The intestinal motility-promoting effect of pantethine was examined in rabbits, dogs and mice under various anesthetic conditions. In rabbits (Trendelenburg's method), the effect was easily detectable when the animals were anesthetized with pentobarbital or urethane or immobilized with d-tubocurarine chloride, but not in the case of α-chloralose anesthesia. In dogs (balloon method), on the contrary, the effect was easier to be detected under α-chloralose anesthesia rather than urethane anesthesia. On the other hand, the promotive effect of pantethine on the passage of charcoal meal through mouse intestine could not be found under anesthesia with urethane or α-chloralose, though it was detectable under pentobarbital anesthesia. The effect of pantethine concerned was considered to be chlinergic as it was augmented by neostigmine and antagonized by atropine. The influence of anesthetics on the effects of pantothenic acid, neostigmine, carpronium chloride and bethanechol chloride have also been described.
The intravenous, intraperitoneal, subcutaneous and oral acute toxicities of thiotic acid were investigated in Sprague-Dawley rats. The minimal lethal dose of the drug was 150mg/kg after intravenous administration. One and six months toxicity tests using Sprague-Dawley rats were carried out with subcutaneous doses of 8, 16, 32, 64 and 125mg/kg. In these tests, the minimal lethal dose of thioctic acid was 125mg/kg. This was about one half of its LD50. Abnormal changes related to the drug were not observed in systemic signs, values of laboratory tests and histopathological findings.
The diuretic effects of hypotensive diuretics in spontaneously hypertensive rats (SHR) were compared to that of normal rats (NR). Furthermore, the combination effect in SHR and NR was studied. The following results were obtained; (1) SHR had most favorable and stronger sensitivity with hydroflumethiazide (HFT) administration. (2) SHR had a stronger sensitivity on the potassium sparing effect of triamterene (TAT). (3) SHR had also strong sensitivity on the diuretic effects of methyclothiazide (MCT), hydrochlorothiazide (HCT), furosemide (Fur) and clorexolone (Clo) which are potent in NR. (4) In SHR, spironolactone (SPL) showed dose-dependent saluresis which was simultaneously accompanied with kaliuresis. (5) In SHR, mercaptomerine and aminophylline had no diuretic effect. (6) In NR, combining MCT, HFT, HCT and acetazolamide (ACT) to TAT, all cases showed synergism. (7) In SHR, combining MCT, HFT, and HCT to TAT, a more excellent synergism was seen than in NR. Particularly, a combination of TAT and HFT resulted in the highest Na+/K+ excretion ratio. (8) In NR, combinig MCT, HFT and HCT to SPL, weak synergism was seen. (9) Combination MCT to SPL showed little synergism in SHR. (10) When ACT was combined with TAT or SPL in SHR, the diuretic effect decreased more than in a single administration.
A comparative study on the central inhibitory action of Dipotassium chlorazepate (CAP) and Diazepam was performed. The EEG and evoked potential were studied electrophysiologically in the neocortex and limbic system, and comparative studies on the antagonism against various convulsants or central stimulants were also performed. The above comparative studies of the two drugs have found CAP exhibiting a wider range of inhibition than Deazepam. As for the intensity of inhibition, in general, Diazepam was found to be a little stronger than CAP.
The influence of DL-Methionine and Thioctic acid on the experimentally injured liver in rabbits, were investigated. The injury was produced by subcutaneous injection of DL-Ethionine in daily dosage of 100mg/kg for three days. DL-Methionine and Thioctic acid were injected subcutaneously for six days before liver injury. Liver function tests, such as serum GOT, GPT, liver supernated GOT, GPT, and serum cholesterol were examined. Electronmicroscopical examination of the liver, were also performed. The observed findings were that DL-Methionine and Thioctic acid appeared to inhibit the liver injury to a certain degree, and that Thioctic acid appeared to be more effective than DL-Methionine.
Pharmacological properties of a new minor tranquilizer, dipotassium chlorazepate (CAP) were examined. The results obtained were as follows: (1) CAP in lower doses had no significant effects on cardiovascular or respiratory system. Cardiovascular changes induced by acetylcholine or nicotine, except epinephrine were not affected by CAP. Cardiovascular change induced by epinephrine was potentiated by the preadministration of CAP. (2) CAP had no ganglion blocking action. (3) CAP did not affect on monosynaptic reflex, but it had inhibitory effect on polysynaptic reflex. (4) CAP had no effect on neuromuscular junction. (5) CAP at lower doses had almost no effect on isolated atria, intestine and uterus, and at higher doses it had no antihistaminic action. (6) CAP had almost no effect on carrageenin induced edema and pigment transduction. (7) CAP had no significant effects on urinary volume and urinary electrolyte excretion. (8) CAP had no effect on the size of pupil. (9) CAP decreased both normal body temperature and pyrogene induced hyperthermia.
The increase in urinary catecholamine in the animals subjected to cold has been observed by many authors. Also it is demonstrated by several investigators that norepinephrine (NE) and epinephrine (E) released from sympathetic nervous system and adrenal glands produced an increase in plasma NEFA and glucose as fuels. This experiment dealt with the effects of a tyrosine hydroxylase inhibitor, α-methyl-p-tyrosine (α-MPT) and of cold stress on tissue NE, plasma NEFA, glucose and colonic temperature in warm- and cold-acclimated rats to investigate the physiological significance of sympathetic nervous system in the regulation of metabolism for maintaining their body temperature. In rats exposed to cold for 4 weeks, the utilization of heart NE is accelerated during the first week. After cold-acclimation has been accomplished, it appears that NE utilization is decreased. Under such experimental conditions it appears that NEFA and glucose play a compensatory role for maintaining body temperature and that plasma glucose acts as a more effective energy source in withstanding cold stress than plasma NEFA. This experiment suggests that after adult control rats (wt. approx. 300 gr) had been subjected to severe cold stress for several hr, the pattern of biosynthesis and utilization of catecholamine in vivo, did not differ greatly from those of the cold-acclimated rats.
It is well established fact that calcium and phosphorus are vital requirement for the body. This study was carried out in order to examine whether or not teratogenic effects would appear in Wistar albino rat's where the mother had been given a calcium and phosphorus deficient diet during pregnancy. 50 adult females were fed on a diet consisting of Sucrose 69%, Casein 20%, Soybean oil 5%, Salt mixture 5%, Vitamin mixture 0.5% and Choline chloride 0.5%. All rats were provided with distilled water for drinking. Results are as follows: 1) As for ossification retardation of the occipital bone in the groups fed on the said diet for the first 7 days and the middle 7 days, no difference was observed compared with the control group. 2) Beyond the above report, the experimental group was not found to be superior to the control group.