. In acute regional ischemia it is most probably not a decisive factor. However, more solid data are needed to justify this statement. Human hibernating myocardium shows an activation of the apoptotic cascade, i.e., apoptosis might contribute to cell loss in this pathophysiological situation of multiple ischemic episodes. Manifold unresolved issues contribute to problems in determining the role of apoptosis in ischemia. These include 1) Uncertainty of the duration of the apoptotic cascade from activation of death receptors at the cellular membrane until DNA fragmentation occurs, 2) The role of the mitochondrial pathway, 3) The mode of removal of myocytes after cell death has occurred, 4) Technical problems such as specificity of the TUNEL method, detection of low abundance proteins such as activated caspases or cytochrome C, statistical considerations. These issues and many others should be clarified before any definite conclusion as to the role of apoptosis in ischemia may be drawn.

Animals↗

PubMedDate not supplied

The promise of new genetically engineered plasminogen activators.

The therapeutic efficacy of thrombolytic therapy for the treatment of acute myocardial infarction was first demonstrated convincingly in 1985 by the GISSI investigators. In the ensuing 10 years, continued clinical investigation has focused on improving the safety and efficacy of thrombolytic therapy. In addition to the use of adjunctive agents such as inhibitors of platelet aggregation and thrombin, new genetically engineered "second-generation" thrombolytic agents have been developed that offer the promise of improved clinical outcomes. The availability of these potent agents for clinical investigation offers the opportunity to determine the importance of properties such as fibrin specificity, plasma half-life, and resistance to inhibition. This review focuses on theoretical and practical aspects of optimizing thrombolytic therapy, survey of new agents on the clinical horizon, and the potential application of these agents for the treatment of patients with thrombotic occulusion of either coronary or peripheral arteries.

Arterial Occlusive Diseases↗

PubMedDate not supplied

Induction of endothelin-1 expression by oxidative stress in vascular smooth muscle cells.

Atherosclerosis is based on endothelial dysfunction leading to impaired vasomotor function. This is partially due to nitric oxide (NO) depletion caused by oxidative stress. Since the vasoconstrictor endothelin-1 (ET-1) might also be involved in endothelial dysfunction, we investigated whether oxidative stress regulates ET-1 expression in vascular smooth muscle cells (VSMC). Human aortic VSMC were treated with H(2)O(2) (200 microM) for up to 8 h. mRNA expression of preproendothelin (prepro-ET) was analyzed by RT-PCR. ET-1 protein and the marker for oxidative stress, 8-isoprostane, were determined by ELISA. Activity of cytosolic phospholipase A2 (cPLA(2)) as an indicator of ET-1 autocrine activity was measured photometrically. Stimulation of VSMC with H(2)O(2) resulted in increased expression of prepro-ET mRNA after 1 h with a maximum after 6 h (fourfold), similar to treatment with angiotensin II. ET-1 protein was significantly increased by H(2)O(2) treatment with a maximum after 8 h (P<.05). This effect was inhibited by the antioxidants resveratrol (100 microM) and quercetin (50 microM). In quiesced VSMC, incubation with H(2)O(2)-conditioned medium resulted in increased cPLA(2) activity compared to the controls (P<.05). This activity was partially inhibited by the ET(A)-receptor antagonist, PD 142893 (10 microM), indicating functional ET-1 in the conditioned medium. The presence of oxidative stress in H(2)O(2)-treated VSMC was associated by significantly increased formation of 8-isoprostane (P<.05). The data indicate for the first time that oxidative stress increases ET-1 generation and autocrine ET-1 activity in VSMC, a mechanism that might contribute to endothelial dysfunction in atherosclerosis.

Antioxidants↗