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Propranolol, a nonselective [[beta].sub.2]-blocker, has been shown effective in hypermetabolic burn patients by decreasing cardiac work, protein catabolism, and lipolysis. This study investigates the effect of propranolol on gene and protein expression changes in skeletal muscle of burned children by use of high-density oligonucleotide arrays to establish the genetic profiles and stable isotope technique to quantitate protein synthesis. Thirty-seven children (mean age 9.7 [+ or -] 1.1 yr) were randomized into groups to receive placebo (n = 23) or propranolol (n = 14) titrated to reduce heart rate by 15%. Children had >40% total body surface area burns (mean 43 [+ or -] 5.6%). Protein net balance was determined by stable-isotope infusion technique. Total RNA from muscle biopsies was isolated, labeled, and cRNA hybridized to the HG-U95Av2 Affymetrix array. Mean net balance of protein synthesis and breakdown was -14.3 [+ or -] 12.9 nmol*[min.sup.-1]* 100 ml leg [volume.sup.-1] for placebo and +69.3 [+ or -] 34.9 nmol*[min.sup.-1]*100 ml leg [volume.sup.-1] in the propranolol-treated children (P = 0.012). Comparison of 12,000 genes in burned children receiving placebo showed increased expression of two genes with time, whereas children receiving propranolol showed increased expression of nine genes with a decrease in five genes. We conclude that burned children receiving propranolol showed a significant upregulation in genes involved in muscle metabolism and downregulation of an important enzyme involved in gluconeogenesis and insulin resistance compared with burned children receiving placebo. The upregulation of genes involved in muscle metabolism correlates well with the increase in net protein balance across the leg. propranolol; microarray analysis; hypermetabolism; muscle catabolism

The events occurring early in the burn wound trigger a sequence of local and systemic responses that influence cell and tissue survival and, consequently, wound healing and recovery. Using high-density oligonucleotide arrays we identified gene expression patterns in skin samples taken from a region of injury in the burn rat model. The associated genomic events include the differential expression of genes involved in cell survival and death, cell growth regulation, cell metabolism, inflammation, and immune response. The functional gene cluster detected and their time appearance matched the time sequence known to occur in burn wound healing. gene expression profile; microarray; wound healing; skin; rat burn model

The role of plasma free fatty acids and de novo synthesized fatty acids in the synthesis of lung surfactant phosphatidylcholine (PC) has been studied. A new stable isotope tracer model was used in infusing (1,2-13C2)acetate and uniformly labeled (U-13C16)palmitate in nine overnight fasted pigs. Surfactant kinetics were measured during the basal state and during low-dose glucose infusion. Results indicate glucose does not affect PC synthesis. Plasma is also the main contributor of fatty acids for surfactant PC synthesis.

Thermal injury has been shown to alter gut epithelium and heart myocyte homeostasis by inducing programmed cell death. The effect of thermal injury on hepatocyte apoptosis and proliferation, however, has not been established. The purpose of this study was to determine whether a large thermal injury increases liver cell apoptosis and proliferation and whether these changes were associated with alterations in hepatic nuclear factor [Kappa]B (NF-[Kappa]B) expression and changes in liver enzymes and amount of protein. Sprague-Dawley rats received a 40% total body surface area scald burn or sham burn. Rats were killed and livers were harvested at 1, 2, 5, and 7 days after burn. Liver cell apoptosis was determined by terminal deoxyuridine nick end labeling (TUNEL) assay and cell proliferation by immunohistochemistry for proliferating cell nuclear antigen. Hepatic NF-[Kappa]B expression was determined by Western blot, and total hepatic protein content was determined by protein assay. Protein concentration decreased after burn compared with sham controls (P [is less than] 0.05). Liver cell apoptosis, proliferation, and NF-[Kappa]B expression in hepatocytes increased in burned rats compared with controls (P [is less than] 0.05). It was concluded that thermal injury induces hepatic cell apoptosis and proliferation associated with an increase in hepatic NF-[Kappa]B expression and a decrease in hepatic protein concentration. thermal injury; hepatic cells.

Martini, Wenjun Z., Oivind Irtun, David L. Chinkes, Robert E. Barrow, and Robert R. Wolfe. Glucose effects on lung surfactant kinetics in conscious pigs. Am J Physiol Endocrinol Metab 279: E920-E926, 2000.--The primary goal of this study was to investigate the effects of glucose infusion on surfactant phosphatidylcholine (PC) metabolic kinetics in the lungs. A new stable isotope tracer model was used in which [1,2-[sup.13][C.sub.2]]acetate and uniformly labeled [U-[sup.13][C.sub.16]]palmitate were infused in 12 normal overnight-fasted pigs to quantify lung surfactant kinetics with or without glucose infusion (24 mg [multiplied by] [kg.sup.-1] [multiplied by] [min.sup.-1]). With glucose infusion, the rate of surfactant PC incorporation from de novo synthesized palmitate increased from the control value of 2.1 [+ or -] 0.2 to 15.5 [+ or -] 1.9 nmol PC-bound palmitate [multiplied by] [h.sup.-1] [multiplied by] g wet [lung.sup.-1] (P [is less than] 0.05), whereas the incorporation rate from plasma preformed palmitate decreased from the control value of 20.9 [+ or -] 1.9 to 11.6 [+ or -] 1.1 nmol palmitate [multiplied by] [h.sup.-1] [multiplied by] g wet [lung.sup.-1] (P [is less than] 0.05). The palmitate composition in lamellar body surfactant PC increased from the control value of 61.7 [+ or -] 2.1% to 75.9 [+ or -] 0.6% (P [is less than] 0.05). The surfactant PC secretion rate decreased from the control value of 239.0 [+ or -] 26.1 to 81.9 [+ or -] 5.3 nmol PC-bound palmitate [multiplied by] [h.sup.-1] [multiplied by] g wet [lung.sup.-1] (P [is less than] 0.05). We conclude that, whereas surfactant secretion was inhibited by glucose infusion, neither total surfactant PC synthesis nor the surfactant PC pool size was significantly affected due to an increased reliance on de novo synthesized fatty acids. phosphatidylcholine; isotope; synthesis; secretion