ABSTRACT

We applied a combined proteomic and metabolomic approach to obtain novel mechanistic insights in PKCε-mediated cardioprotection. Mitochondrial and cytosolic proteins from control and transgenic hearts with constitutively active or dominant negative PKCε were analyzed using difference in-gel electrophoresis (DIGE). Among the differentially expressed proteins were creatine kinase, pyruvate kinase, lactate dehydrogenase, and the cytosolic isoforms of aspartate amino transferase and malate dehydrogenase, the two enzymatic components of the malate aspartate shuttle, which is required for the import of reducing equivalents from glycolysis across the inner mitochondrial membrane. These enzymatic changes appeared to be dependent on PKCε activity, as they were not observed in mice expressing inactive PKCε. High-resolution proton nuclear magnetic resonance (1H-NMR) spectroscopy confirmed a pronounced effect of PKCε activity on cardiac glucose and energy metabolism: normoxic hearts with constitutively active PKCε had significantly lower concentrations of glucose, lactate, glutamine and creatine, but higher levels of choline, glutamate and total adenosine nucleotides. Moreover, the depletion of cardiac energy metabolites was slower during ischemia/reperfusion injury and glucose metabolism recovered faster upon reperfusion in transgenic hearts with active PKCε. Notably, inhibition of PKCε resulted in compensatory phosphorylation and mitochondrial translocation of PKCδ. Taken together, our findings are the first evidence that PKCε activity modulates cardiac glucose metabolism and provide a possible explanation for the synergistic effect of PKCδ and PKCε in cardioprotection.

ObjectiveThe aim of this study was to evaluate indications, efficacy, and complications associated with pelvic arterial embolization (PAE) for postpartum hemorrhage (PPH).MethodsWe retrospectively reviewed the medical records of 117 consecutive patients who underwent PAE for PPH between January 2006 and June 2013.ResultsIn our single-center study, 117 women underwent PAE to control PPH refractory to conservative management including uterine massage, use of uterotonic agents, surgical repair of genital tract lacerations, and removal of retained placental tissues. Among 117 patients, 69 had a vaginal delivery and 48 had a Cesarean section. The major indication for embolization was uterine atony (54.7%). Other causes were low genital tract lacerations (21.4%) and abnormal placentation (14.5%). The procedure showed a clinical success rate of 88.0% with 14 cases of PAE failure; there were 4 hemostatic hysterectomies and 10 re-embolizations. On univariate analysis, PAE failure was associated with overt disseminated intravascular coagulation (P=0.009), transfusion of more than 10 red blood cell units (RBCUs, P=0.002) and embolization of both uterine and ovarian arteries (P=0.003). Multivariate analysis showed that PAE failure was only associated with transfusions of more than 10 RBCUs (odds ratio, 8.011; 95% confidence interval, 1.531-41.912; P=0.014) and embolization of both uterine and ovarian arteries (odds ratio, 20.472; 95% confidence interval, 2.715-154.365; P=0.003), which were not predictive factors, but rather, were the results of longer time for PAE. Three patients showed uterine necrosis and underwent hysterectomy.ConclusionPAE showed high success rates, mostly without procedure-related complications. Thus, it is a safe and effective adjunct or alternative to hemostatic hysterectomy, when primary management fails to control PPH.

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Pregnancies with one elevated glucose tolerance test value after 1 h exhibited increased adverse maternal and perinatal outcomes compared with the group with all normal OGTT values or the groups with an elevated glucose tolerance test value after 2 or 3 h.