Endothelial Effect of Statin Therapy at a High Dose Versus Low Dose Associated with Ezetimibe

Abstract Background: The effect of statins on the endothelial function in humans remains under discussion. Particularly, it is still unclear if the improvement in endothelial function is due to a reduction in LDL-cholesterol or to an arterial pleiotropic effect. Objective: To test the hypothesis that modulation of the endothelial function promoted by statins is primarily mediated by the degree of reduction in LDL-cholesterol, independent of the dose of statin administered. Methods: Randomized clinical trial with two groups of lipid-lowering treatment (16 patients/each) and one placebo group (14 patients). The two active groups were designed to promote a similar degree of reduction in LDL-cholesterol: the first used statin at a high dose (80 mg, simvastatin 80 group) and the second used statin at a low dose (10 mg) associated with ezetimibe (10 mg, simvastatin 10/ezetimibe group) to optimize the hypolipidemic effect. The endothelial function was assessed by flow-mediated vasodilation (FMV) before and 8 weeks after treatment. Results: The decrease in LDL-cholesterol was similar between the groups simvastatin 80 and simvastatin 10/ezetimibe (27% ± 31% and 30% ± 29%, respectively, p = 0.75). The simvastatin 80 group presented an increase in FMV from 8.4% ± 4.3% at baseline to 11% ± 4.2% after 8 weeks (p = 0.02). Similarly, the group simvastatin 10/ezetimibe showed improvement in FMV from 7.3% ± 3.9% to 12% ± 4.4% (p = 0.001). The placebo group showed no variation in LDL-cholesterol level or endothelial function. Conclusion: The improvement in endothelial function with statin seems to depend more on a reduction in LDL-cholesterol levels, independent of the dose of statin administered, than on pleiotropic mechanisms.

Colchicine to Reduce Atrial Fibrillation in the Postoperative Period of Myocardial Revascularization

Abstract Background: The high prevalence of atrial fibrillation (AF) in the postoperative period of myocardial revascularization surgery increases morbidity and mortality. Objective: To assess the efficacy of colchicine to prevent AF in the postoperative period of myocardial revascularization surgery, the impact of AF on hospital length of stay and death, and to identify its risk factors. Methods: Between May 2012 and November 2013, 140 patients submitted to myocardial revascularization surgery were randomized, 69 to the control group and 71 to the colchicine group. Colchicine was used at the dose of 1 mg orally, twice daily, preoperatively, and of 0.5 mg, twice daily, until hospital discharge. A single dose of 1 mg was administered to those admitted 12 hours or less before surgery. Results: The primary endpoint was AF rate in the postoperative period of myocardial revascularization surgery. Colchicine group patients showed no reduction in AF incidence as compared to control group patients (7.04% versus 13.04%, respectively; p = 0.271). There was no statistically significant difference between the groups regarding death from any cause rate (5.6% versus 10.1%; p = 0,363) and hospital length of stay (14.5 ± 11.5 versus 13.3 ± 9.4 days; p = 0.490). However, colchicine group patients had a higher infection rate (26.8% versus 8.7%; p = 0.007). Conclusion: The use of colchicine to prevent AF after myocardial revascularization surgery was not effective in the present study. Brazilian Registry of Clinical Trials number RBR-556dhr.

Brazilian flora extracts as source of novel antileishmanial and antifungal compounds

Natural products have long been providing important drug leads for infectious diseases. Leishmaniasis is a protozoan parasitic disease found mainly in developing countries, and it has toxic therapies with few alternatives. Fungal infections have been the main cause of death in immunocompromised patients and new drugs are urgently needed. In this work, a total of 16 plant species belonging to 11 families, selected on an ethnopharmacological basis, were analyzed in vitro against Leishmania (L.) chagasi, Leishmania (L.) amazonensis, Candida krusei, and C. parapsilosis. Of these plant species, seven showed antifungal activity against C. krusei, five showed antileishmanial activity against L. chagasi and four against L. amazonensis, among them species of genus Plectranthus. Our findings confirm the traditional therapeutic use of these plants in the treatment of infectious and inflammatory disorders and also offer insights into the isolation of active and novel drug prototypes, especially those used against neglected diseases as Leishmaniasis.