Purpose St John's wort (Hypericum perforatum) is an herbal remedy that is widely used in the treatment of depression. Recent clinical data have demonstrated that St John's wort extracts interfere with the action of various drugs and possibly also with combined oral contraceptives. Therefore, we investigated the effects of a St John's wort extract (Ze 117) with low hyperforin content on the pharmacokinetics of ethinylestradiol and 3-ketodesogestrel. Method Sixteen healthy female volunteers, who had taken a low-dose oral contraceptive (Lovelle contains 0.02 mg ethinylestradiol + 0.15 mg desogestrel) for at least 3 months, participated in the study. Pharmacokinetic data (AUC, C max , t max ) were determined the day before (reference) and after (test) a 14-day period of Ze 117 intake (250 mg twice daily).Results Before the co-administration of Ze 117 on day 7, the geometric mean (geometric coefficient of variation) for the AUC 0-24 of ethinylestradiol was 152.53 pg·h/ml (87.39%) and after co-administration on day 21 it was 196.57 pg·h/ml (78.14%). The respective values for ketodesogestrel were 36.37 pg·h/ml (34.18%) and 41.12 pg·h/ml (34.36%). The mean of individual ratios (reference-to-test) of log-transformed AUC values (90% confidence interval) were 0.951 (0.915-0.986) for ethinylestradiol and 0.968 (0.944-0.992) for ketodesogestrel indicating a small loss in bioavilability, but bioequivalence nevertheless. Conclusion These results indicate that the recommended dose of the hypericum extract Ze117, which has a low hyperforin content, does not interact with the pharmacokinetics of the hormonal components of the low-dose oral contraceptive.

Phosphorylation of phospholamban and development of reticular Ca2+ transport were studied in crude membrane preparations of embryonic, newborn and adult chick heart. Maximal phosphorylation of phospholamban by added catalytic subunit of cyclic AMP-dependent protein kinase increases from embryonic day 4-15. It decreases with further development. In the same membrane preparations active Ca2+-uptake into vesicles of sarcoplasmic reticulum rises from day 4-7 and decreases then slightly until day 20. A several-fold increase in Ca2+ -transport activity occurs at the time of hatching. The data indicate separate genetic control for synthesis of phospholamban and sarcoplasmic reticulum Ca'+-ATPase. Cardiac muscle Ontogenesis Sarcoplasmic reticutum &+-transport Phospholamban

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The irreversible loss of activity of the sarcolemma-localized beta-receptor-adenylyl cyclase system (beta-RAS) in myocardial ischemia is a well documented phenomenon. Alterations in the sarcolemma (SL) induced by reactive O2 species could be responsible for this loss. Therefore the influence of oxidation of SH-groups and lipid peroxidation induced by Fe2+/Vit. C on the beta-RAS activity was studied. During incubation of SL with Fe2+/Vit. C a transient enhancement followed by a continuous loss of the beta-RAS activity (isoprenaline-, NaF-, Gpp(NH)p-, forskolin-stimulated and basal activity) was observed. In contrast there occurred a continuous loss of SH-groups and lipid peroxidation, beginning immediately after the start of incubation. Loss of SH-groups and lipid peroxidation as well as changes in the beta-RAS did not take place in the presence of the antioxidant t-Butyl-4-hydroxyanisole (BHA) or the Fe(2+)-chelator EGTA. In view of the known ischemia-induced formation of reactive O2 species our results show that these powerful oxidants could contribute to the modulation of the beta-RAS during myocardial ischemia.

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