This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Muscle wasting is a common feature of both chronic alcohol consumption and AIDS. According to the CDC, involuntary weight loss greater than 10% in an HIV-infected individual is a hallmark of AIDS. Despite the significant improvement in control of HIV-infection with the use of highly active anti-retroviral therapy, the AIDS wasting syndrome and the resulting decline in body cell mass remains a major cause of morbidity and mortality. Excess alcohol consumption is associated with a 50% incidence of skeletal muscle myopathy resulting from decreased muscle protein synthesis as well as accelerated muscle proteolysis. The effects of alcohol consumption on muscle metabolism appear to be multifactorial. The hypothesis to be tested by the specific aims described in this proposal is that chronic alcohol administration accelerates the progression and exacerbates the severity of muscle wasting associated with simian immunodeficiency virus (SIV) infection by altering the balance between protein anabolic and catabolic mechanisms. The general aim of the studies proposed is to determine the impact of chronic alcohol administration on the temporal progression of whole body, tissue and molecular alterations in body composition, muscle mass and muscle protein synthesis and breakdown, in SIV-infected rhesus monkeys. This study has and continues to 1) determine body composition throughout the course of SIV infection in chronically alcohol-administered monkeys and in parallel, the in vivo rates of muscle protein synthesis and breakdown, as well as, 2) the rate-controlling molecular mechanisms involved in both synthetic (eukaryotic initiation factors, myostatin) and degradation (ubiquitin-proteasome) pathways and 3) the recognized endocrine (IGF-I, GH, insulin & testosterone) nutritional (amino acids) and immune (pro-inflammatory cytokines) modulators of muscle mass. We are currently using muscle biopsies and DEXA scanning to aid in determining these factors. The results from these studies will provide detailed knowledge of how alcohol and SIV independently as well as in concert thereby impair the host s cellular metabolic and synthetic mechanisms involved in the regulation of muscle mass. To date we have three animals remaining on the study. One animal shows no indication of infection or viral load and the remaining two progressive SAIDS.
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