Investigating the metabolism of isonicotinic acid hydrazide (INAH) in vivo, the author obtained the following results : 1) In the urine of the rabbit, to which INAH was administered, INAH, INAH-glucose hydrazine (INAH-G) and acetyl. INAH (INAH-Ac) were detected. 2) A new method of quantitative determination of INAH with dinitrofluorobenzene was devised. With this method, free INAH and bound INAH were measured quantitatively. Unstable bound type and stable bound type were measured separately for the bound INAH. 3) The elimination rate of INAH, INAH pyruvate (INAH-pA), INAH-G and INAH-Ac in urine was about 30-70% of administered dose. The elimination rate of free INAH ws ob-served to decrease in the following order : INAH, INAH-pA, and INAH-G administered group. With the INAH-Ac administered group only stable bound type was observed. 4) The pre-treatment with pyruvic acid or glucose did not affect the total elimination rate of INAH and the elimination of bound type. 5) Pyruvic acid and glucose in the blood were observed to increase with the injection of INAH. 6) LD50 of INAH was 190 mg/kg, that of INAH-pA 5560 mg/kg and those of INAH-G and INAH-Ac were 10 g/kg and 20 g/kg respectively for mice with subcutaneous injection. 7) INAH was observed to have dilatating effect on the auricular vessel of rabbit and inhibitoryone on the movement of the isolated intestine of rabbit and the isolated uterus of rat. However with the other 3 bound types, no appreciable effects were observed. 8) Spasm was observed after some latent period with the intravenous injection of INAH in rabbit and the rabbit died with 250 mg/kg. Moderate action was observed with 836 mg/kg of INAH (equivalent to 500 mg/kg INAH), but the rabbit did not die. No action was observed either with 1220 mg/kg of INAH-G or with 652 mg/ kg of INAH-Ac (each equivalent to 500 mg/kg INAH respectively). 9) Pre-treatment with pyruvic acid or glucose did not influence the toxic effect of INAH. 10) With tests in vitro, INAH-pA was observed to have a similar degree of inhibitory action as INAH on the growth of tubercle bacillus. The action of INAH-Ac was weaker. 11) The degree of in vivo action of INAH-pA, INAH-G and INAH-Ac was observed to parallel the degree of liberation of INAH to a considerable extent.
It was proved that the effect of adrenalin on carbohydrate and energetic metabolism in vitro differed from that of NH4C1 in spite of its similarity in vivo. It is suggested from above that the injections of NH4Cl cause acidosis, which increase adrenalin-like substances, and show the adrenalin-like actions in vivo.
The authors observed the influences of such muscle relaxants as d-tubocurarine, etc. upon the gaseous metabolism. By the administration of 0.14 to 0.28 mg of d-tubocurarine chloride per kg of body weight, the gaseous metabolism of rats was inhibited for a comparatively long time, Rig rose, and the body temperature dropped markedly. By 0.02 to 0.05 mg/kg of dimethyl-tubocurarine iodide, the gaseous metabolism was inhibited and the body temperature remained dropped for a long time. By 1.0 to 4 mg/kg of decamethonium, the gaseous metabolism. was, checked and R.Q. and the body temperature fell. When given in doses of 0.25 mg/kg or more, tetrodotoxin (fugu-toxin, a poison of the globe-fish species) inhibited the gaseous metabolism and made the body temperature drop, although those metabolic changes varied more or less in their degree according to a dose of the drug to be administered. When administered in doses of 25 mg/kg or more, mephenesin inhibited the gaseous metabolism for a long while and caused a persisting fall of the body temperature.
The insulin content of the pancreas was determined in dogs and rats which were administered calcium mesoxalate continuously for a prolonged period. 1) The insulin content of the pancreas increased in rats given daily oral doses of 100 mg/kg for 1, 3, 6 and 12 months. The effect of the drug reached the maximum level after 3 months. 2) The pups, 3-6 kg body weight, were.given daily oral doses of 10 mg/kg and 50 mg/kg for 2 and 6 months. After 2 months the insulin content of the pancreas increased to nearly twice the normal value, but after 6 months there was no significant deviation from the normal pattern. Variance by sex was negligible. 3) The male dogs, 10-15 kg body weight, were given daily doses of 50 mg/kg and 200 mg/kg for 1 and 2 months. The maximum effect occurred in the group of dogs administered doses of 200 mg/kg for 1 month, the insulin content rising to two and half times the normal value. But there was no significant deviation from the normal pattern in the group of dogs administered doses of 50 mg/kg for 2 months.
The object of present investigation was to measure the conduction velocity of heart muscle, modifying the method of Bammer and Rothschuh. Using R-C coupled amplifier and a cathode-ray oscillograph, the conduction velocity was estimated by finding the time interval between the stimulus artefact and the action potential. The potential changes usually consisted of QRS-segment and Tspike as shown in ECG, and was influenced by the spontaneous movement, the distance of bipolar recording electrodes and the recording point. The conduction velocity related to the stimulus strength and the concentrations of some ions, especially K· and Ca··. From these results it was found that this method is one of the most excellent procedures to investigate the effect of some drugs on the conduction velocity in toad heart muscle.
In case of single administration of histamine hydrochloride, histamine is not absorbed in the large intestine of rabbit, but is slightly absorbed at the high temperature as 32°C or more. In the combined administrations with various substances, the followings were noted : The absorption of histamine is not promoted by amino acids, but it is evidently promoted by Para-amino-benzoic acid or cattle bile. Especially the promoting action of the latter is more remarkable. Also, some of aromatic carboxylic acids promote the absorption of histamine. The influence of hypertonic or hypo. tonic enema solution containing histamine, and of prior treatments with narcotics on the histamine absorption were not evident.
The relation of the acetylcholine (ACh) formation to the pyruvate metabolism in rat brain tissue was studied. When choline and choline acetylase preparation (CHA) coexisted with the pyruvate metabolism by cyclophorase system (GYP) of rat brain (CHA-CYP-Pyruvate system), the large amount of ACh was produced under the aerobic condition, while negligible under the anaerobic condition. Aerobic formation of ACh was greatly decreased, accompanied by a marked rise of O2-uptake by the addition of 2, 4-dinitrophenol to CHA-CYP-Pyruvate system or to brain slices, while only slightly depressed with CHA-ATP-Acetate system. ACh formation in CHA-CYP-Pyruvate system was considerably accelerated by the addition of CoA, adenylic acid and cysteine, whereas slightly increased with magnesium and coenzyme 1. ACh formation in the brain tissue is likely to be enhanced by some mechanism closely related to the respiratory system, especially to the oxidative phosphorylation coupled with it.