Role of the rdxA and frxA genes in oxygen-dependent metronidazole resistance of Helicobacter pylori

Almost 50 % of all Helicobacter pylori isolates are resistant to metronidazole, which reduces the efficacy of metronidazole-containing regimens, but does not make them completely ineffective. This discrepancy between in vitro metronidazole resistance and treatment outcome may partially be explained by changes in oxygen pressure in the gastric environment, as metronidazole-resistant (MtzR) H. pylori isolates become metronidazole-susceptible (MtzS) under low oxygen conditions in vitro. In H. pylori the rdxA and frxA genes encode reductases which are required for the activation of metronidazole, and inactivation of these genes results in metronidazole resistance. Here the role of inactivating mutations in these genes on the reversibility of metronidazole resistance under low oxygen conditions is established. Clinical H. pylori isolates containing mutations resulting in a truncated RdxA and/or FrxA protein were selected and incubated under anaerobic conditions, and the effect of these conditions on the MICs of metronidazole, amoxycillin, clarithromycin and tetracycline, and cell viability were determined. While anaerobiosis had no effect on amoxycillin, clarithromycin and tetracycline resistance, all isolates lost their metronidazole resistance when cultured under anaerobic conditions. This loss of metronidazole resistance also occurred in the presence of the protein synthesis inhibitor chloramphenicol. Thus, factor(s) that activate metronidazole under low oxygen tension are not specifically induced by low oxygen conditions, but are already present under microaerophilic conditions. As there were no significant differences in cell viability between the clinical isolates, it is likely that neither the rdxA nor the frxA gene participates in the reversibility of metronidazole resistance

Сутність адміністративного права за новою класифікацією юриспруденції

На основі новітніх підходів до розумінні завдань, об’єктів і класифікації юридичних наук запропонована перспектива розвитку адміністративного права і процесу, які повинні трансформуватися в нові юридичні науки: базисноантиделыктне «Адміністра­тивне право України», процедурне «Админо­регламентное право України» та у низку регулятивних юридичних наук, а також розробити Адміністративний кодекс України, Адміно-регламентній кодекс України, відповідні регулятивні кодекси.На основе новейших подходов к понимании задач, объектов и классификации юридических наук предложена перспектива развития административного права и процес­са, которые должны трансформироваться в новые юридические науки: базисноанти­деликтное «Административное право Украины», процедурное «Админо­регламентное право Украины» и ряд регулятивных юридических наук, а также разработать Административный кодекс Украины, Админо-регламентный кодекс Украины, соответствую­щие регулятивные кодексы.On the basis of the newest fittings to for understanding of tasks, objects and classification of legal sciences the prospect of development of administrative law and process is offered, which must be transformed in new legal sciences: basisuntidelictical the «Administrative law of Ukraine», procedural «Administrative-reglamental law of Ukraine» and the row of regulative legal sciences, and also to develop the Administrative code of Ukraine, Administrative­-reglamental code of Ukraine, proper regulative codes

Transient early wheeze and lung function in early childhood associated with chronic obstructive pulmonary disease genes

Background It has been hypothesized that a disturbed early lung development underlies the susceptibility to chronic obstructive pulmonary disease (COPD). Little is known about whether subjects genetically predisposed to COPD show their first symptoms or reduced lung function in c

Development of endotoxin tolerance does not influence the response to a challenge with the mucosal live-attenuated influenza vaccine in humans in vivo

Introduction: The effects of bacterial infections on the response to subsequent viral infections are largely unknown. This is important to elucidate to increase insight into the pathophysiology of bacterial and viral co-infections, and to assess whether bacterial infections may influence the course of viral infections. Methods: Healthy male subjects received either bacterial endotoxin [Escherichia coli-derived lipopolysaccharide (LPS), 2 ng/kg, n = 15] or placebo (n = 15) intravenously, followed by intranasal Fluenz (live-attenuated influenza vaccine) 1 week later. Results: LPS administration resulted in increased plasma cytokine levels and development of endotoxin tolerance in vivo and ex vivo, illustrated by attenuated cytokine production upon rechallenge with LPS. Following Fluenz administration, infectivity for the Fluenz A/B strains was similar between the LPS-Fluenz and placebo-Fluenz groups (13/15 subjects in both groups). Also, the Fluenz-induced increase in temperature and IL-6, G-CSF and IP-10 concentrations in nasal wash were similar between both groups. Conclusion: While endotoxemia profoundly attenuates the immune response upon a second LPS challenge, it does not influence the Fluenz-induced immune response. These results suggest immune suppression after bacterial infection does not alter the response to a subsequent viral infection

Is upper gastrointestinal radiography a cost-effective alternative to a Helicobacter pylori “Test and Treat” strategy for patients with suspected peptic ulcer disease?

Current clinical consensus supports an initial Helicobacter pylori (HP) “test and treat” approach when compared to immediate endoscopy for patients with suspected peptic ulcer disease. Alternative diagnostic approaches that incorporate upper GI radiography (UGI) have not been previously evaluated. We sought to determine the cost effectiveness of UGI compared to a HP test and treat strategy, incorporating recent data addressing the reduced prevalence of HP, lower cost of diagnostic interventions, and reduced attribution of PUD to HP. METHODS : Using decision analysis, three diagnostic and treatment strategies were evaluated: 1) Test and Treat —initial HP serology, treat patients who test positive with HP eradication and antiulcer therapy; 2) Initial UGI series —treat all patients with documented ulcer disease with HP eradication and antiulcer therapy; and 3) Initial UGI series, HP serology if ulcer present — treat ulcer and HP based on diagnostic test results. RESULTS : The estimated cost per ulcer cured for each strategy were as follows: test and treat, $3,025; initial UGI,$3,690; and UGI with serology, $3,790. The estimated cost per patient treatment were: test and treat,$498; initial UGI, $610; and UGI with serology,$620. When UGI reimbursement was decreased to less than $50, the UGI strategies yielded a lower cost per patient treated than the test and treat strategy. CONCLUSION : At the current level of reimbursement, UGI should not be considered a cost-effective alternative to the HP test and treat strategy for the initial evaluation of patients with suspected peptic ulcer disease.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73722/1/j.1572-0241.2000.01837.x.pd

Meta-analysis in more than 17,900 cases of ischemic stroke reveals a novel association at 12q24.12

Results: In an overall analysis of 17,970 cases of ischemic stroke and 70,764 controls, we identified a novel association on chromosome 12q24 (rs10744777, odds ratio [OR] 1.10 [1.07-1.13], p 5 7.12 3 10-11) with ischemic stroke. The association was with all ischemic stroke rather than an individual stroke subtype, with similar effect sizes seen in different stroke subtypes. There was no association with intracerebral hemorrhage (OR 1.03 [0.90-1.17], p 5 0.695).Conclusion: Our results show, for the first time, a genetic risk locus associated with ischemic stroke as a whole, rather than in a subtype-specific manner. This finding was not associated with intracerebral hemorrhage.Methods: Using the Immunochip, we genotyped 3,420 ischemic stroke cases and 6,821 controls. After imputation we meta-analyzed the results with imputed GWAS data from 3,548 case

Glycemic control during consecutive days with prolonged walking exercise in individuals with type 1 diabetes mellitus

Aims: Despite its general benefits for health, exercise complicates the maintenance of stable blood glucose concentrations in individuals with type 1 diabetes. The aim of the current study was to examine changes in food intake, insulin administration, and 24-h glycemic control in response to consecutive days with prolonged walking exercise (~8 h daily) in individuals with type 1 diabetes. Methods: Ten individuals with type 1 diabetes participating in the worlds' largest walking event were recruited for this observational study. Simultaneous measurements of 24-h glycemic control (continuous glucose monitoring), insulin administration and food intake were performed during a non-walking day (control) and during three subsequent days with prolonged walking exercise (daily distance 40 or 50 km). Results: Despite an increase in daily energy (31 ± 18%; p 10 mmol/L) and hypoglycemia (blood glucose 0.05 for all variables). The prolonged walking exercise was associated with a modest increase in glycemic variability compared with the control day (p < 0.05). Conclusion: Prolonged walking exercise allows for profound reductions in daily insulin administration in persons with type 1 diabetes, despite large increments in energy and carbohydrate intake. When taking such adjustments into account, prolonged moderate-intensity exercise does not necessarily impair 24-h glycemic control. © 2016 Elsevier Ireland Ltd