1,720,985 research outputs found

    The protective effect of moderate hypothermia during intestinal ischemia-reperfusion is associated with modification of hepatic transcription factor activation

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    Background/purpose: Moderate hypothermia throughout intestinal ischemia-reperfusion (IIR) injury reduces multiple organ dysfunction. Heat shock proteins (HSPs) have been shown to be protective against ischemia-reperfusion injury, and STAT (Signal Transducers and Activators of Transcription) proteins are pivotal determinants of the cellular response to reperfusion injury. The aim of this study is to investigate the mechanism of hypothermic protection during IIR.Methods: Adult rats underwent intestinal ischemia-reperfusion (IIR), 60-minute ischemia and 60-minute reperfusion, or sham (120 minutes) at either normothermia or moderate hypothermia. Four groups of animals were studied: (1) normothermic sham (NS), (2) normothermic IIR (NIIR), (3) hypothermic sham (HS), and (4) hypothermic IIR (HIIR). Western blotting measured heat shock protein expression, phosphorylated (p-) and total (T-) hepatic STAT-1 and STAT-3.Results: There were no differences in expression of HSPs 27, 47, 60, i70, c70, or 90 between any of the experimental groups. NIIR caused a significant increase in p-STAT-1 compared with normothermic sham (P < .05) and a highly significant increase in p-STAT-3 (P < .001), both these increases were completely abolished by moderate hypothermia (P < .01 v NIIR.)Conclusions: The protective effect of moderate hypothermia on liver is not mediated by HSP expression at this time-point. Hypothermia may act by decreasing hepatic STAT activation, supporting the potential therapeutic role of moderate hypothermia. Modulation of STAT activation may also provide novel therapeutic targets

    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

    Urocortin protects cardiac myocytes from ischemia/reperfusion injury by attenuating calcium-insensitive phospholipase A2 gene expression

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    We have used Affymetrix gene chip technology to look for changes in gene expression caused by a 24 h exposure of rat primary neonatal cardiac myocytes to the cardioprotective agent urocortin. We observed a 2.5-fold down-regulation at both the mRNA and protein levels of a specific calcium-insensitive phospholipase A2 enzyme. Levels of lysophosphatidylcholine, a toxic metabolite of phospholipase A2, were lowered by 30% in myocytes treated with urocortin for 24 h and by 50% with the irreversible iPLA2 inhibitor bromoenol lactone compared with controls. Both 4 h ischemia and ischemia followed by 24 h reperfusion caused a significant increase in lysophosphatidylcholine concentration compared with controls. When these myocytes were pretreated with urocortin, the ischemia-induced increase in lysophosphatidylcholine concentration was significantly lowered. Moreover, co-incubation of cardiac myocytes with urocortin, or the specific phospholipase A2 inhibitor bromoenol lactone, reduces the cytotoxicity produced by lysophosphatidylcholine or ischemia/reperfusion. Similarly, in the intact heart ex vivo we found that cardiac damage measured by infarct size was significantly increased when lysophoshatidylcholine was applied during ischemia, compared with ischemia alone, and that pre-treatment with both urocortin and bromoenol lactone reversed the increase in infarct size. This, to our knowledge, is the first study linking the cardioprotective effect of urocortin to a decrease in a specific enzyme protein and a subsequent decrease in the concentration of its cardiotoxic metabolite

    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

    Gene therapy using herpes simplex virus-based vectors

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    Gene therapy involves the use of specific genes to treat human diseases and is thus critically dependent on efficient gene delivery systems. Although a variety of systems for such gene delivery are under development, HSV has unique advantages in terms of its large genome size and for gene delivery in the nervous system because of its ability to enter a latent state in neuronal cells. Considerable progress has been made in the effective disablement of this virus whilst retaining its ability to deliver genes and in producing long term expression of the foreign gene. Although much remains to be achieved in the further disablement of the virus and its testing in rodent and primate models of human diseases, it is likely that these viruses may ultimately be of use in human gene therapy procedures particularly for otherwise intractable neurological diseases

    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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