118 research outputs found

    T-786→C polymorphism of the endothelial nitric oxide synthase gene is associated with insulin resistance in patients with ischemic or non ischemic cardiomyopathy

    Get PDF
    Background: Insulin resistance (IR) and endothelial dysfunction are frequently associated in cardiac disease. The T-786→C variant in the promoter region of the endothelial nitric oxide synthase (eNOS) gene has been associated with IR in both non-diabetic and diabetic subjects. Aim of the study was to assess the reciprocal relationships between T-786→C eNOS polymorphism and IR in ischemic and non-ischemic cardiomyopathy.Method: A group of 132 patients (108 males, median age 65 years) with global left ventricular (LV) dysfunction secondary to ischemic or non-ischemic heart disease was enrolled. Genotyping of T-786→C eNOS gene promoter, fasting glucose, insulin, and insulin resistance (defined as HOMA-IR index > 2.5) were determined in all patients.Results: Genotyping analysis yielded 37 patients homozygous for the T allele (TT), 70 heterozygotes (TC) and 25 homozygous for C (CC). Patients with CC genotype had significantly higher systemic arterial pressure, blood glucose, plasma insulin and HOMA index levels than TT. At multivariate logistic analysis, the history of hypertension and the genotype were the only predictors of IR. In particular, CC genotype increased the risk of IR (CI% 1.4-15.0, p < 0.01) 4.5-fold. The only parameter independently associated with the extent of LV dysfunction and the presence of heart failure (HF) was the HOMA index (2.4 CI% 1.1-5.6, p < 0.04).Conclusions: T-786→C eNOS polymorphism was the major independent determinant of IR in a population of patients with ischemic and non-ischemic cardiomyopathy. The results suggest that a condition of primitive eNOS lower expression can predispose to an impairment of glucose homeostasis, which in turn is able to affect the severity of heart disease. © 2012 Vecoli et al.; licensee BioMed Central Ltd

    A kinetic study of gamma-glutamyltransferase (GGT)-mediated S-nitrosoglutathione catabolism.

    Get PDF
    S-Nitrosoglutathione (GSNO) is a nitric oxide (NO) donor compound which has been postulated to be involved in transport of NO in vivo. It is known that c-glutamyl transpeptidase (GGT) is one of the enzymes involved in the enzyme-mediated decomposition of GSNO, but no kinetics studies of the reaction GSNO-GGT are reported in literature. In this study we directly investigated the kinetics of GGT with respect to GSNO as a substrate and glycyl- glycine (GG) as acceptor co-substrate by spectrophotometry at 334 nm. GGT hydrolyses the c-glutamyl moiety of GSNO to give S-nitroso-cysteinylglycine (CGNO) and c-glutamyl-GG. However, as both the substrate GSNO and the first product CGNO absorb at 334 nm, we optimized an ancillary reaction coupled to the enzymatic reaction, based on the copper-mediated decomposition of CGNO yielding oxidized cysteinyl-glycine and NO. The ancillary reaction allowed us to study directly the GSNO/GGT kinetics by following the decrease of the characteristic absorbance of nitrosothiols at 334 nm. A Km of GGT for GSNO of 0.398 ± 31 mM was thus found, comparable with Km values reported for other c-glutamyl substrates of GGT

    Impaired myocardial metabolic reserve and substrate selection flexibility during stress in patients with idiopathic dilated cardiomyopathy.

    Get PDF
    Under resting conditions, the failing heart shifts fuel use toward greater glucose and lower free fatty acid (FFA) oxidation. We hypothesized that chronic metabolic abnormalities in patients with dilated cardiomyopathy (DCM) are associated with the absence of the normal increase in myocardial glucose uptake and maintenance of cardiac mechanical efficiency in response to pacing stress. In 10 DCM patients and 6 control subjects, we measured coronary flow by intravascular ultrasonometry and sampled arterial and coronary sinus blood. Myocardial metabolism was determined at baseline, during atrial pacing at 130 beats/min, and at 15 min of recovery by infusion of [(3)H]oleate and [(13)C]lactate and measurement of transmyocardial arteriovenous differences of oxygen and metabolites. At baseline, DCM patients showed depressed coronary flow, reduced uptake and oxidation of FFA, and preferential utilization of carbohydrates. During pacing, glucose uptake increased by 106% in control subjects but did not change from baseline in DCM patients. Lactate release increased by 122% in DCM patients but not in control subjects. Cardiac mechanical efficiency in DCM patients was not different compared with control subjects at baseline but was 34% lower during stress. Fatty acid uptake and oxidation did not change with pacing in either group. Our results show that in DCM there is preferential utilization of carbohydrates, which is associated with reduced flow and oxygen consumption at rest and an impaired ability to increase glucose uptake during stress. These metabolic abnormalities might contribute to progressive cardiac deterioration and represent a target for therapeutic strategies aimed at modulating cardiac substrate utilization

    Morphology and wall ultrastructure of the megaspore Lagenicula (Triletes) mixta (Winslow 1962) comb. nov from the Carboniferous (Early Mississippian: mid Tournaisian) of Ohio, USA

    No full text
    Megaspores assigned to Lagenicula (Triletes) mixta (Winslow, M., 1962. Plant Spores and Other Microfossils from Upper Devonian and Lower Mississippian Rocks of Ohio. Geol. Surv., Prof. Paper 364,1-93.) comb. nov.. from the Carboniferous (Early Mississippian: mid Tournaisian) of northeastern Ohio, USA, have been analysed using light microscopy (LM), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). These studies provide new information on morphology, gross structure and wall ultrastructure. This taxon has a confused taxonomic history, and the new morphological information allows recognition as a distinct species that can be placed with the genus Lagenicula as a new combination. Morphological/ultrastructural studies confirm the lycopsid affinities of this megaspore and it is suggested that it probably derived from an arborescent lycopsid that belonged with the Lepidocarpaceae. Thus it is an early example of a megaspore derived from an arborescent lycopsid of the type that went on to dominate the Euramerican Coal Measure forests. The Ohio Tournaisian megaspore assemblage is surprisingly diverse revealing an interesting insight into vegetation ecology at this poorly understood time in plant history. (C) 2008 Elsevier B.V. All rights reserved
    • …
    corecore