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Isabel Meister Katrin Ingram-Sieber Noemi Cowan Matthew Todd Murray N. Robertson Claudia Meli Malay Patra Gilles Gasser Jennifer Keiser 《Antimicrobial agents and chemotherapy》2014,58(9):5466-5472
A racemic mixture of R and S enantiomers of praziquantel (PZQ) is currently the treatment of choice for schistosomiasis. Though the S enantiomer and the metabolites are presumed to contribute only a little to the activity of the drug, in-depth side-by-side studies are lacking. The aim of this study was to investigate the in vitro activities of PZQ and its main metabolites, namely, R- and S-cis- and R- and S-trans-4′-hydroxypraziquantel, against adult worms and newly transformed schistosomula (NTS). Additionally, we explored the in vivo activity and hepatic shift (i.e., the migration of the worms to the liver) produced by each PZQ enantiomer in mice. Fifty percent inhibitory concentrations of R-PZQ, S-PZQ, and R-trans- and R-cis-4′-hydroxypraziquantel of 0.02, 5.85, 4.08, and 2.42 μg/ml, respectively, for adult S. mansoni were determined in vitro. S-trans- and S-cis-4′-hydroxypraziquantel were not active at 100 μg/ml. These results are consistent with microcalorimetry data and studies with NTS. In vivo, single 400-mg/kg oral doses of R-PZQ and S-PZQ achieved worm burden reductions of 100 and 19%, respectively. Moreover, worms treated in vivo with S-PZQ displayed an only transient hepatic shift and returned to the mesenteric veins within 24 h. Our data confirm that R-PZQ is the main effector molecule, while S-PZQ and the metabolites do not play a significant role in the antischistosomal properties of PZQ. 相似文献
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Stephen PH Alexander 《British journal of pharmacology》2012,167(8):1573-1574
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Marshall Hagins PT PhD Andrew Rundle PH Nathan S. Consedine PhD Sat Bir S. Khalsa PhD 《Journal of clinical hypertension (Greenwich, Conn.)》2014,16(1):54-62
The purpose of this study was to compare the effects of yoga with an active control (nonaerobic exercise) in individuals with prehypertension and stage 1 hypertension. A randomized clinical trial was performed using two arms: (1) yoga and (2) active control. Primary outcomes were 24‐hour day and night ambulatory systolic and diastolic blood pressures. Within‐group and between‐group analyses were performed using paired t tests and repeated‐measures analysis of variance (time × group), respectively. Eighty‐four participants enrolled, with 68 participants completing the trial. Within‐group analyses found 24‐hour diastolic, night diastolic, and mean arterial pressure all significantly reduced in the yoga group (?3.93, ?4.7, ?4.23 mm Hg, respectively) but no significant within‐group changes in the active control group. Direct comparisons of the yoga intervention with the control group found a single blood pressure variable (diastolic night) to be significantly different (P=.038). This study has demonstrated that a yoga intervention can lower blood pressure in patients with mild hypertension. Although this study was not adequately powered to show between‐group differences, the size of the yoga‐induced blood pressure reduction appears to justify performing a definitive trial of this intervention to test whether it can provide meaningful therapeutic value for the management of hypertension. 相似文献
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