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In rat thymocytes and cerebellar granule cells, reactive oxygen species (ROS) levels were increased and cell viability was decreased as a result of exposure to ethanol (up to 0.4%). Thymocytes showed larger increases in ROS levels, but neurons showed more pronounced decreases in cell viability. These parameters in neurons were relatively unaffected when the cells were incubated with ethanol in the presence of inhibitors of alcohol-oxidizing enzymes, but in thymocytes, the presence of diallyl sulfide (an inhibitor of alcohol-inducible cytochrome P450, CYP2E1) or 4-methylpyrazole (an inhibitor of CYP2E1 and alcohol dehydrogenase) caused decreases in ROS production from ethanol. In both cell types, the presence of 3-aminotriazole (an inhibitor of catalase) did not decrease ROS production from ethanol. These studies show that the cytotoxic effects of ethanol in neurons may not be the result of oxidative metabolism of ethanol, whereas in thymocytes, the cytotoxic effect of ethanol is principally a result of its oxidative metabolism.

The effects of captopril and hydralazine, two commonly used antihypertensive drugs, on free radical generation and the onset of apoptosis in neuron and thymocyte preparations from 10-12 day old rats have been studied. Apoptosis was induced in neurons by kainate or N-methyl-D-aspartate and in thymocytes by heat shock. Intracellular free radical production was measured by 2',7'-dichlorofluorescein fluorescence, and apoptotic cells were detected by cell staining with fluorescein-labelled annexin V. Captopril was found to have no effect on intracellular free radical generation and also had no significant effect on the early stages of apoptosis in neurons and thymocytes. In contrast, hydralazine was found to decrease free radical generation in both neurons and thymocytes, and it also significantly decreased the numbers of apoptotic cells when neurons and thymocytes were stimulated for apoptosis. Hydralazine had a greater effect on decreasing free radical generation in neurons than in thymocytes, but it had a more pronounced effect on decreasing apoptosis in thymocytes compared to neurons, suggesting that apoptosis, under our experimental conditions, may not solely be triggered by free radical generation. These results contrast with earlier reports that captopril is a free radical scavenger and can decrease apoptosis in T-lymphocytes and cardiomyocytes, and the results obtained with hydralazine are in apparent disagreement with earlier reports that this drug is a free radical generator and can cause intracellular damage suggestive of enhanced free radical formation.

Background Ephedra is a sympathomimetic commonly used for the purposes of athletic performance enhancement and weight loss. It is known to be associated with gastrointestinal and psychiatric manifestations. We report here on 6 cases of dilated cardiomyopathy associated with ephedra use. Methods and results Over a period of 18 months, 6 patients attending our outpatient department with new onset heart failure were noted to have exposure to ephedra. The case record was reviewed and detailed clinical and echocardiographic data were extracted. All 6 patients (4 males) had left ventricular dysfunction at presentation (mean ejection fraction 20 ± 5%) and were treated with conventional heart failure pharmacotherapy. All patients discontinued ephedra use as advised. New York Heart Association class improved from class III in 5 patients (class II in 1 patient) to class I, within a median of 6 months (range 3–96). Ejection fraction improved to a mean of 47 ± 6%. Conclusions Ephedra may be associated with left ventricular systolic dysfunction. Withdrawal of this agent, in conjunction with proven pharmacotherapy, results in a significant improvement in functional status and left ventricular ejection fraction. We recommend specific enquiry into the use of over-the-counter supplements, particularly ephedra and its derivatives, when being evaluated with heart failure symptoms. These cases illustrate the potential risk of ephedra and provide additional support for the recent decision to ban this supplement.

A 56-year-old woman with a history of surgical removal of a invasive myocardial lipoma presented with progressive dyspnea. Transthoracic echocardiogram showed severe mitral and tricuspid regurgitation and severely impaired biventricular systolic function. Cardiac computed tomography was performed, showing extensive biventricular basal and mid-myocardial replacement by an infiltrating tumor that had the density of fat resulting in large aneurysms of the basal segments of both the ventricles. The patient is currently awaiting orthotopic heart transplantation.