Erythropoietin Does Not Enhance Skeletal Muscle Protein Synthesis Following Exercise in Young and Older Adults

PURPOSE: Erythropoietin (EPO) is a renal cytokine that is primarily involved in hematopoiesis while also playing a role in non-hematopoietic tissues expressing the EPO-receptor (EPOR). The EPOR is present in human skeletal muscle. In mouse skeletal muscle, EPO stimulation can activate the AKT serine/threonine kinase 1 (AKT) signaling pathway, the main positive regulator of muscle protein synthesis. We hypothesized that a single intravenous EPO injection combined with acute resistance exercise would have a synergistic effect on skeletal muscle protein synthesis via activation of the AKT pathway. METHODS: Ten young (24.2 ± 0.9 years) and 10 older (66.6 ± 1.1 years) healthy subjects received a primed, constant infusion of [ring-13C(6)] L-phenylalanine and a single injection of 10,000 IU epoetin-beta or placebo in a double-blind randomized, cross-over design. 2 h after the injection, the subjects completed an acute bout of leg extension resistance exercise to stimulate skeletal muscle protein synthesis. RESULTS: Significant interaction effects in the phosphorylation levels of the members of the AKT signaling pathway indicated a differential activation of protein synthesis signaling in older subjects when compared to young subjects. However, EPO offered no synergistic effect on vastus lateralis mixed muscle protein synthesis rate in young or older subjects. CONCLUSIONS: Despite its ability to activate the AKT pathway in skeletal muscle, an acute EPO injection had no additive or synergistic effect on the exercise-induced activation of muscle protein synthesis or muscle protein synthesis signaling pathways

Reduced pelvic pain in women with endometriosis: efficacy of long-term dienogest treatment

Purpose To investigate the efficacy and safety of dienogest as a long-term treatment in endometriosis, with follow-up after treatment discontinuation. The study included women with endometriosis, who had previously completed a 12-week, placebo-controlled study of dienogest, who participated in an open-label extension study for up to 53 weeks. Thereafter, a patient subgroup was evaluated in a 24-week follow-up after treatment discontinuation. Methods A multicenter study performed in Germany, Italy and Ukraine. Women with endometriosis were enrolled at completion of the placebo-controlled study (n = 168). All women received dienogest (2 mg once daily, orally) and changes in pelvic pain (on a visual analog scale), bleeding pattern, adverse events and laboratory parameters were evaluated during and after treatment. Results The completion rate among women who entered the open-label extension study was 90.5% (n = 152). A Significant decrease in pelvic pain was shown during continued dienogest treatment (P < 0.001). The mean frequency and intensity of bleeding progressively decreased. Adverse events, rated generally mild or moderate, led to withdrawal in four patients (2.4%). No clinically relevant changes in laboratory parameters were observed. During treatmentfree follow-up (n = 34), the reduction in pelvic pain persisted, while bleeding frequency and intensity returned to normal patterns. Conclusions Long-term dienogest showed a favorable efficacy and safety profile, with progressive decreases in pain and bleeding irregularities during continued treatment; the decrease of pelvic pain persisted for at least 24 weeks after treatment cessation. © Springer-Verlag 2011

Numerical Investigation of Space Launch Vehicle Base Flows with Hot Plumes

The flow field around generic space launch vehicles with hot exhaust plumes is investigated numerically. Reynolds-Averaged Navier-Stokes (RANS) simulations are thermally coupled to a structure solver to allow determination of heat fluxes into and temperatures in the model structure. The obtained wall temperatures are used to accurately investigate the mechanical and thermal loads using Improved Delayed Detached Eddy Simulations (IDDES) as well as RANS. The investigated configurations feature cases both with cold air and hot hydrogen/water vapour plumes as well as cold and hot wall temperatures. It is found that the presence of a hot plume increases the size of the recirculation region and changes the pressure distribution on the nozzle structure and thus the loads experienced by the vehicle. The same effect is observed when increasing the wall temperatures. Both RANS and IDDES approaches predict the qualitative changes between the configurations, but the reattachment location predicted by IDDES is up to 7% further upstream than that predicted by RANS. Additionally, the heat flux distribution along the nozzle and base surface is analysed and shows significant discrepancies between RANS and IDDES, especially on the nozzle surface and in the base corner

Computational Cancer Biology: An Evolutionary Perspective

ISSN:1553-734XISSN:1553-735