A Randomized, Double-Blind Study of Larazotide Acetate to Prevent the Activation of Celiac Disease During Gluten Challenge

OBJECTIVES: In patients with celiac disease, enteropathy is caused by the entry of gluten peptides into the lamina propria of the intestine, in which their immunogenicity is potentiated by tissue transglutaminase (tTG) and T-helper type 1–mediated immune responses are triggered. Tight junction disassembly and paracellular permeability are believed to have an important role in the transport of gluten peptides to the lamina propria. Larazotide acetate is a tight-junction regulator peptide that, in vitro, prevents the opening of intestinal epithelial tight junctions. The aim of this study was to evaluate the efficacy and tolerability of larazotide acetate in protecting against gluten-induced intestinal permeability and gastrointestinal symptom severity in patients with celiac disease. METHODS: In this dose-ranging, placebo-controlled study, 86 patients with celiac disease controlled through diet were randomly assigned to larazotide acetate (0.25, 1, 4, or 8 mg) or placebo three times per day with or without gluten challenge (2.4 g/day) for 14 days. The primary efficacy outcome was the urinary lactulose/mannitol (LAMA) fractional excretion ratio. Secondary endpoints included gastrointestinal symptom severity, quality-of-life measures, and antibodies to tTG. RESULTS: LAMA measurements were highly variable in the outpatient setting. The increase in LAMA ratio associated with the gluten challenge was not statistically significantly greater than the increase in the gluten-free control. Among patients receiving the gluten challenge, the difference in the LAMA ratios for the larazotide acetate and placebo groups was not statistically significant. However, larazotide acetate appeared to limit gluten-induced worsening of gastrointestinal symptom severity as measured by the Gastrointestinal Symptom Rating Scale at some lower doses but not at the higher dose. Symptoms worsened significantly in the gluten challenge–placebo arm compared with the placebo–placebo arm, suggesting that 2.4 g of gluten per day is sufficient to induce reproducible gluten toxicity. Larazotide acetate was generally well tolerated. No serious adverse events were observed. The most common adverse events were headache and urinary tract infection. CONCLUSIONS: LAMA variability in the outpatient setting precluded accurate assessment of the effect of larazotide acetate on intestinal permeability. However, some lower doses of larazotide acetate appeared to prevent the increase in gastrointestinal symptom severity induced by gluten challenge

Comparison of the prevalence and characteristics of inpatient adverse events using medical records review and incident reporting

Background. Information on adverse events (AEs) in hospitalised patients in developing countries is scanty.Objective. To compare the magnitude and characteristics of inpatient AEs in a tertiary, not-for-profit healthcare facility in Kenya, using medical records review and incident reporting.Methods. Estimation of prevalence was done using incidents reported in 2010 from a random sample of medical records for hospital admissions. Nurse reviewers used 18 screening criteria, followed by physician reviewers to confirm occurrence. An AE was defined as an unexpected clinical event (UE) associated with death, disability or prolonged hospitalisation not explained by the disease condition. The kappa statistic was used to estimate inter-rater agreement, and analysis was done using logistic regression.Results. The study identified 53 UEs from 2 000 randomly selected medical records and 33 reported UEs from 23 026 admissions in the index year. The prevalences of AEs from medical records review and incident reports were 1.4% (95% confidence interval (CI) 0.9 - 2.0) and 0.03% (95% CI 0.012 - 0.063), respectively. Compared with incident reporting, review of medical records identified more disability (13.2% v. 0%; p=0.03) and prolonged hospital stays (43.4% v. 18.2%; p=0.02).Conclusions. Review of medical records is preferable to incident reporting in determining the prevalence of AEs in health facilities with limited inpatient quality improvement experience. Further research is needed to determine whether staff education and a positive culture change through promotion of non-punitive UE reporting or a combination of approaches would improve the comprehensiveness of AE reporting

Discovery Potential for Low-Scale Gauge Mediation at Early LHC

Low-scale gauge-mediated supersymmetry(SUSY)-breaking (GMSB) models with gravitino mass m_{3/2}<16 eV are attractive, since there are no flavor and cosmological problems. In this paper, we thoroughly study the collider signal in the case that the next-to-lightest SUSY particle is the bino or slepton and investigate the discovery potential of the LHC. Our result is applicable to a wider class of GMSB models other than the minimal GMSB models and we pay particular attention to realistic experimental setups. We also apply our analysis to the minimal GMSB models with a metastable SUSY-breaking vacuum and we show, by requiring sufficient stability of the SUSY-breaking vacuum, these models can be tested at an early stage of the LHC.Comment: 21 pages, 7 figures.Texts in section 3.2.2 and 3.2.4 are revised. Captions change

The Functionality of the three-sited Ferroxidase center of E. coli Bacterial Ferritin (EcFtnA)

At least three ferritins are found in the bacterium Escherichia coli, the heme-containing bacterioferritin (EcBFR) and two non-heme bacterial ferritins (EcFtnA and EcFtnB). In addition to the conserved A- and B-sites of the diiron ferroxidase center, EcFtnA has a third iron-binding site (the C-site) of unknown function that is nearby the diiron site. In the present work, the complex chemistry of iron oxidation and deposition in EcFtnA has been further defined through a combination of oximetry, pH stat, stopped-flow and conventional kinetics, UV-visible, fluorescence and EPR spectroscopic measurements on the wildtype protein and site-directed variants of the A-, B- and C-sites. The data reveal that, while H2O2 is a product of dioxygen reduction in EcFtnA and oxidation occurs with a stoichiometry of Fe(II)/O2 ~ 3:1, most of the H2O2 produced is consumed in subsequent reactions with a 2:1 Fe(II)/H2O2 stoichiometry, thus suppressing hydroxyl radical formation. While the A- and B-sites are essential for rapid iron oxidation, the C-site slows oxidation and suppresses iron turnover at the ferroxidase center. A tyrosyl radical, assigned to Tyr24 near the ferroxidase center, is formed during iron oxidation and its possible significance to the function of the protein is discussed. Taken as a whole, the data indicate that there are multiple iron-oxidation pathways in EcFtnA with O2 and H2O2 as oxidants. Furthermore, the data are inconsistent with the C-site being a transit site, providing iron to the A- and B-sites, and does not support a universal mechanism for iron oxidation in all ferritins as recently proposed

Photocatalytic oxidation of pollutants in gas-phase via Ag3PO4-based semiconductor photocatalysts: Recent progress, new trends, and future perspectives

Air pollution has become a significant challenge for both developing and developed nations. due to its close association with numerous fatal diseases such as cancer, respiratory, heart attack, and brain stroke. Over recent years, heterogeneous semiconductor photocatalysis has emerged as an effective approach to air remediation due to the ease of scale-up, ready application in the field, use of solar light and ready availability of a number of different effective photocatalysts. To date, most work in this area has been conducted using UV-absorbing photocatalysts, such as TiO2 and ZnO; However, recent studies have revealed Ag3PO4 as an attractive, visible-light-absorbing alternative, with a bandgap of 2.43 eV. In particular, this material has been shown to be an excellent photocatalyst for the removal of many types of pollutants in the gas phase. However, the widespread application of Ag3PO4 is restricted due to its tendency to undergo photoanodic corrosion and the poor reducing power of its photogenerated conductance band electrons, which are unable to reduce O2 to superoxide •O2−. These limitations are critically evaluated in this review. In addition, recent studies on the modification of Ag3PO4 via combination with the conventional heterojunctions or Z-scheme junctions, as well as the photocatalytic mechanistic pathways for enhanced gas-pollutants removal, are summarized and discussed. Finally, an overview is given on the future developments that are required in order to overcome these challenges and so stimulate further research into this promising field

Muon Anomalous Magnetic Moment and mu -> e gamma in B-L Model with Inverse Seesaw

We study the anomalous magnetic moment of the muon, a_\mu, and lepton flavor violating decay \mu -> e \gamma in TeV scale B-L extension of the Standard Model (SM) with inverse seesaw mechanism. We show that the B-L contributions to a_\mu are severely constrained, therefore the SM contribution remains intact. We also emphasize that the current experimental limit of BR(\mu -> e \gamma) can be satisfied for a wide range of parameter space and it can be within the reach of MEG experiment.Comment: 10 pages, 4 Figure