Acute and long-term effects of metformin on the function and insulin secretory responsiveness of clonal β-cells

Functional effects of acute and prolonged (48 h) exposure to the biguanide drug metformin were examined in the clonal pancreatic ß-cell line, BRIN-BD11. Effects of metformin on prolonged exposure to excessive increased concentrations of glucose and palmitic acid were also assessed. In acute 20-min incubations, 12.5-50 µm metformin did not alter basal (1.1 mm glucose) or glucose-stimulated (16.7 mm glucose) insulin secretion. However, higher concentrations of metformin (100-1000 µm) increased (1.3-1.5-fold; p

The MacDQoL individualized measure of the impact of macular degeneration on quality of life: reliability and responsiveness

PURPOSE: To investigate the MacDQoL test-retest reliability and sensitivity to change in vision over a period of one year in a sample of patients with age-related macular degeneration (AMD). DESIGN: A prospective, observational study. METHOD: Patients with AMD from an ophthalmologist's list (n = 135) completed the MacDQoL questionnaire by telephone interview and underwent a vision assessment on two occasions, one year apart. RESULTS: Among participants whose vision was stable over one year (n = 87), MacDQoL scores at baseline and follow-up were highly correlated (r = 0.95; P < .0001). Twelve of the 22 scale items had intraclass correlations of >.80; only two were correlated <.7. There was no difference between baseline and follow-up scores (P = .85), indicating excellent test-retest reliability. Poorer quality of life (QoL) at follow-up, measured by the MacDQoL present QoL overview item, was associated with deterioration in both the better eye and binocular distance visual acuity [VA] (r = 0.29; P = .001, r = 0.21; P = .016, respectively; n = 135). There was a positive correlation between deterioration in the Mac. DQoL average weighted impact score and deterioration in both binocular near VA and reading speed (r = 0.20; P = .019, r = 0.18; P = .041, respectively; n = 135). CONCLUSION: The MacDQoL has excellent test-retest reliability. Its sensitivity to change in vision status was demonstrated in correlational analyses. The measure indicates that the negative impact of AMD on QoL increases with increasing severity of visual impairment.

Vascular cell responsiveness to toll-like receptor ligands in carotid atheroma

Background Atherosclerosis is potentiated by stimulation of Toll-like receptors (TLRs), which serve to detect pathogen associated molecular patterns (PAMPs). However little is known of which PAMPs may be present in atheroma, or capable of stimulating inflammatory signalling in vascular cells. Materials and Methods DNA extracted from human carotid atheroma samples was amplified and sequenced using broad-range 16S gene specific primers to establish historical exposure to bacterial PAMPs. Responsiveness of primary human arterial and venous endothelial and smooth muscle cells to PAMPs specific for each of the TLRs was assessed by measurement of interleukin-8 secretion and E-selectin expression. Results Extracts of atheromatous tissue stimulated little or no signalling in TLR-transfected HEK-293 cells. However, sequencing of bacterial DNA amplified from carotid atheroma revealed the presence of DNA from 17 different bacterial genera, suggesting historical exposure to bacterial lipopeptide, lipopolysaccharide and flagellin. All cells examined were responsive to the ligands of TLR3 and TLR4, poly inosine:cytosine and lipopolysaccharide. Arterial cells were responsive to a wider range of PAMPs than venous cells, being additionally responsive to bacterial flagellin and unmethylated cytosine-phosphate-guanosine DNA motifs, the ligands of TLR5 and TLR9, respectively. Cells were generally unresponsive towards the ligands of human TLR7 and TLR8, loxoribine and single stranded RNA. Only coronary artery endothelial cells expressed TLR2 mRNA and responded to the TLR2 ligand Pam3CSK4. Conclusions Vascular cells are responsive to a relatively diverse range of TLR ligands and may be exposed, at least transiently, to ligands of TLR2, TLR4, TLR5 and TLR9 during the development of carotid atheroma.

Evacuation responsiveness by government organisations (ERGO):the evacuation preparedness assessment workbook

This Evacuation Preparedness Assessment Workbook (EPAW) is a tool to assess the level of preparedness of Government Organisations (GOs) for the mass evacuation of their public. It has its origins in the results of a three-year, EU-funded research project called Evacuation Preparedness by Government Organisations (ERGO) which sought to research and strengthen the preparedness activities for the evacuation of cities, regions or even countries. This EPAW presents a list of tasks to be carried out at the different phases of evacuation preparedness. It also provides an assessment facility to evaluate how much progress GOs have made against each task, as well as indications of standard and best practices for each task. A brief background to the need for evacuation, the ERGO project and the development of the workbook is given next. After this, the application process of the workbook is explained and illustrated with an example.

Acute and long-term effects of peroxisome proliferator-activated receptor-γ activation on the function and insulin secretory responsiveness of clonal beta-cells

Thiazolidinediones (TZDs) are used as antidiabetic therapy. The purpose of the present study was to examine whether the TZD rosiglitazone has direct actions on pancreatic beta-cells that contribute to its overall effects. Effects of acute and prolonged (48 h) exposure to rosiglitazone, as a model glitazone compound, were assessed in clonal pancreatic BRIN-BD11 beta-cells maintained in standard, glucotoxic and lipotoxic cultures. In acute 20-min incubations, rosiglitazone (0.2-100 M) did not alter basal or glucose-stimulated insulin secretion. However, rosiglitazone (6.25 M) enhanced (p

Regulation of the expression of secretory component by human airway epithelial cells in vitro

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Effects of recombinant human DNase and hypertonic saline on airway inflammation in children with cystic fibrosis

Recombinant human DNase (rhDNase) is an established treatment in cystic fibrosis (CF), but it may liberate cationic mediators bound to DNA in the airways. An alternative mucolytic therapy is hypertonic saline (HS); however, HS may potentiate neutrophilic inflammation. We compared the effect of rhDNase and HS on cationic proinflammatory mediators in CF sputum. In a randomized, crossover trial, 48 children with CF were allocated consecutively to 12 weeks of once-daily 2.5 mg rhDNase, alternate-day 2.5 mg rhDNase, and twice-daily 7% HS. Sputum levels of total interleukin-8 (IL-8), free IL-8, myeloperoxidase, eosinophil cationic protein, and neutrophil elastase (NE) activity were measured before and after each treatment. The change in mediator levels from baseline with daily rhDNase and HS was not significant; however, with alternate-day rhDNase, there was an increase in free IL-8. When changes in mediator levels with daily rhDNase were compared with alternate-day rhDNase and HS, no significant differences were detected. Only changes in NE activity were associated with changes in lung function. In summary, we were unable to show that rhDNase or HS promote airway inflammation in CF.

Nucleoside diphosphate kinase--a component of the [Na+1]- and [Cl-]-sensitive phosphorylation cascade in human and murine airway epithelium

We have shown that proteins within apically enriched fractions of human nasal respiratory epithelium vary their phosphohistidine content with ambient [Cl-] and other anion concentrations. This membrane-delimited phosphorylation cascade includes a multifunctional protein histidine kinase - nucleoside diphosphate kinase (NDPK). NDPK is itself a cascade component in both human and ovine airway, the self-phosphorylation of which is inhibited selectively by [Na+] in the presence of ATP (but not GTP). These findings led us to propose the existence of a dual anion-/cation-controlled phosphorylation-based "sensor" bound to the apical membrane. The present study showed that this cascade uses ATP to phosphorylate a group of proteins above 45 kDa (p45-group, identities unknown). Additionally, the Cl- dependence of ATP (but not GTP) phosphorylation is conditional on phosphatase activity and that interactions exist between the ATP- and GTP-phosphorylated components of the cascade under Cl--free conditions. As a prelude to studies in cystic fibrosis (CF) mice, we showed in the present study that NDPK is present and functionally active in normal murine airway. Since NDPK is essential for UTP synthesis and regulates fetal gut development, G proteins, K+channels, neutrophil-mediated inflammation and pancreatic secretion, the presence of ion-regulated NDPK protein in mouse airway epithelium might aid understanding of the pathogenesis of CF.

Using an in vitro human airway model to study the toxic effects of components of e-cigarettes

Cigarette smoke is a complex mixture of more than 4000 hazardous chemicals including the carcinogenic benzopyrenes. Nicotine, the most potent component of tobacco, is responsible for the addictive nature of cigarettes and is a major component of e-cigarette cartridges. Our study aims to investigate the toxicity of nicotine with special emphasis on the replacement of animals. Furthermore, we intend to study the effect of nicotine, cigarette smoke and e-cigarette vapours on human airways. In our current work, the BEAS 2B human bronchial epithelial cell line was used to analyse the effect of nicotine in isolation, on cell viability. Concentrations of nicotine from 1.1µM to 75µM were added to 5x105 cells per well in a 96 well plate and incubated for 24 hours. Cell titre blue results showed that all the nicotine treated cells were more metabolically active than the control wells (cells alone). These data indicate that, under these conditions, nicotine does not affect cell viability and in fact, suggests that there is a stimulatory effect of nicotine on metabolism. We are now furthering this finding by investigating the pro-inflammatory response of these cells to nicotine by measuring cytokine secretion via ELISA. Further work includes analysing nicotine exposure at different time points and on other epithelial cells lines like Calu-3.

Growth, uniformity, local responsiveness, and system-wide adaptation in multiunit franchising

Using the resource-based view framework, we investigate the link between multiunit franchising (MUF) and performance on four key challenges in franchise chain management: growth, uniformity, local responsiveness, and system-wide adaptation. Our findings support the assertion that system growth is positively related to MUF rate within a system, in particular in relation to geographic expansion. Interestingly, while uniformity does not seem to be related to MUF rate, we find marginal support for an inverted u-shaped relationship between system-wide adaptation and MUF rate. Furthermore, the data suggest that local responsiveness and MUF rate are related in a u-shaped function.

A hazai vállalatok elektronikus beszerzés iránti nyitottsága = E-procurement Responsiveness of the Hungarian Companies’

A Versenyképesség Kutató Központ 2004-ben a „Versenyben a világgal 1995-97.” kutatási program és az 1999-es vállalati versenyképességi kérdőíves felmérés hagyományait folytatva, valamint azok tapasztalataira építve egy hároméves kutatási programot kezdett el „Versenyben a világgal 2004-2006 − Gazdasági versenyképességünk vállalati nézőpontból” címmel. A kérdőíves felmérés nyomán létrejött adatbázist elemeztük hasonló témában 2005-ben. A korábbi eredményeken okulva, a kérdőív-elemzés kiterjesztésével azt kívántuk felmérni, hogy az elektronikus beszerzés iránti nyitottság növekedett-e hazánkban, illetve milyen egyéb összefüggések fedezhetők fel a beszerzési szervezet, a beszerzés vállalati kapcsolatai, valamint az elektronikus beszerzés értelmezésében az egyes válaszadóknál. A kutatás továbbra is eltér a hagyományos megoldásoktól, azaz nem kívánja vizsgálni a hazai vállalati honlapok elterjedtségét, azonban a korábbiaktól eltérően több információ-technológiával kapcsolatos információt kíván a válaszadóktól. A cél, tehát belső vállalati folyamatok, vevő-szállító kapcsolatok, az informatikai háttér elektronikus beszerzéssel való kapcsolatának feltárása és következtetéseink levonása volt annak érdekében, hogy megtudjuk milyen hatékonyságnövelési lehetőséget hordoz az elektronikus beszerzés és a hazai információs társadalmi fejlettség figyelembe vételével mennyire nyitottak erre a beszerzők és a pályázók egyaránt. Az elektronikus beszerzés és versenyképesség kapcsolata különösen a 2000-es éves eleje óta foglalkoztatja a kutatókat. Vita az elektronikus beszerzés beszerzési költségre gyakorolt hatásában, valamint a kormányzati politika által gyakorolt hatás jellegében van, melyet a közbeszerzés mint speciálisan szabályozott beszerzési tevékenység és az e-beszerzés kapcsolatára fejt ki. A vállalatok versenyképességének és az elektronikus beszerzés folyamatosan bővülő és fejlődő eszközrendszerének kapcsolata azonban nem kérdéses, ezt kutatási eredményeink is megerősítik. _________ The Competitiveness Research Center based on the experience of the „ In Global Competition 1995-1997” research programme and continuing the company competitiveness survey (1999) has begun a three-year research programme with the following title: „In Global Competition 2004-2006” Our economic competitiveness, company point of view”. We had analyzed a database generated on the basis of a questionnaire survey with a similar theme in 2005. Drawing the lessons from earlier researches and expanding the questionnaire examination, we now seek to find out how far receptiveness to electronic procurement has increased in Hungary and what other relations can be observed in responses concerning the interpretation of procurement organizations, the corporate aspects of procurement and electronic procurement. The new research project continues to differ from traditional solutions insofar as it does not intend to examine the currency of corporate web pages, but, in contrast to earlier practice, it does want responders to provide information on IT technology. The objectives are thus to understand how electronic procurement relates to corporate processes, purchaser-supplier relations and IT base, and to see what opportunities of increasing efficiency there are in electronic procurement and how far procurers and bidders are open to this at the level of information society development in Hungary. Researchers have focused on the relation between electronic procurement and competitiveness since the early 2000s. What is debated is how electronic procurement influences procurement costs, and how government policies influence the relation between public procurement as a specially regulated procurement activity and electronic procurement. The relation between corporate competitiveness and the continually increasing means of electronic procurement is beyond doubt, evidenced by our research findings.