Background: Contraction of airway smooth muscle is regulated by receptor-coupled mechanisms that control the force developed for a given cytosolic calcium concentration (i.e., calcium sensitivity). Halothane antagonizes acetylcholine-induced increases in calcium sensitivity by inhibiting GTP-binding (G)-protein pathways. The authors tested the hypothesis that hexanol, like halothane, inhibits agonist-induced increases in calcium sensitivity in airway smooth muscle by inhibiting G-protein pathways.
Methods: Calcium sensitivity was assessed using [alpha]-toxin-permeabilized canine tracheal smooth muscle. In selected experiments, regulatory myosin light chain phosphorylation was also determined by Western blotting in the presence and absence of 10 mm hexanol and/or 100 [mu]m acetylcholine.
Results: Hexanol (10 mm) and halothane (0.76 mm) attenuated acetylcholine-induced calcium sensitization by decreasing regulatory myosin light chain phosphorylation during receptor stimulation. Hexanol also inhibited increases in calcium sensitivity due to direct stimulation of heterotrimeric G-proteins with tetrafluoroaluminate but not with 3 [mu]m GTP[gamma]S, consistent with prior results obtained with halothane. In contrast, in the absence of receptor stimulation, both compounds produced a small increase in calcium sensitivity by a G-protein-mediated increase in regulatory myosin light chain phosphorylation that was not affected by pertussis toxin treatment. 相似文献
AIMS: To determine the most appropriate regression models to use when assessing risk factors for severe hypoglycaemia and to investigate the impact of model misspecification and its clinical implications. METHODS: A total of 1229 children with Type 1 diabetes (mean age 11.7 years sd 4.1), of which 605 (49.2%) were males, were studied. Prospective assessment of severe hypoglycaemia (an event leading to loss of consciousness or seizure) was made over the 9-year period, 1992-2001. Patients were seen every 3 months and episodes of hypoglycaemia along with clinical data were recorded. Over 70% of children never experienced a severe hypoglycaemic event. Data were analysed using the Poisson regression, negative binomial, zero-inflated Poisson (ZIP) and zero-inflated negative binomial (ZINB) models. The over-dispersion and likelihood ratio statistics were calculated and the analytical methods compared. RESULTS: The Poisson regression model did not fit the data well. The negative binomial and the zero inflated Poisson and negative binomial models fitted the data better than Poisson. CONCLUSIONS: The commonly used Poisson regression models to analyse hypoglycaemia epidemiology may lead to biased parameter estimates and incorrect determination of risk factors for hypoglycaemia. We recommend the use of the negative binomial or zero inflated models to examine any risk factors associated with severe hypoglycaemia. Careful consideration must be given to the interpretation of hypoglycaemia surveys and their analysis. 相似文献