128 research outputs found

    Differential Changes in QTc Duration during In-Hospital Haloperidol Use

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    Aims: To evaluate changes in QT duration during low-dose haloperidol use, and determine associations between clinical variables and potentially dangerous QT prolongation. Methods: In a retrospective cohort study in a tertiary university teaching hospital in The Netherlands, all 1788 patients receiving haloperidol between 2005 and 2007 were studied; ninety-seven were suitable for final analysis. Rate-corrected QT duration (QTc) was measured before, during and after haloperidol use. Clinical variables before haloperidol use and at the time of each ECG recording were retrieved from hospital charts. Mixed model analysis was used to estimate changes in QT duration. Risk factors for potentially dangerous QT prolongation were estimated by logistic regression analysis. Results: Patients with normal before-haloperidol QTc duration (male <= 430 ms, female <= 450 ms) had a significant increase in QTc duration of 23 ms during haloperidol use; twenty-three percent of patients rose to abnormal levels (male >= 450 ms, female >= 470 ms). In contrast, a significant decrease occurred in patients with borderline (male 430-450 ms, female 450-470 ms) or abnormal before-haloperidol QTc duration (15 ms and 46 ms, respectively); twenty-three percent of patients in the borderline group, and only 9% of patients in the abnormal group obtained abnormal levels. Potentially dangerous QTc prolongation was independently associated with surgery before haloperidol use (OR(adj) 34.9, p = 0.009) and before-haloperidol QTc duration (OR(adj) 0.94, p = 0.004). Conclusion: QTc duration during haloperidol use changes differentially, increasing in patients with normal before-haloperidol QTc duration, but decreasing in patients with prolonged before-haloperidol QTc duration. Shorter before-haloperidol QTc duration and surgery before haloperidol use predict potentially dangerous QTc prolongatio

    Physicochemical and textural quality attributes of gluten-free bread formulated with guar gum

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    The objective of this study was to assess the combined effect of guar gum (GG) and water content (WC) on the rheological properties of batter, and the physicochemical and textural properties of bread. Batches of gluten-free bread used a base formulation of rice (50%), maize (30%) and quinoa flour (20%), with different levels of GG (2.5, 3.0 or 3.5%) and water (90, 100 or 110%) in a full factorial design. Higher GG doses (p<0.001) tended to produce batters of lower stickiness, work of adhesion and cohesive strength; yet, of higher firmness, consistency, cohesiveness and viscosity index. These batters yielded loaves of lower (p<0.001) specific volume and baking loss; and crumbs of lower (p<0.001) aw, pH, mean cell area, void fraction, mean cell aspect ratio; and higher (p<0.001) hardness, adhesiveness, springiness, cohesiveness, chewiness, resilience, mean cell density, cell size uniformity and mean cell compactness. The sticker and less consistent batters produced with higher WC rendered larger bread loaves of softer and more cohesive and springy/resilient crumbs with greater mean cell size and void fraction. Gluten-free loaves of good appearance in terms of higher specific volume, lower crumb hardness, higher crumb springiness, and open grain visual texture were obtained in formulations with 110% WC and GG doses between 2.5 and 3.0%.Eng. Encina-Zelada acknowledges the financial aid provided by the Peruvian National Programme of Scholarships and Student Loans (PRONABEC) in the mode of PhD grants (Presidente de la República-183308). The authors are grateful to Eng. Andrea Oliveira from Prodipani, Portugal, for her kind advice and providing breadmaking ingredients.info:eu-repo/semantics/publishedVersio

    Search for the standard model Higgs boson at LEP

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    Relationship of urinary isoprostanes to prostate cancer occurence

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    To estimate the oxidative stress in patients with prostate cancer and in a control group, we used the biomarker of lipid peroxidation–isoprostanes (8-isoPGF2) and the level of selected antioxidants (glucose and uric acid [UA]). The level of urinary isoprostanes was determined in patients and controls using an immunoassay kit according to the manufacturer’s instruction. The levels of UA and glucose were also determined in serum by the use of UA Assay Kit and Glucose Assay Kit. We observed a statistically increased the level of isoprostanes in urine of patients with prostate cancer in compared with a control group. The concentration of tested antioxidants in blood from patients with prostate cancer was also higher than in healthy subjects. Moreover, our experiments indicate that the correlation between the increased amount of UA and the lipid peroxidation exists in prostate cancer patients (in all tested groups). Prostate cancer risk by urinary isoprostanes level was analyzed, and a positive association was found (relative risk for highest vs. lowest quartile of urinary isoprostanes = 1.6; 95 % confidence interval 1.2–2.4; p for trend = 0.03). We suggest that reactive oxygen species induce peroxidation of unsaturated fatty acid in patients with prostate cancer, and the level of isoprostanes may be used as a non-invasive marker for determination of oxidative stress. We also propose that UA may enhance the oxidative stress in patients with prostate cancer.This study was supported by the Grant 506/810(KBO) from University of Lodz, Polan

    Effects of the fungicide metiram in outdoor freshwater microcosms: responses of invertebrates, primary producers and microbes

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    The ecological impact of the dithiocarbamate fungicide metiram was studied in outdoor freshwater microcosms, consisting of 14 enclosures placed in an experimental ditch. The microcosms were treated three times (interval 7 days) with the formulated product BAS 222 28F (Polyram®). Intended metiram concentrations in the overlying water were 0, 4, 12, 36, 108 and 324 μg a.i./L. Responses of zooplankton, macroinvertebrates, phytoplankton, macrophytes, microbes and community metabolism endpoints were investigated. Dissipation half-life (DT50) of metiram was approximately 1–6 h in the water column of the microcosm test system and the metabolites formed were not persistent. Multivariate analysis indicated treatment-related effects on the zooplankton (NOECcommunity = 36 μg a.i./L). Consistent treatment-related effects on the phytoplankton and macroinvertebrate communities and on the sediment microbial community could not be demonstrated or were minor. There was no evidence that metiram affected the biomass, abundance or functioning of aquatic hyphomycetes on decomposing alder leaves. The most sensitive populations in the microcosms comprised representatives of Rotifera with a NOEC of 12 μg a.i./L on isolated sampling days and a NOEC of 36 μg a.i./L on consecutive samplings. At the highest treatment-level populations of Copepoda (zooplankton) and the blue-green alga Anabaena (phytoplankton) also showed a short-term decline on consecutive sampling days (NOEC = 108 μg a.i./L). Indirect effects in the form of short-term increases in the abundance of a few macroinvertebrate and several phytoplankton taxa were also observed. The overall community and population level no-observed-effect concentration (NOECmicrocosm) was 12–36 μg a.i./L. At higher treatment levels, including the test systems that received the highest dose, ecological recovery of affected measurement endpoints was fast (effect period < 8 weeks)

    Deletion of Cryptococcus neoformans AIF Ortholog Promotes Chromosome Aneuploidy and Fluconazole-Resistance in a Metacaspase-Independent Manner

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    Apoptosis is a form of programmed cell death critical for development and homeostasis in multicellular organisms. Apoptosis-like cell death (ALCD) has been described in several fungi, including the opportunistic human pathogen Cryptococcus neoformans. In addition, capsular polysaccharides of C. neoformans are known to induce apoptosis in host immune cells, thereby contributing to its virulence. Our goals were to characterize the apoptotic signaling cascade in C. neoformans as well as its unique features compared to the host machinery to exploit the endogenous fungal apoptotic pathways as a novel antifungal strategy in the future. The dissection of apoptotic pathways revealed that apoptosis-inducing factor (Aif1) and metacaspases (Mca1 and Mca2) are independently required for ALCD in C. neoformans. We show that the apoptotic pathways are required for cell fusion and sporulation during mating, indicating that apoptosis may occur during sexual development. Previous studies showed that antifungal drugs induce ALCD in fungi and that C. neoformans adapts to high concentrations of the antifungal fluconazole (FLC) by acquisition of aneuploidy, especially duplication of chromosome 1 (Chr1). Disruption of aif1, but not the metacaspases, stimulates the emergence of aneuploid subpopulations with Chr1 disomy that are resistant to fluconazole (FLCR) in vitro and in vivo. FLCR isolates in the aif1 background are stable in the absence of the drug, while those in the wild-type background readily revert to FLC sensitivity. We propose that apoptosis orchestrated by Aif1 might eliminate aneuploid cells from the population and defects in this pathway contribute to the selection of aneuploid FLCR subpopulations during treatment. Aneuploid clinical isolates with disomies for chromosomes other than Chr1 exhibit reduced AIF1 expression, suggesting that inactivation of Aif1 might be a novel aneuploidy-tolerating mechanism in fungi that facilitates the selection of antifungal drug resistance
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