The goal of the proposal is to examine the general hypothesis that testosterone normalization in the burned patients will ameliorate the severe net catabolic state of the skeletal muscle and promote recovery during both the acute and the recovery phases of the burn treatment. The efficiency of testosterone normalization will be addressed by the rate of protein synthesis and breakdown, lean body mass, muscle mass and muscular strength. Protein synthesis and breakdown in the skeletal muscle will be determined by two independent methods using stable isotope tracers: either a direct incorporation of isotopes into the proteins, or an A-V balance model of both tracer and tracee combined with muscle biopsy to evaluate the enrichment of the tracers in the muscle. The studies will be conducted in burn patients during their acute phase of hospitalization, with the control study conducted about one week after admission and the intervention study after 2-3 weeks of testosterone injection. The studies will also be conducted in three convalescent groups of burn patients receiving: (a) standard rehabilitation; (b) testosterone + standard rehabilitation and (c), testosterone + resistance exercises throughout two months of rehabilitation. These studies will provide new insight into the anabolic effects of testosterone normalization on the regulation and repair of burn injury-induced skeletal muscle protein metabolisms during both acute and rehabilitation phases of burn treatment.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM057295-03
Application #
6180512
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Program Officer
Somers, Scott D
Project Start
1998-05-01
Project End
2001-06-30
Budget Start
2000-05-02
Budget End
2001-06-30
Support Year
3
Fiscal Year
2000
Total Cost
$213,411
Indirect Cost
Name
University of Texas Medical Br Galveston
Department
Surgery
Type
Schools of Medicine
DUNS #
041367053
City
Galveston
State
TX
Country
United States
Zip Code
77555
Tuvdendorj, Demidmaa; Chinkes, David L; Zhang, Xiao-Jun et al. (2011) Adult patients are more catabolic than children during acute phase after burn injury: a retrospective analysis on muscle protein kinetics. Intensive Care Med 37:1317-22
Tuvdendorj, Demidmaa; Chinkes, David L; Zhang, Xiao-Jun et al. (2011) Skeletal muscle is anabolically unresponsive to an amino acid infusion in pediatric burn patients 6 months postinjury. Ann Surg 253:592-7
Cree, Melanie G; Paddon-Jones, Douglas; Newcomer, Bradley R et al. (2010) Twenty-eight-day bed rest with hypercortisolemia induces peripheral insulin resistance and increases intramuscular triglycerides. Metabolism 59:703-10
Ferrando, Arny A; Wolfe, Robert R (2007) Restoration of hormonal action and muscle protein. Crit Care Med 35:S630-4
Uchakin, Peter N; Stowe, Raymond P; Paddon-Jones, Douglas et al. (2007) Cytokine secretion and latent herpes virus reactivation with 28 days of horizontal hypokinesia. Aviat Space Environ Med 78:608-12
Workeneh, Biruh T; Rondon-Berrios, Helbert; Zhang, Liping et al. (2006) Development of a diagnostic method for detecting increased muscle protein degradation in patients with catabolic conditions. J Am Soc Nephrol 17:3233-9
Paddon-Jones, Douglas; Sheffield-Moore, Melinda; Katsanos, Christos S et al. (2006) Differential stimulation of muscle protein synthesis in elderly humans following isocaloric ingestion of amino acids or whey protein. Exp Gerontol 41:215-9
Paddon-Jones, Douglas; Sheffield-Moore, Melinda; Cree, Melanie G et al. (2006) Atrophy and impaired muscle protein synthesis during prolonged inactivity and stress. J Clin Endocrinol Metab 91:4836-41
Paddon-Jones, Douglas; Wolfe, Robert R; Ferrando, Arny A (2005) Amino acid supplementation for reversing bed rest and steroid myopathies. J Nutr 135:1809S-1812S
Paddon-Jones, Douglas; Sheffield-Moore, Melinda; Urban, Randall J et al. (2005) The catabolic effects of prolonged inactivity and acute hypercortisolemia are offset by dietary supplementation. J Clin Endocrinol Metab 90:1453-9

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