Rapid Insulinotropic Action of Low Doses of Bisphenol-A on Mouse and Human Islets of Langerhans: Role of Estrogen Receptor β

Bisphenol-A (BPA) is a widespread endocrine-disrupting chemical (EDC) used as the base compound in the manufacture of polycarbonate plastics. It alters pancreatic β-cell function and can be considered a risk factor for type 2 diabetes in rodents. Here we used ERβ−/− mice to study whether ERβ is involved in the rapid regulation of KATP channel activity, calcium signals and insulin release elicited by environmentally relevant doses of BPA (1 nM). We also investigated these effects of BPA in β-cells and whole islets of Langerhans from humans. 1 nM BPA rapidly decreased KATP channel activity, increased glucose-induced [Ca2+]i signals and insulin release in β-cells from WT mice but not in cells from ERβ−/− mice. The rapid reduction in the KATP channel activity and the insulinotropic effect was seen in human cells and islets. BPA actions were stronger in human islets compared to mouse islets when the same BPA concentration was used. Our findings suggest that BPA behaves as a strong estrogen via nuclear ERβ and indicate that results obtained with BPA in mouse β-cells may be extrapolated to humans. This supports that BPA should be considered as a risk factor for metabolic disorders in humans

Combinations of physiologic estrogens with xenoestrogens alter calcium and kinase responses, prolactin release, and membrane estrogen receptor trafficking in rat pituitary cells

<p>Abstract</p> <p>Background</p> <p>Xenoestrogens such as alkylphenols and the structurally related plastic byproduct bisphenol A have recently been shown to act potently via nongenomic signaling pathways and the membrane version of estrogen receptor-α. Though the responses to these compounds are typically measured individually, they usually contaminate organisms that already have endogenous estrogens present. Therefore, we used quantitative medium-throughput screening assays to measure the effects of physiologic estrogens in combination with these xenoestrogens.</p> <p>Methods</p> <p>We studied the effects of low concentrations of endogenous estrogens (estradiol, estriol, and estrone) at 10 pM (representing pre-development levels), and 1 nM (representing higher cycle-dependent and pregnancy levels) in combinations with the same levels of xenoestrogens in GH₃/B6/F10 pituitary cells. These levels of xenoestrogens represent extremely low contamination levels. We monitored calcium entry into cells using Fura-2 fluorescence imaging of single cells. Prolactin release was measured by radio-immunoassay. Extracellular-regulated kinase (1 and 2) phospho-activations and the levels of three estrogen receptors in the cell membrane (ERα, ERβ, and GPER) were measured using a quantitative plate immunoassay of fixed cells either permeabilized or nonpermeabilized (respectively).</p> <p>Results</p> <p>All xenoestrogens caused responses at these concentrations, and had disruptive effects on the actions of physiologic estrogens. Xenoestrogens reduced the % of cells that responded to estradiol via calcium channel opening. They also inhibited the activation (phosphorylation) of extracellular-regulated kinases at some concentrations. They either inhibited or enhanced rapid prolactin release, depending upon concentration. These latter two dose-responses were nonmonotonic, a characteristic of nongenomic estrogenic responses.</p> <p>Conclusions</p> <p>Responses mediated by endogenous estrogens representing different life stages are vulnerable to very low concentrations of these structurally related xenoestrogens. Because of their non-classical dose-responses, they must be studied in detail to pinpoint effective concentrations and the directions of response changes.</p

Rapid streptococcal testing for sore throat and antibiotic resistance

ABSTRACTThis article briefly summarises the arguments for and against the routine use of rapid antigen testing for group A β-haemolytic streptococcal pharyngitis and the deficiencies in the current evidence base in this area. Currently, most commercial tests are immunoassays with a sensitivity of 70–95% (average 85%) and a specificity of 95–99%, depending on the comparator and patient population. Rapid antigen testing is recommended and commonly used in the USA, especially for patients in whom group A β-haemolytic streptococcal infection is clinically likely or who have any symptoms plus direct contact exposure. However, there is no consensus in Europe regarding the role of rapid testing. There remains a need for randomised trials to evaluate its benefit to patients and its cost-effectiveness compared with the main alternatives, including delayed antibiotic prescribing

Low-cost three-channel video for assessment of the clinical consultation.

Single-channel video is an established method for assessing the clinical consultation; however, it has limitations. While previous research has concluded that three-channel video recording of clinical consultations offers advantages, using professional equipment made costs prohibitive. In this study we set out to establish whether the benefits of three-channel video could be achieved using low-budget consumer-level equipment. Using a kit assembled for around euro 1000, we produced three-channel video recordings of simulated consultations. We then showed single- and three-channel versions of the videos to a panel of health professionals and recorded their opinions regarding the quality of the material and the level of information presented. We found that our budget three-channel set-up provided the same advantages as professional three-channel video, while the cost and complexity of the process was minimal. It is now affordable as well as feasible to use a budget set-up three-channel video system for training clinicians and assessing the impact of the computer on the consultation

The feasibility of using UML to compare the impact of different brands of computer system on the clinical consultation.

UK general practice is universally computerised, with computers used in the consulting room at the point of care. Practices use a range of different brands of computer system, which have developed organically to meet the needs of general practitioners and health service managers. Unified Modelling Language (UML) is a standard modelling and specification notation widely used in software engineering

The feasibility of using UML to compare the impact of different brands of computer system on the clinical consultation

UK general practice is universally computerised, with computers used in the consulting room at the point of care. Practices use a range of different brands of computer system, which have developed organically to meet the needs of general practitioners and health service managers. Unified Modelling Language (UML) is a standard modelling and specification notation widely used in software engineering