As reported in a previous paper1) , effect of dihydrostreptomycin or chloramphenicol on α-ketoglutarate-fermentation of glucose by a growing culture of E. coli or P. fluorescens was investigated, and some evidences were provided that both dihydrostreptomycin and chloramphenicol inhibited this fermentation and that dihydrostreptomycin revealed a remarkable accelerating effect on decomposition of α-ketoglutarate.
Koepsell et al.2,3) suggested that pyruvate might be an intermediate m the formation of α-ketoglutarate from 2-ketogluconate by P. fluorescens. Katagiri, Tochikura and Imai4,5,6,7,8,9) investigated the oxidative degradation of glucose, pyruvate and members of tricarboxylic acid cycle by coli-aerogenes bacteria and confirmed that the major production of α-ketoglutarate from various carbon compounds (i. e., glucose, pyruvate, lactate, dibasic acids) by the bacteria of coli-aerogenes group did not proceed by way of the conventional tricarboxylic acid cycle, but by certain reactions in which pyruvate and acetate were concerned.
In the present paper, experiments were at first designed to study the effects of various antibiotics on the aerobic metabolism of glucose and organic acids with E. coli, that is, whether the yield of α-ketoglutarate from various carbon compounds would be affected in presence of antibiotics, and whether the effects of antibiotics upon the aerobic metabolism of these bacteria would be various among different antibiotics. Subsequently, effects of antibiotics on decomposition of α-ketoglutarate were investigated.
In the previous investigations1),2) on the effect of various antibiotics upon the aerobic carbohydrate metabolism of E. coli or P. fluorescens, it was observed that dihydrostreptomycin greatly diminished the yield of α-ketoglutarate from various carbon compounds without causing any inhibiting effect on oxidation of substrates and furthermore only antibiotically active derivatives of streptomycin produced a remarkable accelerating effect on oxidative decomposition of α-ketoglutarate.
Considerable informations have been presented on the inhibitory actions of streptomycin on bacterial oxidation of a number of amino acids and of intermediates in carbohydrate metabolism. Among discussions regarding to the mechanism of the inhibiting action of streptomycin, forcefully advanced suggestion was proposed by Umbreit and his coworkers3),4),5), who supposed that streptomycin would inhibit the condensation of pyruvate and oxalacetate to a seven-carbon compound which could not operate through the citrate shunt. Many investigators6),7),8),9),10) showed that streptomycin also interfered anaerobic metabolism of pyruvate.
In the present paper, effects of dihydrostreptomycin on the anaerobic metabolism of pyruvate (or glucose) were examined with a strain of E. coli which revealed a strong activity of α-ketoglutarate-formation from pyruvate (or glucose) under aerobic conditions.
Melanomycin is an antibiotic isolated from Streptomyces melanogenes by the present authors in 19471). This substance is a dark brown, melanin-like polypeptide. It has antitumor activity but very slight antibacterial activity. This paper is reporting the results of an experimental treatment of Ehrlich carcinoma with melanomycin.
It is well known that kanamycin has a remarkable effect on Mycobacteria, in vitro and in vivo. However, its toxicity similar to streptomycin may become a target of criticism in the course of prolonged administration tn tuberculosis practice. Therefore, lowering of its toxicity with the same or higher activity is very desirable.
Recently, H. Umezawa et al. reported the biological characteristics of new derivatives of kanamycin prepared by S. Umezawa et al. These were named tetrasodium-kanamycin-tetra-N-methanesulfonate (KMD-1) and disodium-kanamycin-di-N-methanesulfonate sulfate (KMD-3), respectively, and have been confirmed on their lower toxicity to laboratory animals than the kanamycin1,2).
In the present paper, observations on the bacteriostatic activities in vitro against human type tubercle bacilli, H2 strain and therapeutic effect on mice tuberculosis of these derivatives were reported.
Heat destruction of chlortetracycline (CTC) absorbed in fish or fish products has been studied by Tarr et al.1) and Tomiyama et al.2,3,4) It was described that cooking is the most effective means for destroying CTC in fish or fish products. Similar work on oxytetracycline (OTC) was carried out by Malaspina6). It may be, however, difficult to reproduce these experimental results, since pH, penetration of the antibiotics or heat, and many other chemical and physical factors may be dependent upon the fish material used.
In order to provide more fundamental knowledge concerning decomposition of the antibiotics, basic experiments were carried out, in which effects of temperature, pH, and some additives upon decomposition of OTC and CTC were investigated.
Most fresh cavities in pulmonary tuberculosis are curable by the double or triple combined chemotherapy with isoniazid and PAS or with streptomycin, isoniazid and PAS. Management of the chronic, active, treatment-failure case with tubercle bacilli resistant to multiple drugs continues to be a major problem in tuberculosis hospitals. Disappointing results have attended the trials of many secondary drug regimens. A high rate of sputum “conversion” was obtained by the treatment of such case with the quintuple combined chemotherapy with streptomycin, isoniazid, PAS, cycloserine, and kanamycin, although double or triple chemotherapies remained ineffective for such case. The success of sputum converison was observed in patients whose tubercle bacilli remained resistant to either of two drugs, streptomycin or isoniazid, and not in those whose tubercle bacilli were resistant to both the drugs or more.
An amazing therapeutic effect of oral griseofulvin in the treatment of dermatomycoses was reported by a number of investigators. The present paper deals with the clinical results obtained by the author in treating tinea cruris, tinea corporis, tinea pedis and onychomycosis with oral griseofulvin. A special reference is made to the dosage for onychomycosis.
Griseofulvin is a metabolic product of Penicillium griseofulvum Dierckx isolated by Oxford, Raistrik and Simonart1) in 1939. Its antifungal activity was recognized since early time, and it was chiefly used in the agricultural field. In was also found that griseofulvin displayed a systemic antifungal activity when it was applied as a preventive drug for Botrytis infection of lettus and Alternaria disease of tomato.
In 1958, Gentles2) noticed that griseofulvin has a distinct therapeutic effect when it is given orally, 60 mg/kg per day consecutively, to guinea pigs infected experimentally with Microsporum canis. About that time, Lauder and O’Sullivan3) obtained a similar result in cattle infected naturally with Trichophyton rubrum. Since that, griseofulvin became abruptly the object of dermatologists’ attention as a therapeutic for trichophytoses.
Williams, Marten and Sarkaney4) firstly in 1958 treated human ringworm patients with griseofulvin. According to their report, 7 cases of ringworm due to Trichophyton rubrum were cured within 2–3 ·weeks by the consecutive oral administration of griseofulvin, 2.0 g daily. The effectiveness of oral griseofulvin in human patients was also proved by Riehl5), and Blank and Roth6). The present authors have tested the clinical effect of griseofulvin in the treatment of ringworm. The results are described in the present paper.
Trichophytosis of the skin is one of the most common diseases of outpatients encountered, and various external remedies have been tried for its treatment. In spite of proper use of these remedies, however recurrence as a result of incomplete cure, development of dermatitis caused by irritation of the remedy used, and unsuccessful topical treatment because of deep-seated lesion have been observed in many cases. Therefore, clinicians are anxious for the appearance of oral remedy, difinitely effective and without the above mentioned defects.
Griseofulvin, an antibiotic firstly isolated from Penicilliurn griseofulvurn Dierckx by Rainstrick, Simonart and Oxford, in 1939, is just the remedy that meets those demand. The recent reports from Europe and the United States described the favorable effects of griseofulvin in both experimental and clinical dermatomycoses. The authors recently had a chance to try griseofulvin tablets for clinical dermatomycosis, being supplied with samples by the courtesy of Glaxo Laboratories Ltd. and Shin Nihon Jitsugyo Co. Ltd. Although the term of observation is short to draw final conclusion, the results obtained to this day are presented here.
Griseofulvin is an antibiotic first isolated by 0xford, Raistick and Simonart.1) Its chemical structure was clarified by Grove, MacMillan, Mulholland and Rogers.2) Formerly this substance was applied as a curative agent for fungus diseases in plants,3) but in 1958 Gentles4) proved its effectiveness in experimental ringworm of guinea pigs when given orally. This investigation led its usage for dermatomycoses in man and a number of cases have been reported5–9) since then.
In this paper are reported the results obtained m 29 cases of clermatomycosis treated with griseofulvin.
It is an important problem to be solved that trichophytia superficialis should be treated principally with oral griseofulvin or could be treated sucessfully with routine topical ointment. The authors are of opinion that there is a posibility to cure simple trichophytia superficialis by applying ointments several times a day for the same period, aat least 30–50 days in average, as in griseofulvin oral treatment. In the International Symposium on Griseofulvin held in Miami, U.S.A., last year, Castello reported satisfactory results with oral griseofulvin combined with topical treatment. Thus, clinicians are anxious for potent ointments well adapted for topical treatment.
The present authors have tried to use variotin, an antifungal antibiotic discovered in Institute of Applied Microbiology, University of Tokyo, as an ointment. This antitrichophytic antibiotic in solution has been sold and confirmed to be effective by a number of investigators. However, application of variotin solution is somewhat limitted because it is a tincture not to be applied on erosious surface, and it causes severe smarts when applied to inguen.
In order to obtain an ointment that can be applied to any lesions freely and does not cause smart or irritative symptoms, experiments were carried out on ointment bases, stability of variotin and clinical effects. The fundamental studies on variotin ointment and favorable clinical experiments using selected ointments are presented in this paper.