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

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

Palynology of the glacial sediments associated with the End Ordovician Southern Polar ice sheet

editorial reviewe

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

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

Paleoecology and Phylogenetics of an Hirnantian Freshwater Palynological Assemblage from the Arabian Plate

peer reviewe

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

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

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Palaeoenvironmental interpretation of microphytoplankton diversity trends in the Cambrian-Ordovician of the northern Sahara Platform

Analysis of vertical fluctuations in assemblage diversity and relative abundances of microphytoplankton morphological classes permits palaeoenvironmental reconstructions of the Cambrian-Ordovician stratal sequences in the Hassi-R'Mel area (north-central Algeria) and northern Rhadames Basin (southern Tunisia). Abundance fluctuations of acritarch morphological classes and assemblage diversity appear to be related to changes in depositional facies. The present palaeoenvironmental interpretation is primarily based on a comparison with microphytoplankton distributional trends in modern depositional environments. Where possible, the observations are tested against palaeoenvironmental information derived independently from previous lithostratigraphical, macropalaeontological, and petrographical studies of the formations investigated. The present data support the following palaeoenvironmental scenario: during Late Cambrian times, relatively shallow water, neritic conditions prevailed throughout the study area, with evidence for a more proximal environment in southern Tunisia. In the early Tremadoc, open marine, offshore conditions characterized the central Algerian region, but a shallower water setting is indicated for southern Tunisia. During the late Arenig-Llanvirn interval, an open marine, offshore setting is envisaged for the southern Tunisian region, with more proximal conditions prevailing in the Algerian Hassi-R'Mel area. During the entire Ashgill, an essentially restricted marine environment was established throughout the study area. Some stratigraphically important acritarch species (e.g. Acanthodiacrodium angustum) appear to be facies-sensitive; the recognition of palaeoecological control on microphytoplankton distribution has important consequences on the biostratigraphic application of these microfossils. (C) 2000 Elsevier Science B.V. All rights reserved

Stratigraphic significance of acritarchs in Cambro-Ordovician boundary strata, Hassi-Rmel area, Algerian Sahara

Palynological investigation of 37 samples cored from boreholes Nl-2 and Uc-101 in Cambrian-Ordovician boundary beds of northwestern Algeria (Hassi-Rmel area) enables the definition of three, stratigraphically successive acritarch assemblages: HM/A, HM/B, and HM/C, tentatively referred here to the uppermost Cambrian, basal lower Tremadoc, and lower Tremadoc, respectively. The first assemblage has been found in the lower and middle parts of the arenaceous «Grès de Bordj Nili» unit and includes, inter alia, Cristallinium randomense, Dasydiacrodium obsonum, Ladogella rotundiformis, Timofeevia phosphoritica, Trunculumarium sp., and Veryhachium dumontii. Assemblage HM/B (upper third of the same stratigraphic unit) is characterized by: Acanthodiacrodium complanatum, A. sp. cf. A. angustum, Dasydiacrodium tumidum, Polygonium pungens, Stellifendium cortinulum, and S. furcatum, together with an increase in abundance and differentiation of Diacromorphitae and Herkomorphitae. The third assemblage, HM/C, is marked by the introduction of: Cymatiogalea cristata, C. membranispina, C. gorkae, Polygonium gracile, Stelliferidium stelligerum, S. simplex, and, in the upper part, Vulcanisphaera britannica and Acanthodiacrodium ubui. Chronostratigraphic attributions are based on comparison with previously established acritarch zones correlative with macrofossil zones. Occurrence of graptolites of the Rhabdinopora flabelliformis s.l. group in the «Argiles d'El Gassi» confirms an early Tremadoc age for that unit. The discordance in the composition of acritarch suites between assemblages HM/A and HM/B is tentatively proposed here as a palynologically easily detectable horizon approximating regionally to the Cambrian-Ordovician boundary. In the systematic section, 51 acritarch species are described and illustrated, including the following new species: Acanthodiacrodium baculatum, A. capillatum, Baltisphaeridium verutum, Cymatiogalea parva, and Stelliferidium velatum