Free serum cortisol during the postoperative acute phase response determined by equilibrium dialysis liquid chromatography-tandem mass spectrometry

In severely ill patients low concentrations of the corticosteroid binding globulin are typically found; the aim of this study was to quantify directly free bioactive cortisol concentrations in the sera of postoperative cardiosurgical patients. Serum samples of 12 consecutive patients undergoing aortocoronary bypass surgery taken preoperatively and on the postoperative days 1 to 4 were analyzed. Total serum cortisol was quantified using liquid chromatographytandem mass spectrometry with an online sample extraction system and trideuterated cortisol as the internal standard, and free serum cortisol was measured after overnight equilibrium dialysis. Whereas on the first postoperative day, the median total serum cortisol concentration was approximately twofold increased compared to preoperative samples (preoperatively, 245 nmol/l (interquartile range (IQR) 203293 nmol/l); first postoperative day, 512 nmol/l (IQR 410611 nmol/l)), median dialyzable free cortisol concentration was almost sevenfold increased (preoperatively, 14.2 nmol/l (IQR 10.920.7 nmol/l); first postoperative day, 98.3 nmol/l (IQR 81.3134 nmol/l)). On the fourth postoperative day, median free cortisol was still significantly increased compared to baseline sampling (p < 0.05), whereas median total cortisol was not. A median of 5.7% (IQR 5.47.0%) of total cortisol was found as free cortisol on the preoperative day, 21.2% (IQR 18.9 23.5%) on the first postoperative day and 10.5% (IQR 9.814.0%) on the fourth postoperative day. It is concluded that during the postoperative period the freeto bound ratio of cortisol is highly variable and that during the acute phase response direct quantification of free bioactive cortisol concentrations seems to be biologically more appropriate than the measurement of total cortisol concentrations

PGC-1α Inhibits Oleic Acid Induced Proliferation and Migration of Rat Vascular Smooth Muscle Cells

BACKGROUND: Oleic acid (OA) stimulates vascular smooth muscle cell (VSMC) proliferation and migration. The precise mechanism is still unclear. We sought to investigate the effects of peroxisome proliferator-activated receptor gamma (PPARgamma) coactivator-1 alpha (PGC-1alpha) on OA-induced VSMC proliferation and migration. PRINCIPAL FINDINGS: Oleate and palmitate, the most abundant monounsaturated fatty acid and saturated fatty acid in plasma, respectively, differently affect the mRNA and protein levels of PGC-1alpha in VSMCs. OA treatment resulted in a reduction of PGC-1alpha expression, which may be responsible for the increase in VSMC proliferation and migration caused by this fatty acid. In fact, overexpression of PGC-1alpha prevented OA-induced VSMC proliferation and migration while suppression of PGC-1alpha by siRNA enhanced the effects of OA. In contrast, palmitic acid (PA) treatment led to opposite effects. This saturated fatty acid induced PGC-1alpha expression and prevented OA-induced VSMC proliferation and migration. Mechanistic study demonstrated that the effects of PGC-1alpha on VSMC proliferation and migration result from its capacity to prevent ERK phosphorylation. CONCLUSIONS: OA and PA regulate PGC-1alpha expression in VSMCs differentially. OA stimulates VSMC proliferation and migration via suppression of PGC-1alpha expression while PA reverses the effects of OA by inducing PGC-1alpha expression. Upregulation of PGC-1alpha in VSMCs provides a potential novel strategy in preventing atherosclerosis