The best hope of controlling this pandemic is the development of a successful prophylactic vaccine. However, to date, this goal has proven to be exceptionally elusive. The recent failure of an experimental vaccine in a phase IIb study, named the STEP trial, intended solely to elicit cell-mediated immune responses against HIV-1, has highlighted the need for a balanced immune response consisting of not only cellular immunity but also a broad and potent humoral antibody response that can prevent infection with HIV-1. This article reviews the efforts made up to this point to elicit such antibody

responses, especially with regard to the use of a DNA prime-protein boost regimen, which has been proven to be a highly effective platform for GSK1210151A the induction of neutralizing antibodies in both animal and early-phase human studies.”
“Introduction: The vast majority of studies employing the isolated perfused rat heart model to study ischemic arrhythmias have used male rats only. The objective of this study was to determine the susceptibility to ischemia-induced ventricular fibrillation

(VF) in isolated female rat hearts in each stage of the estrous cycle that corresponds with a different endogenous reproductive hormonal environment. Methods: Hearts were isolated from female rats under pentobarbital anesthesia and perfused with modified Krebs solution containing BVD-523 3 mM K+. Experiments were grouped according to estrous cycle stage that was determined by prior vaginal lavage (n = 10-13 per group). A group of male rat hearts was used as the control. Regional ischemia was induced by coronary ligation and maintained for 30 min. The incidence of VF was determined from the ECG. Results: The incidence of VF in male hearts was 100%, while the incidence of VF in female hearts was also high but varied moderately with stage of the estrous cycle (diestrus 70%, metestrus 100%, proestrus 90%, estrus 69%; P > 0.05). Compared to male hearts, the onset of VF was similar in all groups except for hearts excised from rats in proestrus, in which it was delayed. There was no difference between groups in an arrhythmia

score, ischemic zone size, or baseline electrocardiographic or hemodynamic variables. Discussion: In conclusion, the susceptibility of isolated female rat hearts to ischemic VF is comparable to Bromosporine order that of male rat hearts, meaning that isolated female rat hearts can be used as controls in studies to assess antiarrhythmic drug efficacy. Since female rats can be used for isolated heart studies of ischemic VF, the need to cull female rats is reduced. However, the variation in VF susceptibility in female rat hearts that is associated with the different stages of the estrous cycle may affect statistical power that could potentially lead to Type II statistical errors. This problem can be prevented with careful randomization. (C) 2013 Elsevier Inc. All rights reserved.