The thermal change in the hypothalamus, the thermoregulatory center, of the ex perimental animals has been usually measured by use of a thermocouple or a needle formed thermistor inserted through the skull and the brain parenchyma. However, these procedures may be unsuitable for a longterm, observation of the body temperature because the insertion of the thermodes causes considerably widespread damage of the brain tissues, particularly the hypothalamus.Recording the intracardiac, rectal and muscular temperatures of the rabbit by means of the thermistor equipped on the apex of the venous catheter or of the metal-needle, Yasuda (1-3) of this laboratory has reported the influence of various pyrogenic substances on the temperature. Using the same technique, Takashima (4) has compared the effects of pyrogenic substances in the intact and the liver-damaged rabbits.There exist some reports on the tympanic membrane temperature. Benzinger (5) has chosen the tympanic membrane of a human for the measurement of internal body temperature as close as feasible to the hypothalamic heat center. He has introduced 36-gauge twin wires of copper and constantan into the external auditory canal and has placed the thermoelectric junction of the wires at the tympanic membrane. But little work has been done to study the correlation between the brain temperature and the tympanic membrane temperature. The present experiments have been designed to deter mine whether the tympanic membrane temperature changes in parallel with the hypo thalamic temperature or not. In these experiments a decline of the tympanic membrane and brain temperatures was produced by cooling the common carotid arteries or by the administration of some hypothermic agents. An elevation of the temperature was produced by the carotid warming or by the administration of pyrogenic substances. Moreover, the influences of the carotid cooling and warming on behaviors, respiration, blood pressure and heart rate were studied.
METHODSUnanesthetized male albino rabbits, weighting 2.0 to 2.5 kg, were used in the ex periments. All experiments were performed at a room temperature maintained always
5-n-Butyl-l-cyclohexyl-2,4,6-trioxoperhydropyrimidine (BCP), a new antipyretic antiphlogistic agent, has been reported to differ from aminopyrine and phenylbutazone in lack of central convulsion in mice and rats as well as in mildness of the convulsion caused by the toxic doses in rabbits and dogs (1). Respiratory depression was the usual cause of death following excessive doses of BCP. The oral subchronic toxicity of BCP, amino pyrine and phenylbutazone in rats was reported by Okamoto (2) and Araki (3). Accord ing to their results, BCP in the daily doses above 800 mg/kg produced slight degeneration and destruction of the convoluted tubular epithels in the kidney, while phenylbutazone in the lesser doses resulted not only in the similar changes in the kidney, but also in obvious degeneration of the liver cells and the cardiac muscle fibers.The necessary prerequisite of a clinically available drug should be superiority of the main pharmacological effects and also minority of the side effects. During the toxicolo gical studies of the anti phlogistics, the present author found that the lethal dose of BCP in the pregnant rats was markedly different from that in the non-pregnant ones. There fore, attemt has been made in the present report whether the lethal response to the com pound is conditioned by sex or gestation.
METHODSAdult male and female rats (4-5 months of age) of Wistar strain were used. The animals were housed in the individual cage at room temperature of 22±2°C and at humidity of 40-70%, and were fed a commercial powdered diet (CLEA OA-2, supplied by the Japan CLEA Co.) and water ad libitum.Pregnant rats : Previously unmated two female rats were placed in a cage with a male overnight. Those found to have vaginal plugs were isolated and the day when the females showed the positive smear was regarded as zero day of pregnancy.Drug administration : BCP, aminopyrine and phenylbutazone were suspended in water at various concentration with carboxymethyl cellulose and administerd via stomach tube. The non-pregnant rats were treated with a single dose of 1.0, 1.5 and 2.0 g/kg of BCP and were observed for 7 days. In next series of experiments, BCP in doses of 100
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