Ebselen Improves Ischemia-Reperfusion Injury After Rat Lung Transplantation

The heterocyclic organic compound ebselen (2-phenyl-1,2-benizsoselenazol-3(2H)-one) is a glutathione peroxidase mimick with protective properties against oxidative injury. Ebselen also has anti-inflammatory activity, including attenuation of tumor necrosis factor release and increase of interleukin-10, as shown invivo, in inflammatory and ischemia-reperfusion injuries, including those of the lung. This study was designed to assess its effect on severe ischemia-reperfusion injury in a model of left-sided rat lung isotransplantation. Orthotopic single left-sided lung allotransplantation (Wistar to Wistar) was performed in female rats after a total ischemic time of 18h. In nine recipients given 500mg/kg oral ebselen 1h before transplantation, graft PaO2/FiO2 was improved 24h after transplantation, as evidenced with a mean (standard deviation) PaO2 of 139 (61) mmHg vs. eight controls with 65 (33) mmHg (p=0.009). Bronchoalveolar PMN count was reduced to approximately 50% in the ebselen group compared with controls, whereas no difference in the tumor necrosis factor content was found. We conclude that the improvement of lung function in ebselen-treated transplanted rats is mainly the result of the anti-inflammatory activity of the drug during reperfusio

EXonomy analysis for the Inter-domain comparison of electromechanical and pneumatic drives

Today the selection of drive technology for realizing of moving tasks is made by comparing of investment and energy costs in general. Pneumatic drives are characterized by their low purchase price, but at the same time they show high energy consumption in a comparison with electric drives. This general evaluation leads to the point, that in many cases the optimum drive structure for a certain handling task can’t be found regarding functionality and efficiency. To reach that goal, the dynamic, energy and costs characteristics of the actuator have to be observed and summarized. In this paper the EXonomy analysis is presented as a base for the inter-domain comparison of electric and pneumatic drives. Developed EXonomy approach enables the objective analysis and comparison of electric and pneumatic systems within 3 steps

Regulation of Intestinal UDP-Glucuronosyltransferase 1A1 by the Farnesoid X Receptor Agonist Obeticholic Acid Is Controlled by Constitutive Androstane Receptor through Intestinal Maturation

UDP-glucuronosyltransferase (UGT) 1A1 is the only transferase capable of conjugating serum bilirubin. However, temporal delay in the development of the UGT1A1 gene leads to an accumulation of serum bilirubin in newborn children. Neonatal humanized UGT1 (hUGT1) mice, which accumulate severe levels of total serum bilirubin (TSB), were treated by oral gavage with obeticholic acid (OCA), a potent FXR agonist. OCA treatment led to dramatic reduction in TSB levels. Analysis of UGT1A1 expression confirmed that OCA induced intestinal and not hepatic UGT1A1. Interestingly, Cyp2b10, a target gene of the nuclear receptor CAR, was also induced by OCA in intestinal tissue. In neonatal hUGT1/Car(-/-) mice, OCA was unable to induce CYP2B10 and UGT1A1, confirming that CAR and not FXR is involved in the induction of intestinal UGT1A1. However, OCA did induce FXR target genes, such as Shp, in both intestines and liver with induction of Fgf15 in intestinal tissue. Circulating FGF15 activates hepatic FXR and, together with hepatic Shp, blocks Cyp7a1 and Cyp7b1 gene expression, key enzymes in bile acid metabolism. Importantly, the administration of OCA in neonatal hUGT1 mice accelerates intestinal epithelial cell maturation, which directly impacts on induction of the UGT1A1 gene and the reduction in TSB levels. Accelerated intestinal maturation is directly controlled by CAR, since induction of enterocyte marker genes sucrase-isomaitase, alkaline phosphatase 3, and keratin 20 by OCA does not occur in hUGT1/Car(-/-) mice. Thus, new findings link an important role for CAR in intestinal UGT1A1 induction and its role in the intestinal maturation pathway. SIGNIFICANCE STATEMENT Obeticholic acid (OCA) activates FXR target genes in both liver and intestinal tissues while inducing intestinal UGT1A1, which leads to the elimination of serum bilirubin in humanized UGT1 mice. However, the induction of intestinal UGT1A1 and the elimination of bilirubin by OCA is driven entirely by activation of intestinal CAR and not FXR. The elimination of serum bilirubin is based on a CARdependent mechanism that facilitates the acceleration of intestinal epithelium cell differentiation, an event that underlies the induction of intestinal UGT1A1

Mental performance in 8-year-old children fed reduced protein content formula during the 1st year of life: safety analysis of a randomised clinical trial

In humans, maximum brain development occurs between the third trimester of gestation and 2 years of life. Nutrition during these critical windows of rapid brain development might be essential for later cognitive functioning and behaviour. In the last few years, trends on protein recommendations during infancy and childhood have tended to be lower than that in the past. It remains to be demonstrated that lower protein intakes among healthy infants, a part of being able to reduce obesity risk, is safe in terms of mental performance achievement. Secondary analyses of the EU CHOP, a clinical trial in which infants from five European countries were randomised to be fed a higher or a lower protein content formula during the 1st year of life. Children were assessed at the age of 8 years with a neuropsychological battery of tests that included assessments of memory (visual and verbal), attention (visual, selective, focused and sustained), visual-perceptual integration, processing speed, visual-motor coordination, verbal fluency and comprehension, impulsivity/inhibition, flexibility/shifting, working memory, reasoning, visual-spatial skills and decision making. Internalising, externalising and total behaviour problems were assessed using the Child Behaviour Checklist 4\u201318. Adjusted analyses considering factors that could influence neurodevelopment, such as parental education level, maternal smoking, child\u2019s gestational age at birth and head circumference, showed no differences between feeding groups in any of the assessed neuropsychological domains and behaviour. In summary, herewith we report on the safety of lower protein content in infant formulae (closer to the content of human milk) according to long-term mental performance

Rapid growth and childhood obesity are strongly associated with lysoPC(14:0)

BACKGROUND: Despite the growing interest in the early-origins-of-later-disease hypothesis, little is known about the metabolic underpinnings linking infant weight gain and childhood obesity. OBJECTIVE: To discover biomarkers reflective of weight change in the first 6 months and overweight/obesity at age 6 years via a targeted metabolomics approach. DESIGN: This analysis comprised 726 infants from a European multicenter randomized trial (Childhood Obesity Programme, CHOP) for whom plasma blood samples at age 6 months and anthropometric data up to the age of 6 years were available. 'Rapid growth' was defined as a positive difference in weight within the first 6 months of life standardized to WHO growth standards. Weight change was regressed on each of 168 metabolites (acylcarnitines, lysophosphatidylcholines, sphingomyelins, and amino acids). Metabolites significant after Bonferroni's correction were tested as predictors of later overweight/obesity. RESULTS: Among the overall 19 significant metabolites, 4 were associated with rapid growth and 15 were associated with a less-than-ideal weight change. After adjusting for feeding group, only the lysophosphatidylcholine LPCaC14:0 remained significantly associated with rapid weight gain (\u3b2 = 0.18). Only LPCaC14:0 at age 6 months was predictive of overweight/obesity at age 6 years (OR 1.33; 95% CI 1.04-1.69). CONCLUSION: LPCa14:0 is strongly related to rapid growth in infancy and childhood overweight/obesity. This suggests that LPCaC14:0 levels may represent a metabolically programmed effect of infant weight gain on the later obesity risk. However, these results require confirmation by independent cohorts

BMI and recommended levels of physical activity in school children

Background: Physical activity (PA) and its health benefits are a continuous point of discussion. Recommendations for children's daily PA vary between guidelines. To better define the amount of PA necessary to prevent overweight and obesity in children, further research is needed. The present study investigates children's compliance to physical activity guidelines (PAGs) and the association between objectively measured PA and body mass index (BMI). Methods: Participating children were 11 years old (n = 419) and part of the European CHOP trial, which was conducted in Germany, Belgium, Poland, Spain, Italy. At least 2 days of PA measurements were collected from each child using a SenseWear (TM) armband. BMI was calculated from children's height and weight. Thresholds of min.day(-1) in PA needed to differentiate between normal and excess weight (overweight/obesity) were determined with Receiver Operator Characteristics (ROC) analysis. Additionally, adjusted linear and logistic regressions models were calculated for group differences and effects of a 5, 15 and 60 min.day(-1) increases in PA on BMI. Results: Median time spent in total PA was 462 min.day(-1) (25th percentile;75th percentile: 389;534) and 75 min . day(-1) (41;115) in moderate to vigorous PA (MVPA). Girls spent 36 min . day(-1) less in MVPA than boys and overweight/obese children 24 min . day(-1) less than normal weight children (linear regression, p < 0.001). 63.2% of the children met PAGs of 60 min.day(-1) in MVPA. The optimal threshold for min.day(-1) in MVPA determined with ROC analysis was 46 min.day(-1). Comparing 5, 15 and 60 min.day(-1) increases in PA revealed that an additional 15 min.day(-1) of vigorous PA had the same effect as 60 min.day(-1) of MVPA. Sedentary time and light PA showed contrary associations to one another, with light PA being negatively and sedentary time being positively associated with excessive weight. Conclusions: Current PAGs are met by 2/3 of children and seem appropriate to prevent excess weight in children. An official recommendation of daily 15-20 min of vigorous PA and further reduction of sedentary time could help to fight youth overweight and thus be of potential public health importance

Search for single top quarks in the tau+jets channel using 4.8 fb−1^{-1} of ppˉp\bar{p} collision data

We present the first direct search for single top quark production using tau leptons. The search is based on 4.8 fb$^{-1}$ of integrated luminosity collected in $p\bar{p}$ collisions at $\sqrt{s}$=1.96 TeV with the D0 detector at the Fermilab Tevatron Collider. We select events with a final state including an isolated tau lepton, missing transverse energy, two or three jets, one or two of them $b$ tagged. We use a multivariate technique to discriminate signal from background. The number of events observed in data in this final state is consistent with the signal plus background expectation. We set in the tau+jets channel an upper limit on the single top quark cross section of \TauLimObs pb at the 95% C.L. This measurement allows a gain of 4% in expected sensitivity for the observation of single top production when combining it with electron+jets and muon+jets channels already published by the D0 collaboration with 2.3 fb$^{-1}$ of data. We measure a combined cross section of \SuperCombineXSall pb, which is the most precise measurement to date.Comment: 12 pages, 5 figure

b-Jet Identification in the D0 Experiment

Algorithms distinguishing jets originating from b quarks from other jet flavors are important tools in the physics program of the D0 experiment at the Fermilab Tevatron p-pbar collider. This article describes the methods that have been used to identify b-quark jets, exploiting in particular the long lifetimes of b-flavored hadrons, and the calibration of the performance of these algorithms based on collider data.Comment: submitted to Nuclear Instruments and Methods in Physics Research

Measurement of the dijet invariant mass cross section in proton anti-proton collisions at sqrt{s} = 1.96 TeV

The inclusive dijet production double differential cross section as a function of the dijet invariant mass and of the largest absolute rapidity of the two jets with the largest transverse momentum in an event is measured in proton anti-proton collisions at sqrt{s} = 1.96 TeV using 0.7 fb^{-1} integrated luminosity collected with the D0 detector at the Fermilab Tevatron Collider. The measurement is performed in six rapidity regions up to a maximum rapidity of 2.4. Next-to-leading order perturbative QCD predictions are found to be in agreement with the data.Comment: Published in Phys. Lett. B, 693, (2010), 531-538, 8 pages, 2 figures, 6 table