Bioactive extracts of Citrus aurantifolia swingle seeds obtained by supercritical CO<inf>2</inf> and organic solvents comparing its cytotoxic activity against L5178Y leukemia lymphoblasts

Citrus seeds are sources of secondary metabolites including limonoids, which have demonstrated cytotoxic activity. There are several reports of limonoid extraction methods. However, there are no studies that compare extraction methods and their optimization. The aim of this work was to evaluate two extraction methods for obtaining limonoid extracts from Citrus aurantifolia seeds and to evaluate their cytotoxic activity against L5178Y lymphoma cells. In solvent extraction, we evaluated two factors: time and solvent type, while for supercritical extraction, pressure and temperature were evaluated. Cytotoxic activities of extracts were carried out in vitro. Time and solvent did not affect cytotoxic activity, but they did affect limonin content and yield extraction. Supercritical extraction pressure did not affect the limonin yield, but latter was affected by temperature process. There was no difference in cytotoxic activity between extracts, showing an IC50 of 8.5 ?g/mL for supercritical CO2 and of 9 ?g/mL for solvent extracts. Zapotitlán 2015, Elsevier B.V. All rights reserved

Vorapaxar in the secondary prevention of atherothrombotic events

Item does not contain fulltextBACKGROUND: Thrombin potently activates platelets through the protease-activated receptor PAR-1. Vorapaxar is a novel antiplatelet agent that selectively inhibits the cellular actions of thrombin through antagonism of PAR-1. METHODS: We randomly assigned 26,449 patients who had a history of myocardial infarction, ischemic stroke, or peripheral arterial disease to receive vorapaxar (2.5 mg daily) or matching placebo and followed them for a median of 30 months. The primary efficacy end point was the composite of death from cardiovascular causes, myocardial infarction, or stroke. After 2 years, the data and safety monitoring board recommended discontinuation of the study treatment in patients with a history of stroke owing to the risk of intracranial hemorrhage. RESULTS: At 3 years, the primary end point had occurred in 1028 patients (9.3%) in the vorapaxar group and in 1176 patients (10.5%) in the placebo group (hazard ratio for the vorapaxar group, 0.87; 95% confidence interval [CI], 0.80 to 0.94; P<0.001). Cardiovascular death, myocardial infarction, stroke, or recurrent ischemia leading to revascularization occurred in 1259 patients (11.2%) in the vorapaxar group and 1417 patients (12.4%) in the placebo group (hazard ratio, 0.88; 95% CI, 0.82 to 0.95; P=0.001). Moderate or severe bleeding occurred in 4.2% of patients who received vorapaxar and 2.5% of those who received placebo (hazard ratio, 1.66; 95% CI, 1.43 to 1.93; P<0.001). There was an increase in the rate of intracranial hemorrhage in the vorapaxar group (1.0%, vs. 0.5% in the placebo group; P<0.001). CONCLUSIONS: Inhibition of PAR-1 with vorapaxar reduced the risk of cardiovascular death or ischemic events in patients with stable atherosclerosis who were receiving standard therapy. However, it increased the risk of moderate or severe bleeding, including intracranial hemorrhage. (Funded by Merck; TRA 2P-TIMI 50 ClinicalTrials.gov number, NCT00526474.)