Effect of gender difference on platelet reactivity

Background Previous studies have suggested that women do not accrue equal therapeutic benefit from antiplatelet medication as compared with men. The physiological mechanism and clinical implications behind this gender disparity have yet to be established. Methods On-treatment platelet reactivity was determined in 717 men and 234 women on dual antiplatelet therapy, undergoing elective coronary stent implantation. Platelet function testing was performed using arachidonic acid and adenosine diphosphate-induced light transmittance aggregometry (LTA) and the VerifyNow P2Y12 and Aspirin assays. Also the incidence of all-cause death, non-fatal acute myocardial infarction, stent thrombosis and ischaemic stroke was evaluated. Results Women had higher baseline platelet counts than men. Women exhibited a higher magnitude of on-aspirin platelet reactivity using LTA, but not using the VerifyNow Aspirin assay. The magnitude of on-clopidogrel platelet reactivity was significantly higher in women as compared with men with both tests used. The cut-off value to identify patients at risk as well as the incidence of clinical endpoints was similar between women and men (16/234[6.8%] vs. 62/717[8.6%], p=0.38). Conclusion Although the magnitude of platelet reactivity was higher in women, the absolute difference between genders was small and both the cut-off value to identify patients at risk and the incidence of the composite endpoint were similar between genders. Thus, it is unlikely that the difference in platelet reactivity accounts for a worse prognosis in women

HDAC Inhibition Decreases the Expression of EGFR in Colorectal Cancer Cells

Epidermal growth factor receptor (EGFR), a receptor tyrosine kinase which promotes cell proliferation and survival, is abnormally overexpressed in numerous tumors of epithelial origin, including colorectal cancer (CRC). EGFR monoclonal antibodies have been shown to increase the median survival and are approved for the treatment of colorectal cancer. Histone deacetylases (HDACs), frequently overexpressed in colorectal cancer and several malignancies, are another attractive targets for cancer therapy. Several inhibitors of HDACs (HDACi) are developed and exhibit powerful antitumor abilities. In this study, human colorectal cancer cells treated with HDACi exhibited reduced EGFR expression, thereby disturbed EGF-induced ERK and Akt phosphorylation. HDACi also decreased the expression of SGLT1, an active glucose transporter found to be stabilized by EGFR, and suppressed the glucose uptake of cancer cells. HDACi suppressed the transcription of EGFR and class I HDACs were proved to be involved in this event. Chromatin immunoprecipitation analysis showed that HDACi caused the dissociation of SP1, HDAC3 and CBP from EGFR promoter. Our data suggested that HDACi could serve as a single agent to block both EGFR and HDAC, and may bring more benefits to the development of CRC therapy

The Psychological effect of electoral systems in founding elections

In this research note, I revisit the conventional wisdom about when the psychological effect of electoral systems is observed. I rely on data from the first presidential and legislative elections in 45 third- and fourth-wave presidential and semi-presidential regimes to show that the psychological effect of electoral systems manifests itself in the first election. The effective number of legislative parties is significantly higher than the effective number of presidential candidates in the first election when the electoral system in legislative elections is more permissive than in presidential elections.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Ministerio de Economía y Competitividad of Spain under the research project CSO2013-40723-C2-1-R