1,720,962 research outputs found

    L-Carnitine attenuates fibrosis and inflammation in C57BL/6 mice with dietary-induced steatohepatitis

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    Nonalcoholic steatohepatitis (NASH) represents an advanced stage of fatty liver disease developed in the absence of alcohol abuse and its prevalence is increasing in western countries in parallel with Type 2 Diabetes and metabolic syndrome incidence. NASH is a strong marker of cardiovascular risk and in the last few decades it has become evident that there is a mutual interaction between heart and liver influencing their individual functions. In effect, NASH characterized by excess of intracellular fatty acids, severe inflammatory and fibrotic state, plays a critical role in two principal tissues: liver and heart. Several studies have examined the effectiveness of L-Carnitine (LC) in liver function and have recognized LC as a nutritional supplementation in cardiovascular disease. The present study was designed to investigate the effects of LC administration on liver and heart function and morphology in mice models of steatohepatitis, induced by a methionine-choline deficient diet (MCD). C57BL/6 mice male (n=18, age:12 weeks) were divided in 3 different groups: control group (CONTR) were fed for 6 weeks with a normal diet while both MCD and LC groups received MCD diet. From the 4th week LC group received MCD diet enriched with 200mg/kg/die LC (drinking water). The results showed that there are no significant differences in body weight between MCD and LC mice groups, while, as expected, there is a significant weight loss in MCD and LC groups in respect with CONTR. Furthermore, insulin sensitivity (IPGTT test) and GLUT4 protein content showed no differences between groups. Tissues fat deposition, inflammatory infiltration and fibrosis were, then, investigated. Different histopathology staining methods showed that LC significantly reduces fat accumulation. Immunofluorescence assay revealed an important downregulation of the two markers of tissue fibrosis: alpha smooth muscle actin protein level and Kruppel-like factor (KLF15). To clarify LC cellular mechanisms in counteracting inflammatory liver state, we evaluated NFκB pathway and PPARγ: our results indicated that NFkB increase, caused by MCD diet, was markedly attenuated by LC. In addition, LC significantly stimulates Ca2+/calmodulin-dependent kinases II activity, suggesting that LC could ameliorate mitochondrial function. Noteworthy, we observed LC actives ERKs pathway, which is correlated with a reduction of oxidative stress and hepatotoxicity. In parallel, to investigate LC anti-inflammatory and fibrotic role in heart, we studied STAT-3 activation: LC significantly decreases STAT 3 activation observed in MCD heart. This data is in accordance with the reduction of Calcium signaling in LC heart compared to MCD. In conclusion, LC appear to exert different beneficial actions on the liver-heart axis counteracting steatohepa¬titis. LC supplementation may be used in order to prevent disease progression in these analyzed tissues, inhibiting the inflammation and fibrotic pathways

    Effects of hazelnuts and cocoa on vascular reactivity in healthy subjects: a randomised study

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    Cocoa helps maintain endothelium-dependent vasodilation; consumption of hazelnuts has been associated with reduced cardiovascular disease risk. This study assesses the effects of hazelnuts and cocoa on vascular reactivity and metabolic profile. Sixty-one healthy volunteers, examined in a randomised, controlled, two-week intervention, received one of six breakfast integrations containing either hazelnuts, cocoa, both or none. Consumption of unpeeled hazelnuts improved HDL-cholesterol (+7.3%, p = .01 vs. baseline, p = .02 vs. control). Brachial artery peak systolic velocities (PSV) at rest increased with hazelnut integrations by 43.4% (p = .04 vs. control) and hazelnut-cocoa integrations by 26.4% (p = .01 vs. control). PSV after 3-min cuff occlusion increased by 60.7% (p = .002 vs. control) with a peeled hazelnut snack and by 64.7% with a hazelnut-cocoa integration (p = .04 vs. control). The combination hazelnut-cocoa may act in a synergic and protective way on cardiovascular system

    Proteome analysis to study the effects of lupin gamma-conglutin on cellular metabolism in cultured C2C12 and HepG2 cells

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    gamma-Conglutin is a tetrameric glycoprotein representing about 5% of lupin seed proteins. Each monomer is made up of two disulphide-linked subunits of 17 and 29 kDa (1). The protein was found to decrease glycaemia in glucose overload trials carried out on animal models and healthy human subjects (2, 3). The translocation of the intact protein through the intestinal barrier in in vitro and ex vivo experiments has been demonstrated (4). -Conglutin showed insulin-mimetic activity and was able to increase glucose consumption by myocites and HepG2 cells (5, 6). This experimental set of data leads to consider -conglutin as a possible nutraceutical molecule for the prevention of diabetes II-related diseases. In order to contribute to unveiling the molecular mechanisms at the basis of its effects on cell metabolism, two different cell lines, namely myoblastic C2C12 and HepG2, were incubated with -conglutin for 4 and 6 hours, respectively. After accurate cell washing, the proteomes were analyzed by 2D electrophoresis, Western blot and in-gel fluorescence stain (Phos Tag) for phosphoprotein detection. The results showed that the protein was able to enter the cells, where it was detected in intact form. No polypeptides with Mr lower than those of the full size subunits were evidenced. Interestingly, a polypeptide of 29 kDa subunit reacting with specific -conglutin antibodies, but not with Phos Tag dye, appeared with a different pI in HepG2 cells. The nature of such modifications and possible changes in the phosphorylation pattern of the cells are still under investigation. (1) Magni et al (2007) Phytochem 68(7), 997. (2) Magni et al (2004) J Nutr Biochem 15, 646. (3) Bertoglio et al (2011) Fitoterapia 82(7), 933. (4) Capraro et al (2011) Food Chem 125, 1279. (5) Terruzzi et al (2011) Nutr Metab Cardiovasc Dis 21(3), 197. (6) Lovati et al (2012) Br J Nutr, 107(1), 67

    Iperuricemia e disfunzione sessuale maschile

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    L’iperuricemia è una condizione definita dalla presenza di livelli circolanti di acido urico superiori a 7,0 mg/dl. All’iperuricemia si associano di frequente disfunzione endoteliale e stress ossidativo con aumento di rischio cardiovascolare e disfunzione erettile. Dati della letteratura infatti suggeriscono che l’iperuricemia determina un aumento del rischio di disfunzione erettile. La conferma di tale possibile associazione potrà suggerire la prescrizione di una terapia combinata con farmaci volti a ridurre l’acido urico in eccesso insieme a inibitori della fosfodiesterasi di tipo 5 per contrastare validamente la disfunzione erettile nei soggetti con iperuricemia

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Genetic polymorphisms of the enzymes involved in DNA methylation ans synthesis in elite atletes

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    Physical exercise induces adaptive changes leading to a muscle phenotype with an enhanced performance. We first investigated whether genetic polymorphisms altering enzymes involved in DNA methylation, probably responsible of DNA methylation deficiency, are present in athletes DNA. We determined the polymorphic variants C667T/A1298C of 5,10-methylenetetrahydrofolate reductase (MTHFR), A2756G of methionine synthase (MTR), A66G of methionine synthase reductase (MTRR), G742A of betaine:homocysteine methyltransferase (BHMT) and 68-bp ins of cystathionine β-synthase (CBS) genes in 77 athletes and 54 control subjects. The frequency of MTHFR (AC), MTR (AG) and MTRR (AG) heterozygous genotypes was found statistically different in the athletes compared to the control group (p=0.0001; p=0.018 and p=0.0001) suggesting a reduced DNA methylating capacity. We then therefore assessed whether assessed whether DNA hypomethylation might increase the expression of myogenic proteins expressed during early (Myf-5 and MyoD), intermediate (Myf-6) and late phase (MHC) of myogenesis, in a cellular model of hypomethylated or un-hypomethylated C2C12 myoblasts. Myogenic proteins are largely induced in hypomethylated cells (F.C.=Myf-5:1.21, 1.35; MyoD:0.9, 1.47; Myf-6:1.39, 1.66; MHC:1.35, 3.10 in GMA, DMA respectively) compared with the control groups (F.C.=Myf-5:1.0, 1.38; MyoD:1.0, 1.14; Myf-6:1.0, 1.44; MHC:1.0, 2.20 in GM, DM respectively). Diameters and length of hypomethylated myotubes were greater then their respective controls. Our findings suggest that DNA hypomethylation due to lesser efficiency of polymorphic MTHFR, MS and MSR enzymes, induces the activation of factors determining proliferation and differentiation of myoblasts promoting muscle growth and increase of muscle mass

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods
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