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

Prothrombotic mutations, family history and the risk of thrombosis in postmenopausal women: implications for hormone replacement therapy

Objective Hormone replacement therapy (HRT) is acknowledged as the gold standard for the alleviation of climacteric vasomotor symptoms. Prothrombotic genetic variants have been suggested to increase thrombotic risk among HRT users. The aim of the study was to determine whether a positive family history may identify a genetic predisposition for thrombosis in women before prescribing HRT. Methods From January 2005 to May 2009, we consecutively enrolled 145 asymptomatic women (mean age 51.2+5.4 years) without previous episodes of venous and/or arterial thrombosis referred to our Genetics Research Unit before starting HRT. A detailed family history was reconstructed and we identified 48 women (33.1%) with a positive family history, defined as venous thromboembolism and/or stroke or heart attack, in first-degree relatives before 60 years for men and 65 years for women. A group of 121 women (mean age 54.0+9.1 years) with an episode of venous and/or arterial thrombosis was also included. Genetic screening for factor V Leiden, prothrombin G20210A and methylenetetrahydrofolate reductase C677T polymorphisms was performed. Results The frequency of factor V Leiden or prothrombin G20210A mutations was significantly higher both in asymptomatic women with a positive family history (16.7% vs. 2.1%, p?0.001) and in patients with thrombosis (12.4% vs. 2.1%; p?0.005) compared with asymptomatic women without a family history. Multivariate regression analysis showed a synergic effect between the presence of one prothrombotic mutation and family history on the risk of thrombosis (odds ratio 3.7, 95% confidence interval 1.9-7.2). Conclusions A positive family history of thrombosis is a sensitive indicator for selected genetic testing in high-risk women before starting HRT

Hormone replacement therapy and cardioprotection. A new dawn? A statement of the \u27Gruppo di studio sulle malattie cardiovascolari nella donna\u27 of the societ? italiana di cardiologia on hormone replacement therapy in postmenopausal women

Cardiovascular disease is the leading cause of death in women in western countries. Despite preventive strategies, in the past decades, the incidence of cardiovascular events has shown a decline in men but a rise in women, matching the growth of the population of postmenopausal women. Several epidemiological findings suggest the causative pathophysiological role of ovarian hormone deficiency in the development of cardiovascular disease in women. Observational and randomized studies have suggested that hormone replacement therapy in early postmenopause could be beneficial from a cardiovascular point of view. Conversely, aging, time since menopause and presence of cardiovascular risk factors or cardiovascular disease may decrease its efficacy and increase the risk of cardiovascular events. It is plausible that the unfavorable effects of the estrogen/progestin combination used in the randomized studies are not related to the hormone preparation per se but rather to the use of hormones in the less receptive group of women, older and with cardiovascular risk factors. Clinical judgment, choice of the right dose and estrogen/ progestin combination are of pivotal importance to maximize the beneficial effect of estrogen replacement therapy/hormone replacement therapy, especially if given within a reasonable time after the menopause to the women who need the therapy for the relief of menopausal symptoms

HIV infection and frequency of micronucleus in human peripheral blood cells

Purpose. People living with HIV have higher rates of malignancies than the general population in the era of active antiretroviral therapy (ART). Genotoxic effects of HIV infection and/or ART that can induce neoplastic development are not yet well known. A prospective cohort study to investigate DNA damage measured through the micronuclei (MN) frequency in HIV-patients has been performed. Methods. Peripheral blood mononuclear cells (PBMC) were isolated from 52 HIV-patients treated with ART and 55 healthy controls. Results. By the comparison of MN frequency, a significant difference between HIV-patients (15.5 ± 9.8) and controls (6.0 ± 3.6) (p < 0.001) has been revealed. In univariate linear regression analysis, HCV infection (r = 0.31; p < 0.001), HIV-RNA (r = 0.29; p < 0.03) and duration of infection (r = - 0.16; p < 0.25) were associated with MN frequency; while only viral load (VL) significantly correlates (r = 0.29; p < 0.05) in a multiple regression model. Conclusions. The association of VL with MN frequency supports a genotoxic effect of HIV infection

Ferulated Poly(vinyl alcohol) based hydrogels

New graft copolymers were prepared by reaction of poly (vinyl alcohol) (PVA) with mono-imidazolide or bis-imidazolide derivatives of ferulic acid (FA) with the formation of ester bonds. The obtained graft copolymers, thanks to the crosslinking capability of FA, formed in water strong gels as verified by rheological analyses. The resulting hydrogels were characterized to evaluate their applicability as wound dressing. In this perspective, their capability to absorb and retain a large amount of fluid without dissolving was verified by swelling kinetics and Moisture Vapour Transmission Rate measurements. Their stability towards mechanical solicitations was assessed by quantifying elasticity, compliance, stress-relaxation, and adhesivity properties. The analyses pointed out that hydrogel PVA-FA2-3 obtained by feruloylation of PVA with bis-imidazole derivative of ferulic acid using an acylation agent/polymer molar ratio 0.03/1 resulted the best candidate for the foreseen application

Cytoplasmic cleavage of IMPA1 3' UTR is necessary for maintaining axon integrity

The 3′ untranslated regions (3′ UTRs) of messenger RNAs (mRNAs) are non-coding sequences involved in many aspects of mRNA metabolism, including intracellular localization and translation. Incorrect processing and delivery of mRNA cause severe developmental defects and have been implicated in many neurological disorders. Here, we use deep sequencing to show that in sympathetic neuron axons, the 3′ UTRs of many transcripts undergo cleavage, generating isoforms that express the coding sequence with a short 3′ UTR and stable 3′ UTR-derived fragments of unknown function. Cleavage of the long 3′ UTR of Inositol Monophosphatase 1 (IMPA1) mediated by a protein complex containing the endonuclease argonaute 2 (Ago2) generates a translatable isoform that is necessary for maintaining the integrity of sympathetic neuron axons. Thus, our study provides a mechanism of mRNA metabolism that simultaneously regulates local protein synthesis and generates an additional class of 3′ UTR-derived RNAs