Fasted plasma asprosin concentrations are associated with menstrual cycle phase, oral contraceptive use and training status in healthy women.

PURPOSE: Asprosin, an orexigenic hormone that stimulates hepatic glucose release, is elevated in insulin resistance and associated with obesity. Plasma asprosin concentrations may also be related to female sex hormone levels; higher levels are reported in women with polycystic ovary syndrome (PCOS) but this may be related to peripheral insulin resistance also associated with PCOS. Clarification of female-specific factors influence on the plasma asprosin response is crucial for studies investigating asprosin. Therefore, this study determined the association of menstrual phase, oral contraceptive (OC) use (as a pharmacological influence on sex hormone levels) and training status (as a physiological influence on sex hormone levels) on plasma asprosin levels in pre-menopausal women. METHODS: Fasting plasma asprosin, 17ß-estradiol (E2) and progesterone, were assessed in 32 healthy untrained and trained women with regular menstrual cycles (non-OC; n = 8 untrained, n = 6 trained) or using OC (n = 10 untrained, n = 8 trained) during early follicular, late follicular and mid-luteal menstrual phases (or the time-period equivalent for OC users). RESULTS: Asprosin was lower in OC (0.75 ± 0.38 ng mL-1) than non-OC users (1.00 ± 0.37 ng mL-1; p = 0.022). Across a cycle, asprosin was highest in the early follicular equivalent time-point in OC users (0.87 ± 0.37 ng mL-1) but highest in the mid-luteal phase in non-OC users (1.09 ± 0.40 ng mL-1). Asprosin concentrations varied more across a cycle in untrained than trained women, with higher concentrations in the early follicular phase compared to the late follicular and mid-luteal (training status-by-menstrual phase interaction p = 0.028). CONCLUSION: These findings highlight the importance of considering OC use, menstrual cycle phase and to a lesser extent training status when investigating circulating asprosin concentrations in females.

Bioengineered human skeletal muscle capable of functional regeneration.

BACKGROUND: Skeletal muscle (SkM) regenerates following injury, replacing damaged tissue with high fidelity. However, in serious injuries, non-regenerative defects leave patients with loss of function, increased re-injury risk and often chronic pain. Progress in treating these non-regenerative defects has been slow, with advances only occurring where a comprehensive understanding of regeneration has been gained. Tissue engineering has allowed the development of bioengineered models of SkM which regenerate following injury to support research in regenerative physiology. To date, however, no studies have utilised human myogenic precursor cells (hMPCs) to closely mimic functional human regenerative physiology. RESULTS: Here we address some of the difficulties associated with cell number and hMPC mitogenicity using magnetic association cell sorting (MACS), for the marker CD56, and media supplementation with fibroblast growth factor 2 (FGF-2) and B-27 supplement. Cell sorting allowed extended expansion of myogenic cells and supplementation was shown to improve myogenesis within engineered tissues and force generation at maturity. In addition, these engineered human SkM regenerated following barium chloride (BaCl2) injury. Following injury, reductions in function (87.5%) and myotube number (33.3%) were observed, followed by a proliferative phase with increased MyoD+ cells and a subsequent recovery of function and myotube number. An expansion of the Pax7+ cell population was observed across recovery suggesting an ability to generate Pax7+ cells within the tissue, similar to the self-renewal of satellite cells seen in vivo. CONCLUSIONS: This work outlines an engineered human SkM capable of functional regeneration following injury, built upon an open source system adding to the pre-clinical testing toolbox to improve the understanding of basic regenerative physiology.

Screening for viral hepatitis prior to rituximab chemotherapy.

In 2008, the CDC published guidelines recommending screening of all persons undergoing treatment with rituximab to identify persons at risk of hepatitis B virus (HBV) reactivation. We evaluated implementation of this recommendation in veterans, who are at increased risk of HBV, and determined characteristics of those screened. We also evaluated a control setting, rates of hepatitis C virus (HCV) screening among the same rituximab-treated patients. There are no guidelines that recommend HCV screening prior to initiation of rituximab. Medical records of patients receiving rituximab between January 2006 and December 2012 were reviewed according to two time periods: 2006-2008 (period 1, pre-guidelines) and 2009-2012 (period 2, post-guidelines). Patient demographics, concomitant chemotherapy regimen (protocol, dose, duration), treatment indication, risk factors for hepatitis infection (substance abuse, homelessness, human immunodeficiency virus (HIV)), and HBV/HCV screening status were documented. During the study period, 102 patients were treated with rituximab (49 in period 1 and 53 in period 2). During periods 1 and 2, 22 and 32 % of rituximab-treated patients were screened for HBV, respectively (p = 0.375). Treatment during 2009 was the only significant predictor of HBV screening in the adjusted model (p = 0.01). For HCV during periods 1 and 2, 22 and 21 % of patients were screened, respectively (p = 1.00). There were no significant predictors of HCV screening. Rates of screening for HBV among rituximab-treated patients were low, both before and after dissemination of guidelines recommending universal HBV screening of rituximab-treated patients.

Submicellar bile salts stimulate phosphatidylcholine transfer activity of sterol carrier protein 2.

To explore a potential role for sterol carrier protein 2 (SCP2, also known as non-specific lipid transfer protein) in hepatocellular phospholipid trafficking, we examined the influence of submicellar bile salt concentrations on phosphatidylcholine (PC) transfer activity of SCP2. We measured rate constants for first-order transfer of sn-1 palmitoyl, sn-2 parinaroyl PC, a naturally fluorescent self-quenching phospholipid between model membranes. Purified bovine liver SCP2 promoted transfer of PC from donor to acceptor small unilamellar vesicles. Taurine- and glycine-conjugated bile salts (anionic steroid detergent-like molecules), at concentrations well below their critical micellar concentrations, stimulated PC transfer activity of SCP2 80- to 140-fold. Rate constants increased in proportion to bile salt concentration, temperature, and bile salt-membrane binding affinity. Sodium taurofusidate, a conjugated fungal bile salt analog, also activated PC transfer whereas no effect was observed with the anionic and non-ionic straight chain detergents sodium dodecyl sulfate and octylglucoside, respectively. Thermodynamic and kinetic analyses of PC transfer support a mechanism in which bile salts stimulate SCP2 activity by partitioning into donor vesicles and enhancing membrane association of SCP2. These results imply that under physiological conditions, SCP2 may contribute to hepatocellular selection and transport of biliary PCs.