Influence of menopause status and age on integrated central and peripheral hemodynamic responses to subsystolic cuffing during submaximal exercise.

Although pathophysiological links between postmenopause and healthy aging remain unclear, both factors are associated with increased blood pressure and sympathetic nerve activity (SNA) in women. Activation of polymodal musculoskeletal neural afferents originating within adventia of venules modulates SNA and blood pressure control during exercise in healthy adults. We hypothesized transient subsystolic regional circulatory occlusion (RCO) during exercise sensitizes these afferents leading to augmented systemic vascular resistance (SVR)-mediated increased mean arterial pressure (MAP) in postmenopause vs.

Evaluation of a dosing regimen for continuous vancomycin infusion in critically ill patients: an observational study in intensive care unit patients.

Purpose: We aimed to evaluate a dosing algorithm for continuous vancomycin administration in intensive care unit patients.

Materials And Methods: This observational study was conducted in a medical intensive care unit (German university hospital; June 2012-February 2013). Following a loading dose of 20 mg per kg actual body weight, vancomycin was administered continuously (20 or 30 mg of vancomycin per kg actual body weight over 24 hours depending on renal function).

BAD and glucokinase reside in a mitochondrial complex that integrates glycolysis and apoptosis.

Glycolysis and apoptosis are considered major but independent pathways that are critical for cell survival. The activity of BAD, a pro-apoptotic BCL-2 family member, is regulated by phosphorylation in response to growth/survival factors. Here we undertook a proteomic analysis to assess whether BAD might also participate in mitochondrial physiology.

Lactacystin and clasto-lactacystin beta-lactone modify multiple proteasome beta-subunits and inhibit intracellular protein degradation and major histocompatibility complex class I antigen presentation.

The antibiotic lactacystin was reported to covalently modify beta-subunit X of the mammalian 20 S proteasome and inhibit several of its peptidase activities. However, we demonstrate that [3H]lactacystin treatment modifies all the proteasome's catalytic beta-subunits. Lactacystin and its more potent derivative beta-lactone irreversibly inhibit protein breakdown and the chymotryptic, tryptic, and peptidylglutamyl activities of purified 20 S and 26 S particles, although at different rates.

Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class I molecules.

Reagents that inhibit the ubiquitin-proteasome proteolytic pathway in cells have not been available. Peptide aldehydes that inhibit major peptidase activities of the 20S and 26S proteasomes are shown to reduce the degradation of protein and ubiquitinated protein substrates by 26S particles. Unlike inhibitors of lysosomal proteolysis, these compounds inhibit the degradation of not only abnormal and short-lived polypeptides but also long-lived proteins in intact cells.