The goal of this proposal is to investigate the general hypothesis that recombinant growth hormone and/or oxandrolone (testosterone) will increase net skeletal muscle protein synthesis and decrease the net efflux of intracellular amino acids in recovering burned children. A further goal of this project is to investigate the hypothesis that the effects of these anabolic agents will be amplified by increased inward amino acid transport. Interventions promoting inward amino acid transport, such as amino acid infusion, or synthetic efficiency, such as exercise, will be investigated in conjunction with administration of these anabolic agents. Finally, we will investigate the hypothesis that amelioration of hyper- coritsolemia will reduce muscle protein breakdown and result in a greater net protein balance with these anabolic agents. This proposal will evaluate the efficacy of these anabolic agents and determine the direction of future intervention studies. In order to simultaneously quantify the rates of muscle protein synthesis and breakdown, a new model will be used that involves the use of tracers of amino acids labeled with stable isotopes and the measurement of intracellular free and protein-bound amino acid enrichments. This unique methodology allows the direct determination in vivo of muscle protein synthesis and breakdown in skeletal muscle. We will also utilize a second model that relies on arterial-venous differences to independently determine muscle protein synthesis, breakdown, and tissue amino acid transport. This combination of methodologies allows us to independently confirm the effects of these proposed interventions on muscle protein. In addition, we will determine interventional effects on the responses of myofibrillar and mitochondrial protein fractions. The effects of anabolic agents on muscle protein synthesis in burned children will be assessed by comparing standard care to children rehabilitated with a defined """"""""in-house"""""""" exercise program. Further, we will address the interactive effects of acute anabolic agents and exercise on skeletal muscle protein synthesis and breakdown, and amino acid kinetics in children 9 months post-burn. These studies will provide insight into the synthetic mechanisms affected by anabolic agents, amino acids and exercise in this unique population.
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