62 research outputs found

    Meta-Analysis of the Association between Transforming Growth Factor-Beta Polymorphisms and Complications of Coronary Heart Disease

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    Objective: To investigate the association between common transforming growth factor beta (TGF-β) single nucleotide polymorphisms (SNP) and significant complications of coronary heart disease (CHD).\ud \ud Method: We performed a meta-analysis of published case-control studies assessing the association of TGF-β SNPs with a range of CHD complications. A random effects model was used to calculate odds ratios and confidence intervals. Analyses were conducted for additive, dominant and recessive modes of inheritance.\ud \ud Results: Six studies involving 5535 cases and 2970 controls examining the association of common SNPs in TGF-β1 with CHD were identified. Applying a dominant model of inheritance, three TGF-β1 SNPs were significantly associated with CHD complications: The T alleles of rs1800469 (OR = 1.125, 95% CI 1.016–1.247, p = 0.031) and rs1800470 (OR = 1.146, 95% CI 1.026–1.279, p = 0.021); and the C allele of rs1800471 (OR = 1.207, 95% CI 1.037–1.406, p = 0.021).\ud \ud Conclusion: This meta-analysis suggests that common genetic polymorphisms in TGF-β1 are associated with complications of CHD

    Renin-angiotensin-aldosterone system polymorphisms: a role or a hole in occurrence and long-term prognosis of acute myocardial infarction at young age

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    <p>Abstract</p> <p>Background</p> <p>The renin-angiotensin-aldosterone system (RAAS) is involved in the cardiovascular homeostasis as shown by previous studies reporting a positive association between specific RAAS genotypes and an increased risk of myocardial infarction. Anyhow the prognostic role in a long-term follow-up has not been yet investigated.</p> <p>Aim of the study was to evaluate the influence of the most studied RAAS genetic Single Nucleotide Polymorphisms (SNPs) on the occurrence and the long-term prognosis of acute myocardial infarction (AMI) at young age in an Italian population.</p> <p>Methods</p> <p>The study population consisted of 201 patients and 201 controls, matched for age and sex (mean age 40 ± 4 years; 90.5% males). The most frequent conventional risk factors were smoke (p < 0.001), family history for coronary artery diseases (p < 0.001), hypercholesterolemia (p = 0.001) and hypertension (p = 0.002). The tested genetic polymorphisms were angiotensin converting enzyme insertion/deletion (ACE I/D), angiotensin II type 1 receptor (AGTR1) A1166C and aldosterone synthase (CYP11B2) C-344T. Considering a long-term follow-up (9 ± 4 years) we compared genetic polymorphisms of patients with and without events (cardiac death, myocardial infarction, revascularization procedures).</p> <p>Results</p> <p>We found a borderline significant association of occurrence of AMI with the ACE D/I polymorphism (DD genotype, 42% in cases vs 31% in controls; p = 0.056). DD genotype remained statistically involved in the incidence of AMI also after adjustment for clinical confounders.</p> <p>On the other hand, during the 9-year follow-up (65 events, including 13 deaths) we found a role concerning the AGTR1: the AC heterozygous resulted more represented in the event group (p = 0.016) even if not independent from clinical confounders. Anyhow the Kaplan-Meier event free curves seem to confirm the unfavourable role of this polymorphism.</p> <p>Conclusion</p> <p>Polymorphisms in RAAS genes can be important in the onset of a first AMI in young patients (ACE, CYP11B2 polymorphisms), but not in the disease progression after a long follow-up period. Larger collaborative studies are needed to confirm these results.</p

    Ebselen : an antimalarial compound active against ferredoxin-NADP+ reductase of Plasmodium falciparum

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    Ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one)is a seleno-organic compound that has been extensively studied as an anti-inflammatory drug. It reacts with thiol groups forming selenylsulphide bonds and it has been reported to inhibit a variety of enzymes involved in different processes1. Moreover, ebselen has been shown possesse an antimalarial activity in vitro against P. falciparum strains in the asexual stages. Since this compounds displayed no cytotoxic effects on human epatocyte, it is of interest for the design of antimalarial drugs2. The effect of ebselen on ferredoxin-NADP+ reductase of Plasmodium falciparum (PfFNR), an enzyme located in the apicoplast of the parasite3, has been investigated. Ebselen was found to slowly and irreversibly inhibit PfFNR targeting one or more Cys residue of the enzyme. Spectrofluorimetric studies pointed out that ebselen promotes the release of prosthetic group FAD. PfFNR was found to be particularly sensitive to inactivation in comparison to similanr flavoenzymes. The compound is 9-fold less active against the omologue FNR from spinach leaf, while Mycobacterium tuberculosis FprA, a ferredoxin-reductase structurally unrelated to plant type FNRs, turned out to be completely insensitive to this inhibitor, These preliminary data suggest that PfFNR could be a potential target of the antiplasmodial activity of ebselen.1. Schewe T. (1995) Gen. Pharmac. 26 (6): 1153-1169 2. Huter A. M. et al. (1989) Parasitol Res. 75 (5): 353-60 3. Seeber F. et al. (2005) Curr. Pharm. Des. 11, 3159-317

    Expression of Plasmodium falciparum ferredoxin-NADP+ reductase in Escherichia coli as a cleavable fusion with the SUMO protein

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    The ferredoxin-NADP+ reductase of Plasmodium falciparum (PfFNR) is an enzyme similar to that found in non-photosynthetic plastids of plants (1). It is involved in the biosynthesis of isoprenoid precursors (2) and it has been proposed as a target for novel antimalarial drugs (3). In order to support in-depth inhibition studies, large amounts of recombinant PfFNR are required. To this aim, we have developed an E. coli expression system based on the fusion with the yeast SUMO protein (pET SUMO system, Invitrogen). Recombinant PfFNR has been purified by two successive steps of immobilized nickel ion affinity chromatography. Mature PfFNR has been generated during the purification procedure by treatment with recombinant SUMO protease. Although the total yield of the procedure is lowered by the tendency of the fusion product to undergo spontaneous splitting in vivo, this quick and cheap isolation protocol can provide about 30 mg highly purified PfFNR from each run. 1. Balconi, E., et al. (2009) FEBS J. 276, 3825\u20133836 2. R\uf6hrich, R.C., et al. (2005) FEBS Lett. 579, 6433\u20136438 3. Seeber, F., et al. (2005) Curr. Pharm. Des. 11, 3159\u20133172

    Polymer-Brush Lubrication in Oil: Sliding Beyond the Stribeck Curve

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    ISSN:1023-8883ISSN:1573-271
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