Long-Term Persistance of the Pathophysiologic Response to Severe Burn Injury

Main contributors to adverse outcomes in severely burned pediatric patients are profound and complex metabolic changes in response to the initial injury. It is currently unknown how long these conditions persist beyond the acute phase post-injury. The aim of the present study was to examine the persistence of abnormalities of various clinical parameters commonly utilized to assess the degree hypermetabolic and inflammatory alterations in severely burned children for up to three years post-burn to identify patient specific therapeutic needs and interventions. Nine-hundred seventy-seven severely burned pediatric patients with burns over 30% of the total body surface admitted to our institution between 1998 and 2008 were enrolled in this study and compared to a cohort non-burned, non-injured children. Demographics and clinical outcomes, hypermetabolism, body composition, organ function, inflammatory and acute phase responses were determined at admission and subsequent regular intervals for up to 36 months post-burn. Statistical analysis was performed using One-way ANOVA, Student's t-test with Bonferroni correction where appropriate with significance accepted at p<0.05. Resting energy expenditure, body composition, metabolic markers, cardiac and organ function clearly demonstrated that burn caused profound alterations for up to three years post-burn demonstrating marked and prolonged hypermetabolism, p<0.05. Along with increased hypermetabolism, significant elevation of cortisol, catecholamines, cytokines, and acute phase proteins indicate that burn patients are in a hyperinflammatory state for up to three years post-burn p<0.05. Severe burn injury leads to a much more profound and prolonged hypermetabolic and hyperinflammatory response than previously shown. Given the tremendous adverse events associated with the hypermetabolic and hyperinflamamtory responses, we now identified treatment needs for severely burned patients for a much more prolonged time

Bile acids suppress the secretion of very-low-density lipoprotein by human hepatocytes in primary culture

The existence of a relationship between bile acid and triacylglycerol metabolism in humans has been established, but the underlying mechanism and its physiological relevance have remained unclear, We have studied the effects of bile acids on the secretion of very-low-density lipoprotein (VLDL)-associated triacylglycerol, using [H-3]glycerol labeling technique, and apolipoprotein B (apoB) in human hepatocytes in primary culture. Human hepatocytes secrete nascent VLDL with an average diameter of about 40 nm, Lipid composition of the particles resembles that reported for plasma VLDL, with the exception of a markedly lower cholesterylester content. In 24-hour cultured human hepatocytes, physiological (i.e., portal) concentrations of taurocholic acid (10 to 200 mu mol/L) suppressed [H-3]triacylglycerol secretion dose dependently. The degree of inhibition highly correlated (r = .87, P <.01) with taurocholic acid content of the cells of different preparations (n = 7). ApoB secretion was inhibited by taurocholic acid to a similar extent as [H-3]triacylglycerol secretion (r = .93, P <.01). Lipid composition of secreted VL;DL particles did not change during taurocholic acid-induced suppression. No effects on intracellular apoB, [H-3]triacylglycerol, triacylglycerol, and cholesterol mass were observed, nor did taurocholic acid affect protein synthesis, albumin secretion, or lactate dehydrogenase (LDH) release. Cellular cholesteryl ester (CHE) mass, however, was markedly reduced. Our results show that bile acids strongly interfere with the assembly or secretion of VLDL particles by human hepatocytes, suggesting a physiological function of the enterohepatic circulation of bile acids in the regulation of postprandial serum lipid levels