Dual Effects of Hexanol and Halothane on the Regulation of Calcium Sensitivity in Airway Smooth Muscle

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.     

Evaluating risk factors associated with severe hypoglycaemia in epidemiology studies—what method should we use?

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.     

The dental management of patients with bipolar disorder

Bipolar disorder (manic depressive disease) affects 1% of the United States population. These persons suffer from prolonged episodes of extreme elation and depression. There is a significant incidence of dental pathosis and a need for dental care among these patients. The medications used for the treatment of this disease, their physiologic effects, and their interactions with the drugs used in dentistry are reviewed.     

A microcomputer-based procedure for carrying out rhinomanometry

The determination of nasal airway resistance by the technique of anterior rhinomanometry is made difficult by several factors. Among these are the variability in the breath by breath measurement of airflow and pressure, the effect of under or over breathing, and the ability to produce a smooth transition between inspiration and expiration during which period the measurements are made. To overcome some of these problems a standard procedure has been developed (in our laboratory) for active anterior rhinomanometry. The nasal resistance is calculated from the mean of three sets of three readings with a rest interval between each set. To enable the procedure to be carried out with consistency it has been implemented on a BBC microcomputer. This enables a breathing guide to be provided for the subject, as well as providing a display of each flow pressure curve, a display of the mean curve, plus and minus one standard deviation, and the calculation of left, right and total nasal airway resistance.     

The prevention of cisplatin-induced renal dysfunction by hydroxyl-containing dithiocarbamates.

Two hydroxyl containing dithiocarbamates, sodium N-methyl-D-glucamine dithiocarbamate (NaG) and sodium dihydroxyethyl dithiocarbamate (NaY) have been examined as agents for the control of the renal dysfunction in rats given cisplatin. Of these, NaG was found to be the more effective in controlling such renal dysfunction when administered at 1 and 3 h after 5 mg cisplatin kg-1, i.p. Renal function was examined 5 days after the administration of cisplatin by measurement of serum and urinary levels of creatinine and urea, creatinine clearance, serum and urinary levels of Na+, K+, Mg2+, Ca2+, as well as the concentrations of these ions in the renal medulla and cortex. Treatment of rats given cisplatin with NaG at 1 and 3 h post cisplatin resulted in indices of renal function which were not significantly different from those of animals which had received no cisplatin. The sole difference was found to be a slight increase in renal cortical Na+ concentration.