417 research outputs found

    Modulation of β-Cell Ouabain-Sensitive 86Rb+ Influx (Na+/K+ Pump) by D-Glucose, Glibenclamide or Diazoxide

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    The activity of the β-cell Na+/K+ pump was studied by using ouabain-sensitive (lmM ouabain) 86Rb+ influx in β-cell-rich islets of Umeå-ob/ob mice as an indicator of the pump function. The present results show that the stimulatory effect of glucose on ouabain-sensitive 86Rb+ influx reached its approximate maximum at 5mM glucose. Pre-treatment of the islets with 20mM glucose for 60 min strongly reduced the glucose-induced stimulation of the Na+/K+ pump. Pre-treatment (60 or 180 min) of islets at 0mM glucose, on the other hand, did not affect the magnitude of the glucose-induced stimulation of 86Rb+ influx dunng the subsequent 5-min incubation. Glibenclamide stimulated the ouabain-sensitive 86Rb+ uptake in the same manner as glucose. The stimulatory effect, showed its apparent maximum at 0.5μM. Pre-treatment (60 min) of islets with 1μM glibenclamide did not reduce the subsequent stimulation of the ouabain-sensitive 86Rb+ influx. The stimulatory effect of glibenclamide and D-glucose were not .additive, suggesting that they may have the same mechanism of action. No direct effect of glibenclamide (0.01-1μM) was observed on the Na+/K+ ATPase activity in homogenates of islets. Diazoxide (0.4mM) inhibited the Na+/K+ pump. This effect was sustained even after 60 min of pre-treatment of islets with 0.4mM diazoxide. The stimulatory effect of glibenclamide and D-glucose were abolished by diazoxide. It is concluded that nutrient as well as non-nutrient insulin secretagogues activate the Na+/K+ pump, probably as part of the membrane repolarisation process

    D-glucose Stimulates the Na+/K+ Pump in Mouse Pancreatic Islet Cells

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    To determine the effect of D-glucose on the β-cell Na+/K+ pump, 86Rb+ influx was studied in isolated, -cell-rich islets of Umeå-ob/ob mice in the absence or presence of lmM ouabain. D-glucose (20 mM) stimulated the ouabain-sensitive portion of 86Rb+ influx by 65%, whereas the ouabain-resistant portion was inhibited by 48%. The Na+/K+ ATPase activity in homogenates of islets of Umeå-ob/ob mice or normal mice was determined to search for direct effects of D-glucose. Thus, ouabain-sensitive ATP hydrolysis in islet homogenates was measured in the presence of different D-glucose concentrations. No effect of D-glucose (3–20 mM) was observed in either ob/ob or normal islets at the optimal Na+/K+ ratio for the enzyme (135 mM Na+ and 20 mM K+). Neither D-glucose (3–20 mM) nor L-glucose or 3-O-methyl-D-glucose (20 mM) affected the enzyme activity at a high Na+/K+ ratio (175 mM Na+ and 0.7mM K+). Diphenylhydantoin (150 μM) decreased the enzyme activity at optimal Na+/K+ ratio, whereas 50 μM of the drug had no effect. The results suggest that D-glucose induces a net stimulation the Na+/K+ pump of β-cells in intact islets and that D-glucose does not exert any direct effect on the Na+/K+ ATPase activity

    Explainable Information Retrieval: A Survey

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    Explainable information retrieval is an emerging research area aiming to make transparent and trustworthy information retrieval systems. Given the increasing use of complex machine learning models in search systems, explainability is essential in building and auditing responsible information retrieval models. This survey fills a vital gap in the otherwise topically diverse literature of explainable information retrieval. It categorizes and discusses recent explainability methods developed for different application domains in information retrieval, providing a common framework and unifying perspectives. In addition, it reflects on the common concern of evaluating explanations and highlights open challenges and opportunities.Comment: 35 pages, 10 figures. Under revie

    Chlamydia trachomatis

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    Circulating prolactin levels and risk of epithelial ovarian cancer

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    Purpose: Indirect evidence from experimental and epidemiological studies suggests that prolactin may be involved in ovarian cancer development. However, the relationship between circulating prolactin levels and risk of ovarian cancer is unknown. Methods: We conducted a nested case-control study of 230 cases and 432 individually matched controls within three prospective cohorts to evaluate whether pre-diagnostic circulating prolactin is associated with subsequent risk of ovarian cancer. We also assessed whether lifestyle and reproductive factors are associated with circulating prolactin among controls. Results: Prolactin levels were significantly lower among post- versus pre-menopausal women, parous versus nulliparous women, and past versus never users of oral contraceptives in our cross-sectional analysis of controls. In our nested case-control study, we observed a non-significant positive association between circulating prolactin and ovarian cancer risk (ORQ4vsQ1 1.56, 95 % CI 0.94, 2.63, p trend 0.15). Our findings were similar in multivariate-adjusted models and in the subgroup of women who donated blood 655 years prior to diagnosis. We observed a significant positive association between prolactin and risk for the subgroup of women with BMI 6525 kg/m2 (ORQ4vsQ1 3.10, 95 % CI 1.39, 6.90), but not for women with BMI <25 kg/m2 (OR Q4vsQ1 0.81, 95 % CI 0.40, 1.64). Conclusions: Our findings suggest that prolactin may be associated with increased risk of ovarian cancer, particularly in overweight/obese women. Factors associated with reduced risk of ovarian cancer, such as parity and use of oral contraceptives, were associated with lower prolactin levels, which suggests that modulation of prolactin may be a mechanism underlying their association with risk

    Relationship between Chlamydia trachomatis and Mycoplasma genitalium infection and pregnancy rate and outcome in Iranian infertile couples

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    To study the prevalence of C. trachomatis and M. genitalium in a population of infertile couples from Iran and how this relates to tubal factor infertility, pregnancy rate and outcome of pregnancy. Blood, semen and first void urine samples were obtained from 250 infertile couples and 250 fertile women as a control. Infertile couples were followed up after 24 months to determine diagnosis, referral for assisted conception, any pregnancy and pregnancy outcome. Data were analyzed with regard to the results of(i) serological analysis for specific antibodies to C. trachomatis in serum; (ii) the presence of C. trachomatis and M. genitalium DNA in first void urine ; and (iii) in a semen sample of the male partner. Prevalence of C. trachomatis in our study population was comparable to other studies using similar methods and test specimens. No evidence of M. genitalium infection was found. Detection of C. trachomatis in one partner rarely correlated with infection in the other. The risk of tubal factor infertility and the probability of pregnancy and pregnancy outcome were unrelated to the results of serological tests for C. trachomatis antibodies or the presence of C. trachomatis DNA in first void urine of both partners and in a semen sample provided by the male
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