Familial predisposition of type 1 diabetes mellitus in Japan, a country with low incidence. Japan Diabetes Society Data Committee for Childhood Diabetes.

The study group of the Japan Diabetes Society (JDS) carried out nationwide hospital-based and population-based surveys of childhood type 1 diabetes mellitus (DM) in Japan. According to the nationwide population-based survey, the incidence of childhood type 1 DM in Japan was 1.5 (1.4-1.6)/10(5), which did not differ for the 5 years from 1986-1990. Predisposition for DM and autoimmunity were studied in the first-degree relatives of the patients, including older and later cohorts. The prevalence of type 1 DM was 3.3% (12/369) among siblings and 2.2% (8/369) among parents, while the prevalence of type 2 DM was 0% among siblings and 4.3% (16/369) among parents. The risk of type 1 DM among siblings of the patients was 330 times higher than that among the general population in the Japanese population. The rate of positivity for autoantibodies, including ICA, IAA, GAD and IA-2, was 1.4-2.9% in parents (n=140) and 2.0-3.9% in siblings (n=203). The genetic susceptibility for type 1 DM is far lower in Japanese children than in Caucasian children, but predisposition to the disease and positive autoimmunity are almost the same in Japanese families of patients as in Caucasian families. The quality of life of Japanese parents of children with type 1 DM was less satisfactory that that of the Caucasian parents previously reported, which might be a result of the low incidence of type 1 DM in Japan.

[The effect of the decreased serum concentration of propofol induced by rapid fluid infusion on the spectral edge frequency 90 and median frequency].

The effect of decreased serum concentration of propofol induced by rapid infusion therapy on the EEG was assessed by spectral edge frequency 90% (SEF90) or median frequency (MF) during propofol anesthesia. The eight scheduled surgical patients were administered propofol with a constant rate, and the rapid infusion therapy with 10 ml.kg-1 of acetate Ringer's solution significantly decreased the serum concentration of propofol from 1.96 +/- 0.22 micrograms.ml-1 to 1.68 +/- 0.19 micrograms.ml-1 (approximately 17% reduction). Simultaneous monitoring of SEF90 and MF, however, demonstrated no change during investigation. These results suggest that the mild decrease of the concentration of propofol might not induce the significant change of EEG, or that the reduction of propofol concentration by infusion might be deceptive and produce no significant change in the concentrations of each pharmacological compartment.

Na+ channel block prevents the ischemia-induced release of norepinephrine from spinal cord slices.

The principal finding of the present study with rat spinal cord slices was the novel demonstration of the [Ca2+]o-independent effect of ischemia on norepinephrine release and its antagonism by tetrodotoxin and low temperature (10 degrees C). Our finding that tetrodotoxin antagonized the effects of glucose deprivation on norepinephrine release in a [Ca2+]o-independent way suggests that Na+ channel block alone, i.e., the prevention of Na+ accumulation, may account for the protective action. Low temperature completely prevented the effect of ischemia on norepinephrine release but did not change the release associated with axonal activity. This finding is in good agreement with the observation that small changes in brain temperature critically determine the extent of neuronal injury from ischemia and suggests that both [Ca2+]o-independent release and cell injury are associated with the norepinephrine membrane carrier. It is suggested, therefore, that drugs able to attenuate the increase in [Na+]i during ischemia may be useful agents to protect against ischemic damage if given before the insult.

alpha 2A subtype of presynaptic alpha 2-adrenoceptors modulates the release of [3H]-noradrenaline from rat spinal cord.

The modulation of noradrenaline (NA) release from rat spinal cord slices was investigated and the subtype of presynaptic alpha 2-adrenoceptors involved in the negative feedback modulation was characterized using in vitro perfusion experiments. Rat spinal cord slices were loaded with [3H]NA and the release of radioactivity at rest and in response to field stimulation was determined. The alpha 2-adrenoceptor agonists, clonidine and dexmedetomidine inhibited the stimulation-evoked release of NA from spinal cord slices, whereas alpha 2-adrenoceptor antagonists yohimbine and CH-38083 (7,8-(methylenedioxy)-14-alpha-hydroxyalloberbane HCI), enhanced it. ARC 239, a selective alpha 2B-antagonist, had no effect on the release. In contrast, BRL 44408 a selective alpha 2A-antagonist increased the release of NA. Our results indicate that the negative feedback modulation of NA release from noradrenergic fibres in the spinal cord is mediated via alpha 2A subtype of alpha 2-adrenoceptors.