659 research outputs found

    Pentoxifylline Plus Prednisolone versus Pentoxifylline Only for Severe Alcoholic Hepatitis: A Randomized Controlled Clinical Trial

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    Background: Prednisolone and pentoxifylline (PTX) have been shown to be individually useful in severe alcoholic hepatitis with Maddrey discriminant function (MDF) score .32. Previous report suggests that PTX is probably superior to prednisolone alone. However the efficacy of PTX and prednisolone combination over PTX alone in the management of acute alcoholic hepatitis (MDF score ≥32) is yet unrevealed.Aim: The present study was initiated to find out the efficacy of combined pentoxifylline and prednisolone versus PTX alone in acute alcoholic  hepatitis in respect of short and intermediate term outcomes.Subjects and Methods: A total of 124 patients with severe alcoholic hepatitis (MDF score ≥32) initially were evaluated. 62 patients who fulfilled the inclusion and exclusion criteria were randomized and divided into 2 groups. Group 1 received PTX only, whereas Group 2 received PTX plus Prednisolone. The total duration of follow-up was 12 months. Studentfs t-test, Chi-square test, the Kaplan-Meier methods were used forstatistical analysis. Results: A total of 60 patients, 30 in each group were available for finalanalysis. In Group-1, 6 patients expired at the end of 1 year (5 within 3 months and another after 3 months). In Group 2, 10 patients expired at the end of 1 year (9 within 3 months and another after 3 months). Though survival probability is higher among Group 1 patients but the difference is not statistically significant.Conclusion: The combination of PTX plus Prednisolone yields no additional benefit in terms of mortality and morbidity from that of PTX monotherapy.Keywords: Alcoholic hepatitis, Maddrey discriminant function score,  Pentoxifylline, Prednisolon

    Factors associated with infant mortality in Nepal: a comparative analysis of Nepal demographic and health surveys (NDHS) 2006 and 2011

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    Background: Infant mortality is one of the priority public health issues in developing countries like Nepal. The infant mortality rate (IMR) was 48 and 46 per 1000 live births for the year 2006 and 2011, respectively, a slight reduction during the 5 years’ period. A comprehensive analysis that has identified and compared key factors associated with infant mortality is limited in Nepal, and, therefore, this study aims to fill the gap. Methods: Datasets from Nepal Demographic and Health Surveys (NDHS) 2006 and 2011 were used to identify and compare the major factors associated with infant mortality. Both surveys used multistage stratified cluster sampling techniques. A total of 8707 and 10,826 households were interviewed in 2006 and 2011, with more than 99% response rate in both studies. The survival information of singleton live-born infants born 5 years preceding the two surveys were extracted from the ‘childbirth’ dataset. Multiple logistic regression analysis using a hierarchical modelling approach with the backward elimination method was conducted. Complex Samples Analysis was used to adjust for unequal selection probability due to the multistage stratified cluster-sampling procedure used in both NDHS.Results: Based on NDHS 2006, ecological region, succeeding birth interval, breastfeeding status and type of delivery assistance were found to be significant predictors of infant mortality. Infants born in hilly region (AOR = 0.43, p = 0.013) and with professional assistance (AOR = 0.27, p = 0.039) had a lower risk of mortality. On the other hand, infants with succeeding birth interval less than 24 months (AOR = 6.66, p = 0.001) and those who were never breastfed (AOR = 1.62, p = 0.044) had a higher risk of mortality. Based on NDHS 2011, birth interval (preceding and succeeding) and baby’s size at birth were identified to be significantly associated with infant mortality. Infants born with preceding birth interval (AOR = 1.94, p = 0.022) or succeeding birth interval (AOR = 3.22, p = 0.002) shorter than 24 months had higher odds of mortality while those born with a very large or larger than average size had significantly lowered odds (AOR = 0.17, p = 0.008) of mortality. Conclusion: IMR and associated risk factors differ between NDHS 2006 and 2011 except ‘succeeding birth interval’ which attained significant status in the both study periods. This study identified the ecological region, birth interval, delivery assistant type, baby’s birth size and breastfeeding status as significant predictors of infant mortality

    Protein Folding Activity of the Ribosome is involved in Yeast Prion Propagation.

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    6AP and GA are potent inhibitors of yeast and mammalian prions and also specific inhibitors of PFAR, the protein-folding activity borne by domain V of the large rRNA of the large subunit of the ribosome. We therefore explored the link between PFAR and yeast prion [PSI(+)] using both PFAR-enriched mutants and site-directed methylation. We demonstrate that PFAR is involved in propagation and de novo formation of [PSI(+)]. PFAR and the yeast heat-shock protein Hsp104 partially compensate each other for [PSI(+)] propagation. Our data also provide insight into new functions for the ribosome in basal thermotolerance and heat-shocked protein refolding. PFAR is thus an evolutionarily conserved cell component implicated in the prion life cycle, and we propose that it could be a potential therapeutic target for human protein misfolding diseases

    Ligand-Dependent Conformations and Dynamics of the Serotonin 5-HT2A Receptor Determine Its Activation and Membrane-Driven Oligomerization Properties

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    From computational simulations of a serotonin 2A receptor (5-HT2AR) model complexed with pharmacologically and structurally diverse ligands we identify different conformational states and dynamics adopted by the receptor bound to the full agonist 5-HT, the partial agonist LSD, and the inverse agonist Ketanserin. The results from the unbiased all-atom molecular dynamics (MD) simulations show that the three ligands affect differently the known GPCR activation elements including the toggle switch at W6.48, the changes in the ionic lock between E6.30 and R3.50 of the DRY motif in TM3, and the dynamics of the NPxxY motif in TM7. The computational results uncover a sequence of steps connecting these experimentally-identified elements of GPCR activation. The differences among the properties of the receptor molecule interacting with the ligands correlate with their distinct pharmacological properties. Combining these results with quantitative analysis of membrane deformation obtained with our new method (Mondal et al, Biophysical Journal 2011), we show that distinct conformational rearrangements produced by the three ligands also elicit different responses in the surrounding membrane. The differential reorganization of the receptor environment is reflected in (i)-the involvement of cholesterol in the activation of the 5-HT2AR, and (ii)-different extents and patterns of membrane deformations. These findings are discussed in the context of their likely functional consequences and a predicted mechanism of ligand-specific GPCR oligomerization

    Meeting Future Energy Needs in the Hindu Kush Himalaya

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    As mentioned in earlier chapters, the HKH regions form the entirety of some countries, a major part of other countries, and a small percentage of yet others. Because of this, when we speak about meeting the energy needs of the HKH region we need to be clear that we are not necessarily talking about the countries that host the HKH, but the clearly delineated mountainous regions that form the HKH within these countries. It then immediately becomes clear that energy provisioning has to be done in a mountain context characterized by low densities of population, low incomes, dispersed populations, grossly underdeveloped markets, low capabilities, and poor economies of scale. In other words, the energy policies and strategies for the HKH region have to be specific to these mountain contexts

    Centrality and transverse momentum dependence of D-0-meson production at mid-rapidity in Au plus Au collisions ats root S-NN=200 GeV

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