Yoshito Kobayashi

PYROGEN-PRODUCING MOLDS AND OTHER MICROBES EXISTING IN GLUCOSE-POWDER

Up to the earlier period of the war, undesirable reactions such as fever, chills, headache, general lassitude or fluctuation of white cell count following the intravenous injection of hypertonic or isotonic glucose-solutions were not so frequently witnessed. Consequently, these clinical reactions hardly presented any problem from the practical standpoint. Towards the end of the war, many commercial products of low quality were in wide circulation, some of which were revealed to be of substandard qualifications according to bacteriological or other routine investigative tests described in existing pharmacopoeia (J.P.V.). Thus we concede the fact that the flooding of those evidently inferior products in postwar markets is without doubt a factor which made worse the undesirable conditions of the therapeutic solution of glucose. Yet we could not ignore the fact that the officinal products which were apparently perfect and actually made to comform to the pharmacopoeial requirements occasionally yielded febrile reactions. As our animal, chemical and bacteriological examinations will show in detail in the next report, a high percentage of these apparently normal products in question contained pyrogens, it was detected, and we were convinced of the great role of “ pyrogens ” as the cause of thermal reactions in postwar Japan. Apart from the Billroths experiment in 1865 as to the cause of febrile reaction due to the intravenous injection of distilled water, experiments by Wechselmann(1), Hort and Penfold(2)in 1911, Seibert(3)in 1923, Bourne and Seibert(4)in 1925, Rademaker(5) in 1930 and Co Tui and Schrift(6) in 1942 have disclosed the fact that some kinds of bacteria could produce pyrogenetic substances, the chemical and biological properties of which became clear to some extent through their efforts along with the recent research of Robinson and Flusser(7) in 1944. Co Tui and Schrift(6) have suggested the probability of pyrogenetic reaction due to mold contamination, but Wylie and Todd(8) in 1948 reported that only bacteria were capable of producing pyrogens. Until after our preliminary report(9) on pyrogen-producing molds in 1948 no scientific news was available as for pyrogens and molds. Of late it was a great joy to know about above mentioned researches by American and English scholars and especially the report on pyrogen-producing molds by Harkness, Loving and Hodges(10) in 1950. As our through bacteriological examinations failed to detect directly any microbe in most of the pyrogenous glucose-solution sealed in ampullae, we have been left in the dark as to whether the pyrogan which was found in the solutions in ampullae has any causal dependence to microbes or not. This is the reason why we have decided to concentrate on glucose powders as the second step in our present research. Several years ago we successfully isolated a certain pyrogenous mold at our pharmacological institute but lost it when Professor Miyakes mycological laboratory was bombed in 1944. But, the memory of this first discovery revived our hopes in the postwar period and hence, in the present attempt to detect pyrogens and their origin, our main attention was naturally turned to molds rather than bacteria.

Effect of the salts of meso-oxalic acid on alloxan diabetes mellitus.

Since the discovery of insulin, various new compounds having hypoglycemic action other than the pancreatic hormone have been reported. In 1922 Collip (1) reported Glucokinin and in 1927 Allen (2) Myrtillin, both of which are extracted from plants or yeast, and have hypoglycemic action. Best and Scott (1923) (3) stated that there are substances in the thyroid gland, liver and muscles that act in much the same way as insulin. Synthalin, a derivative of guanidin is effective but not in practical use, because of its marked side-action. That a kind of fatty acid containing seventeen C-atoms is effective against diabetes mellitus was reported by Kahn (1923) (4), but there was little evidence to support it. In 1945 Nath (6) reported he had succeeded in decreasing the acetone bodies in the blood of diabetics by using amellin. In Japan, proof has been found that there are substances which have hypogly-cemic action in seaweed, yeast and certain wild plants, but their chemical composition is totally unknown. In 1948 Kumagaya (5) reported he had discovered an acidic substance extracted from the Lathyrus Palustris L. var. Macranthus (white) Fernald and effective against diabetes mellitus. These findings so far reported led us to explore some unknown acidic compounds probably contained in plants, which might be efficacious in producing a marked decrease in the blood sugar level. This report deals with the hypoglycemic effect produced by the salts of meso-oxalic acid on the rabbit and dog having alloxap diabetes mellitus (10-18).

Mechanism of anti-diabetic activity of the mesoxalates

先に我々はAlloxan糖尿病家兎及び犬にメゾ蓚酸カルシウム又はナトリウムを經口投與して糖尿の減少又は消失, 高い空腹時血糖の低下, 血中アセトン體の減少, 及び尿中の非蛋白性窒素の排泄減少を來す事實, 又この際膵臓全摘出犬に對しては作用の無い事も合わせ報告した.この事實はAllonan糖尿病動物に對するメゾ蓚酸鹽の影響は膵臓自體の機能と密接な關係あるを思わしめるものである.こゝにこの藥物の作用機轉を追求する爲に行われた實験の一部を報告する.

The toxicity of the mesoxalates and histological observations after continuous administration

メゾ蓚酸鹽の持つている抗糖尿病作用の機序に關する實験成續は, 前報に報告した通りであい.正常家兎及びラツテに就てメゾ蓚酸カルシウムの毒性を檢べ, 併せて長期間連續藥物を投與した動物の各主要験器を組織學的に檢索した結果をこゝに報告する.

Locomotion of Ascaris suilla et lumbricoides and the influence of anthelminthics upon them.

At the present time, ascariasis is to be considered as one of the serious medical problems in the oriental countries including Japan. In many human experiments in our country, it is found that both santonin and hexylresorcinol are reliable in their anthelminthic action (1). From the result of comparable studies on the pharmacological as well as clinical benefits of both drugs, it is confirmed that santonin is markedly superior to the other in view of its negligible side action. Effective doses of santonin never induce ill effects except a slight and temporary disturbance in vision, while oral administration of hexylresorcinol induced some local irritations on the mucous membrane of the digestive organ, even when it was administered under a perfect condition of coating on it. After taking santonin, ascaris are expelled alive and active. Some authorities, therefore, assume that santonin is not directly toxic to the parasites, but that rather they are irritated by the drug and migrate from the small intestine to the colon to be expelled (2-6). According to others, the drug is excreted in the intestine as an unknown compound, possibly an oxidation product, on which the ascaricidal properties may depend (7-12). But there has been no positive evidence to support both of the views until recently. We have now been able to find out a characteristic locomotion of ascaris in a glass tube which is made to imitate the shape of the bowel, and have good reasons to connect this movement of the worm closely with the anthelminthic activity of santonin (13).