The toad's brain was succesively destroyed downwards in several parts and the effects on the posterior lymphatic heart-beat investigated. As a result it was found that the most striking effect was observed in the case of the destruction of the optic lobe and the medulla and that it was quite contrary to each other. When the central analeptics ware applied on the optic lobe, the tone of the lymphatic heart was increased and by the application of the central depressants it was decreased, but when applied on the medulla, the effects of both series of drugs were quite opposite to each other. Thus the presence of the higher centres which control the lymphatic heart-beat was suggested, the accelerating center being on the optic lobe while the inhibitory was on the medulla.
Three types of movement were observed to occur during the normal intestinal movements of a rabbit by means of a glass abdominal window. The frequency of the appearance of each type of movement is controlled by the volume of intestinal content. When a large quantity of fodder taken is moderate, the rhythmic segmentation set out more than half. While a small quantity provokes the pendular movement. The above conclusions are not only affected by the kind of fodder, but by substitutes of isotonic solutions for fodder. We could demonstrate these findings by an in vitro experiment using an excised intestine connected in a circle.
The actions of aconitine, mesaconitine and jesaconitine, each of which has been isolated by Prof. Harusada Suginome, and that of aconitine (Merck) are shown to be quite related to each other, however, jesaconitine and mesaconitine are more toxic than aconitine (Suginome and Merck). When their hydrochloride salts are dissolved in water, their characteristic toxicity becomes gradually decreased and in course of time their actions are also qualitatively changed by hydrolysis.
The hydrochloride salts of aconitine, mesaconitine, jesaconitine (all Suginome's) and aconitine (Merck) were applied to intact skin, external auditory canal, conjunctival sac, nasal or oral cavity, esophagus, stomach, small intestine, glans penis or vagina of animals in the form of watery solution, alcoholic solution, ointment or powder and it has been found that these drugs are, even in minute doses, rapidly absorbed from epithelial tissues, skin and mucous membrane of test animals.
Simultaneous studies of the gaseous exchange of the kidney, of renal blood flow, and of urinary output during the diuresis induced by intravenous injection of isotonic solution of several fatty acids, and some salts have been carried out on normal, urethanized rabbits which had been operated on by the technique of Barcroft and Brodie. The rate of blood flow through the kidney has been measured directly by a, new electrographic method. The results obtained may be summed up as follows. (1) The average renal oxygen consumption of 108 rabbits in the resting period was calculated as 0.0574 cc ± 0.0043 cc per g of kidney per min. (confidence limits, α = 0.05). By the injection of sodium chloride there was no significant change in oxygen consumption. of the kidney. In the diuresis of potassium chloride, potassium acetate or calcium chloride the oxygen consumption was increased, but contrarily in that of sodium bicarbonate, sodium carbonate or sodium acetate it was decreased. In cases of n/100-fatty acids no significant change in the oxygen consumption was found, but in cases of n/60-and n/30-fatty acids the decrease of oxygen consumption was observed. The decrease of oxygen consumption by the injection of each fatty acid was remarkable in cases Of acetic acid, and then in succession succinic acid and adipic acid, but in cases of suberic acid there was no significant decrease of the oxygen consumption. (2) The average renal carbonic acid formation of 52 rabbits in the resting period was calculated as 0.0811 cc ± 0.0104 cc per g of kidney per min.. And respiratory quotient in the kidney varied from 0.22 to 2.68 (rejection limits, α=0.05). By the injection of n/30-fatty acids the decrease of the carbonic acid formation and the respiratory quotient was occasioned. (3) The average renal blood flow of 108 rabbits in the resting period was calculated as 2.14 cc ± 0.19 cc per g of kidney per min.. By the injection of sodium salts the renal blood flaw decreased, but by that of potassium salts no significant changes of the blood flow were found. On the contrary, by injecting of calcium chloride the blood flow was increased. Fatty acid employed by author had no significant effects to the blood flow. (4) There was a remarkable increase of urinary output in cases of calcium chloride among the salts diuresis and suberic acid among the fatty acids diuresis. (5) The relation between renal blood flow and renal oxygen consumption, and that between renal blood flow and urinary output were concluded to run parallel in their variations. But no relation between. urinary output and renal oxygen consumption could be found.
Quinone monoxim methylether, synthetized by Dr. S. Hayashi, was pharmacologically examined. This compound caused. a curare-like paralysis on the frog, but on mice and rabbits it showed an unrest, which was followed by a convulsion accompanying asphyxia. Histological changes were observed chiefly in the cardio-vascular organs of the animals submitted to a large dose. The LD 50 to mice were intravenously 0.197 ± 0.01, subcutaneously 0.104 ± 0.01 (by van der Waerden method); 0.233 ± 0.11 (by Behrens-Kärber method) g/kg respectively. On the excised skeletal muscle a paralytic action was noted by the concentration higher than a certain limit, while little effect, was observed on the motor nerve-endings. The drug showed a slight hemolytic as well as a methemoglobin forming action in vitro experiments : The hemoglobin content and the leucocytes were increased, but the erythrocytes decreased when given to rabbits. In vitro and also in vivo, the drug prolonged or hastened the clotting time of the blood of the rabbits, according to the size of the dose, from which followed reliable changes in the fibrinogen and thrombin contents.
In a recent research sodium succinate has been used as an antidote against pentobarbital-intoxication, and now it is generally accepted that succinate has a remarkable diuretic action. This has promoted considerable interest for us. Including this agent, I have compared the diuretic actions of dicarboxylic acid salts in this series, that is sodium succinate, adipate and suberate while taking acetate as a standard. Japanese toads were used, throughout in this experiment for a study of diuresis. I incised skin and muscles of this animal on its back on a dry wooden board by thermocautery without anesthesia. Special cannula were inserted into the ureters on both sides, and using a Y-form tube the urine was collected into a thin glass measuring cylinder, and its amount was read every 15 minutes. With. no water-supply the urine of the animals tnus treated generally decreased slowly and rather regularly, and 2 or 3 hours later its quantity reached a level of ca. 0.1 cc in this time-interval. Using this level as a control, 0.5-1.0 cc of 1 normal solution or 4 cc of isotonic solutions these agents were injected into Vena cutanea magna. Soon after this injection the urine-flow increased in most cases, and usually after one hour more it returned to the control level; sometimes tp a lower level than before. This increased portion during this period was divided by injected solution's quantity and multiplied by 100, so I expressed the activity of the diuretic action of a certain pharmaca in percent-rate. As to the method for the investigation of the ratio of excreted substances through both glomeruli and tubules, I applied “modified Tamura's operation” on Japanese toads. The determination of the agents in toad's urine was carried out by Van Slyke and Palmer's method well known as the total organic acid estimation of urine, but I modified it slightly in details taking thymol blue as an indicator instead of phenolsulphophthalein and tropaelin 00. Increase of urine flow by the intravenous injection of 1 normal solution of acetate was 50.8%, succinate 82.9%, adipate 79.4% and suberate 132.6%. On the other hand, in case of isotonic solution, acetate was 25.9%, succinate 41.9%, adipate 28.2% and suberate 49.5%. The ratio of elimination of organic sodium salts from tubules as compared with that from glomeruli, by the intravenous injection of acetate was 4/100, succinate 14/100, adipate 17/100 and suberate 25/100. The diuretic actions of these salts were usually less effective When injected into Vena abdominalis which corresponds to the portal vein of warm-blooded and the liverless toads according to Molitor and Pick's method very often showed higher diuretic response to the organic salts than normal toads.
The body temperature of 450 normal rabbits has been measured rectally in the natural posture and it has been found that their body temperature be- came constant two hours after meals averaging 39°.26 C (δ=0°.21 C); a large number of them stand between 38°.9 and 39°.6 C. These results were almost constant in rooms where the temperature ranged from 7° to 28°C. On the other hand, the pyrogenic activity of the infected distilled water injected in the ear-vein of the rabbits was shown to be parallel to its dose amount. With repeated, injections of a certain amount of Escherichia coli filtrate rabbits do not develop tolerance against their pyrogenic reactions.
The intravenous injections of infected distilled water have been shown to develop three types of fever curves on rabbits. (1) With doses of more than 10 cc/kg the curve falls suddenly after. injection by shock. (2) With 1.25-10 cc/kg a diphasic curve appears in which the second peak is higher than the first. (3) With doses of less than 0.5 cc/kg a diphasic curve in which the first peak is. higher than the second is obtainable. If the doses injected are reduced to 0.125 cc/kg or less, one of the two peaks is extinguished and a monophasic curve established. The author has further analysed a large series of fever curves and suggested that the second peak has some meaning in the tolerance against pyrogenic reactions of the test animals.
Rhabdias bufonis which can be found plentifully in every toad intestine throughout the year, were employed in these experiments consisting in vitro and in vivo examinations. Experiment in vitro : Each group of five worms were put in drug solutions. The charges in their movement in the solution 'were recorded until the moving stopped, estimating the toxicities of the drugs to the worms. Experiment in vivo : The drugs were given toads per os. From the following day observations on the numbers of worms excreted from the toads were continued for six days. On the last day of the observations, these toads were dissected to see the pathological changes caused by diugs in the alimentary canal and other organs concerned. Twenty nine drugs were tested by this method. Some of them were effective in vitro experiment and others were effective in vivo experiment, while most popular anthelmintics were proved to be effective in both expeiments.