Improved Net Protein Balance, Lean Mass, and Gene Expression Changes With Oxandrolone Treatment in the Severely Burned

ObjectiveTo determine the effects of the anabolic agent oxandrolone on muscle protein and gene expression in severely burned children. Summary Background DataThe authors previously showed that oxandrolone increased net muscle protein synthesis in emaciated burned patients receiving delayed treatment for severe burns. They hypothesized that similar effects would be seen in those treated early after burn. MethodsThirty-two severely burned children were enrolled in a prospective randomized trial. Subjects underwent studies to assess leg protein net balance 5 days after the first excision and grafting procedure. Immediately after these studies, treatment with placebo (n = 18) or 0.1 mg/kg oxandrolone (n = 14) twice a day was started. One week after this, another net balance study was performed in each subject. Body weights and total body potassium counting were used to determine body compositional changes. Muscle biopsies were taken 1 week after treatment in oxandrolone subjects to examine gene expression changes with gene array (12,600 genes). ResultsProtein net balance did not change in the placebo group, while oxandrolone-treated subjects had a significant improvement. Body weights and fat free mass significantly decreased in the placebo group, while no changes were found in the oxandrolone-treated subjects. Expression changes were seen in 14 genes in the oxandrolone group compared to placebo. Some of these included myosin light chain (+2.7-fold change), tubulin (+2.3), calmodulin (−2.3), and protein phosphatase I inhibitor (−2.8). ConclusionsOxandrolone improves protein net balance and lean mass in the severely burned. These changes are associated with increased gene expression for functional muscle proteins.

[1]  P. M. Reid,et al.  Body cell mass repletion and improved quality of life in HIV-infected individuals receiving oxandrolone. , 2002, JPEN - Journal of Parenteral and Enteral Nutrition.

[2]  R. Wolfe,et al.  The effect of prolonged euglycemic hyperinsulinemia on lean body mass after severe burn. , 2002, Surgery.

[3]  S. Yeh,et al.  Reversal of COPD-associated weight loss using the anabolic agent oxandrolone. , 2002, Chest.

[4]  K. Davies,et al.  The DSCR1 (Adapt78) isoform 1 protein calcipressin 1 inhibits calcineurin and protects against acute calcium‐mediated stress damage, including transient oxidative stress , 2002, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[5]  G. Pavlath,et al.  Calcineurin differentially regulates maintenance and growth of phenotypically distinct muscles. , 2002, American journal of physiology. Cell physiology.

[6]  N. Stahnke,et al.  Favorable Final Height Outcome in Girls with Ullrich-Turner Syndrome Treated with Low-Dose Growth Hormone Together with Oxandrolone Despite Starting Treatment After 10 Years of Age , 2002, Journal of pediatric endocrinology & metabolism : JPEM.

[7]  S. Dudoit,et al.  STATISTICAL METHODS FOR IDENTIFYING DIFFERENTIALLY EXPRESSED GENES IN REPLICATED cDNA MICROARRAY EXPERIMENTS , 2002 .

[8]  R. Wolfe,et al.  Testosterone administration in severe burns ameliorates muscle catabolism , 2001, Critical care medicine.

[9]  D. Chinkes,et al.  Anabolic Effects of Oxandrolone After Severe Burn , 2001, Annals of surgery.

[10]  C. Li,et al.  Model-based analysis of oligonucleotide arrays: expression index computation and outlier detection. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[11]  D. Chinkes,et al.  Determinants of Skeletal Muscle Catabolism After Severe Burn , 2000, Annals of surgery.

[12]  D. Chinkes,et al.  Persistence of muscle catabolism after severe burn. , 2000, Surgery.

[13]  D. Schoenfeld,et al.  Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. , 2000, The New England journal of medicine.

[14]  D. Orgill,et al.  The anticatabolic and wound healing effects of the testosterone analog oxandrolone after severe burn injury. , 2000, Journal of critical care.

[15]  D. Chinkes,et al.  Anabolic effects of insulin-like growth factor in combination with insulin-like growth factor binding protein-3 in severely burned adults. , 1999, The Journal of trauma.

[16]  C. K. Lee,et al.  Gene expression profile of aging and its retardation by caloric restriction. , 1999, Science.

[17]  Richard P. Harvey,et al.  Skeletal muscle hypertrophy is mediated by a Ca2+-dependent calcineurin signalling pathway , 1999, Nature.

[18]  A. Musarò,et al.  IGF-1 induces skeletal myocyte hypertrophy through calcineurin in association with GATA-2 and NF-ATc1 , 1999, Nature.

[19]  R. Wolfe,et al.  The Journal of Clinical Endocrinology & Metabolism Printed in U.S.A. Copyright © 1999 by The Endocrine Society Short-Term Oxandrolone Administration Stimulates Net Muscle Protein Synthesis in Young Men* , 2022 .

[20]  D. Chinkes,et al.  Muscle protein catabolism after severe burn: effects of IGF-1/IGFBP-3 treatment. , 1999, Annals of surgery.

[21]  R. Demling,et al.  Comparison of the anabolic effects and complications of human growth hormone and the testosterone analog, oxandrolone, after severe burn injury. , 1999, Burns : journal of the International Society for Burn Injuries.

[22]  D. Chinkes,et al.  A submaximal dose of insulin promotes net skeletal muscle protein synthesis in patients with severe burns. , 1999, Annals of surgery.

[23]  X. Estivill,et al.  Genomic organization, alternative splicing, and expression patterns of the DSCR1 (Down syndrome candidate region 1) gene. , 1997, Genomics.

[24]  R. Demling,et al.  Oxandrolone, an anabolic steroid, significantly increases the rate of weight gain in the recovery phase after major burns. , 1997, The Journal of trauma.

[25]  D. Simpson,et al.  Oxandrolone in AIDS‐wasting myopathy , 1996, AIDS.

[26]  R. Wolfe,et al.  Herman Award Lecture, 1996: relation of metabolic studies to clinical nutrition--the example of burn injury. , 1996, The American journal of clinical nutrition.

[27]  M. Hochstrasser Ubiquitin-dependent protein degradation. , 1996, Annual review of genetics.

[28]  K Tanaka,et al.  Structure and functions of the 20S and 26S proteasomes. , 1996, Annual review of biochemistry.

[29]  D. Wilson,et al.  Oxandrolone therapy in constitutionally delayed growth and puberty. Bio-Technology General Corporation Cooperative Study Group. , 1995, Pediatrics.

[30]  D. Chinkes,et al.  Stimulation of Muscle Protein Synthesis by Long‐Term Insulin Infusion in Severely Burned Patients , 1995, Annals of surgery.

[31]  G. Biolo,et al.  Increased rates of muscle protein turnover and amino acid transport after resistance exercise in humans. , 1995, The American journal of physiology.

[32]  D. Wilmore,et al.  Increased survival after major thermal injury: the effect of growth hormone therapy in adults. , 1995, The Journal of trauma.

[33]  L. Rue,et al.  Insulin‐Like Growth Factor‐1 Lowers Protein Oxidation in Patients with Thermal Injury , 1994, Annals of surgery.

[34]  R. Wolfe,et al.  Acute response of human muscle protein to catabolic hormones. , 1993, Annals of surgery.

[35]  R. Bower Nutrition during critical illness and sepsis. , 1993, New Horizons.

[36]  K. Ellis,et al.  Total body potassium in the infant , 1992 .

[37]  G. Biolo,et al.  Harry M. Vars Research Award. A new model to determine in vivo the relationship between amino acid transmembrane transport and protein kinetics in muscle. , 1992, JPEN. Journal of parenteral and enteral nutrition.

[38]  R. Wolfe,et al.  Effect of exogenous growth hormone on whole-body and isolated-limb protein kinetics in burned patients. , 1991, Archives of surgery.

[39]  D. Herndon,et al.  Comparison of resting energy expenditures and caloric intake in children with severe burns. , 1990, The Journal of burn care & rehabilitation.

[40]  P. Chomczyński,et al.  Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. , 1987, Analytical biochemistry.

[41]  A. Beddoe,et al.  Aggressive nutritional support does not prevent protein loss despite fat gain in septic intensive care patients. , 1987, The Journal of trauma.

[42]  D. Wilmore,et al.  Combined Hormonal Infusion Simulates the Metabolic Response to Injury , 1984, Annals of surgery.

[43]  A. Mason,et al.  Weight Loss Following Thermal Injury , 1973, Annals of surgery.