Activation of the beta 2AR in cultured keratinocytes signals the down-regulation of the AKT pathway, accompanied by a stabilization of the actin cytoskeleton and an increase in focal adhesion formation, resulting in a nonmigratory phenotype. Burn wound injury in excised human skin also rapidly up-regulates the intra-epithelial expression
of the epinephrine synthesizing enzyme phenylethanolamine-N-methyltransferase, SCH 900776 purchase and tissue levels of epinephrine rise dramatically (15-fold) in the burn wounded tissue (values of epinephrine expressed as pg/ug protein +/- standard error of the mean: unburned control, 0.6 +/- 0.36; immediately postburn, 9.6 +/- 1.58; 2 h postburn, 3.1 +/- 1.08; 24 h post-burn, 6.7 +/- 0.94). Finally, using an animal burn wound model (20% body surface in mice), we found that systemic treatment with beta AR antagonists results in a significant increase (44%, 95% CI 27%-61%, p < 0.00000001) in the rate of burn wound re-epithelialization.
Conclusions This work demonstrates an alternate pathway by which stress can impair healing: by stress-induced elevation of epinephrine levels resulting in activation of the keratinocyte beta 2AR and the impairment of cell otility and wound re-epithelialization. Furthermore, since the burn wound locally generates epinephrine in
response to wounding, epinephrine levels are locally, as well as systemically, AMPK inhibitor elevated, and wound healing is impacted by these dual mechanisms. Treatment with beta adrenergic antagonists significantly improves the rate of burn wound re-epithelialization. This work suggests that specific beta 2AR antagonists may be apt, near-term translational therapeutic targets for enhancing burn wound healing, and may provide a novel, low-cost, safe approach GS-9973 molecular weight to improving skin wound repair in the stressed individual.”
“Background: The absorption of cocoa flavanols in the small intestine is limited, and the majority of the flavanols reach the
large intestine where they may be metabolized by resident microbiota.
Objective: We assessed the prebiotic potential of cocoa flavanols in a randomized, double-blind, crossover, controlled intervention study.
Design: Twenty-two healthy human volunteers were randomly assigned to either a high-cocoa flavanol (HCF) group (494 mg cocoa flavanols/d) or a low-cocoa flavanol (LCF) group (23 mg cocoa flavanols/d) for 4 wk. This was followed by a 4-wk washout period before volunteers crossed to the alternant arm. Fecal samples were recovered before and after each intervention, and bacterial numbers were measured by fluorescence in situ hybridization. A number of other biochemical and physiologic markers were measured.
Results: Compared with the consumption of the LCF drink, the daily consumption of the HCF drink for 4 wk significantly increased the bifidobacterial (P<0.01) and lactobacilli (P<0.001) populations but significantly decreased clostridia counts (P<0.001).