The melanocortin (MC) system is a pivotal component of the hypothalamo-pituitary-adrenal (HPA) stress axis and plays an important role in the pathogenesis of obesity and the metabolic syndrome. Adipose dysfunction is implicated in the pathogenesis of these disorders. We investigated direct ACTH effects on adipose functions in immortalised murine white and brown adipocytes. MC receptor types 2 and 5 were expressed at the mRNA and protein levels and were strongly up-regulated during differentiation. Chronic ACTH stimulation did not affect adipogenesis. Insulin-induced glucose uptake in white adipocytes was acutely and transiently reduced by 45% upon ACTH treatment. Visfatin and adiponectin gene expression was reduced by about 50% in response to ACTH, while interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) mRNA levels were acutely up-regulated by 2100 and 60% respectively. Moreover, IL-6 secretion was increased by 1450% within 4 h of ACTH treatment. In brown adipocytes, stimulation with ACTH caused a 690% increase in uncoupling protein (UCP)-1 mRNA levels within 8 h, followed by a 470% increase in UCP-1 protein concentrations after 24 h. Consistently, p38 mitogen-activated protein kinase (MAPK) phosphorylation was acutely increased by 1800% in response to ACTH stimulation, and selective inhibition of p38 MAPK abolished the ACTH-mediated UCP-1 protein increase. Taken together, ACTH acutely promotes an insulinresistant, pro-inflammatory state and transiently enhances energy combustion. In conditions characterised by a dysregulation of the HPA stress axis such as the metabolic syndrome, direct MC interaction with adipocytes may contribute to dysregulated energy balance, insulin resistance and cardiometabolic complications.
Nerve conduits are nonneural, hollow tubular structures designed to bridge the gap of a sectioned nerve, to protect the nerve from scar formation, and to guide the regenerating fibers into the distal nerve stump. In the 8-year experience of our department, four patients aged 14 to 50 years had an unsuccessful implantation of a nerve conduit (NeuraGen, Integra, Plainsboro, NJ). In these four patients, the collagen tubes were replaced by an autogenous nerve graft. The histological specimens showed characteristic histological findings of a scar neuroma without any signs of foreign body reaction in three cases and with minimal foreign body reaction in one case. The collagen nerve tube was completely resorbed in all cases after a time period of 6 to 17 months and could not be detected marco- or microscopically.To our knowledge, this is the first report in the English and German literature describing the histological characteristics of explanted collagen nerve tubes in humans.
For a successful outcome of the burned hand, the interdisciplinary involvement and cooperation of the plastic and pediatric surgeon, hand therapist, burn team, patient and their parents are crucial.
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