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Biomedical subjects

M Tsubosaki

Publications and source records attributed to M Tsubosaki.

11 recordsLinked to original sources
PubMed1983

Toxicological studies on bestatin. IV. Studies on antigenicity, ocular mucosal irritation and mutagenicity.

The antigenicity, local irritation and mutagenicity tests of bestatin (NK421) were carried out as special toxicity studies. The antigenicity tests in rabbits and guinea pigs were as follows: active and passive anaphylactic shock tests, Schultz-Dale reaction test, PCA (passive cutaneous anaphylaxis) reaction test, agar gel precipitation test, hemagglutination test of tannic acid-treated erythrocyte and the test according to the appraisal in the U.S.A. The ocular mucosal irritation test in rabbits was performed as a local irritation test. The mutagenicity test was made using S. typhimurium TA100, TA98 strains by means of preincubation method. The results were that NK421 had no antigenicity, irritation on the ocular mucosa and mutagenicity.

Animals↗
PubMed1982

[Antitumor activity and toxicity of the degradation products and the aquated species of cis-dichlorodiammineplatinum (II)].

Antitumor activity and mouse acute toxicity of the following degradation products and aquated species of cis-dichlorodiammineplatinum(II) (CDDP): trans-dichlorodiammineplatinum(II), trichloroamminepltinate(II), tetrachloroplatinate(II), produced by heat treatment of the saline solution of CDDP, mono- and di-aquocomplexes, hydroxo-bridged dimer and trimer of CDDP, have been studied. These degradation products did not show antitumor activity against mouse leukemia L1210 corresponding to their low anti-HeLa cell activity. Their acute toxicities were much milder than CDDP. On the other hand, all the aquated species possessed higher toxicities than CDDP. Among them, the dimer and trimer were less active against HeLa cells than CDDP, and did not show antitumor activity against L1210 leukemia. However, the mono- and di-aquo complexes showed about 2 approximately 4 times higher anti-HeLa cell activity and prolonged the survival time of mice bearing L1210 leukemia similarly to CDDP.

Animals↗
PubMed1979

[Toxicological studies on pepleomycin sulfate (NK631). VI. Chronic toxicity of pepleomycin in dogs (author's transl)].

Chronic toxicity and its recovery of pepleomycin sulfate was studied in both sexes of beagle dogs. At dose levels of 0.3, 0.15 and 0.075 mg/kg, pepleomycin was administered intramuscularly to dogs for 180 successive days. Two dogs of the 0.15 mg/kg dose group were used for recovery test for 35 days. As general findings, the decrease of food intake, the loss of body weight, ulceration of foot pad, nail root necrosis and onychoptosis, ulcer of tongue and labia, and alopecia, dermatitis and necrosis at friction sites were observed more severely in the 0.3 mg/kg dose group of both sexes, especially in male, than those in bleomycin were. In the dose groups of 0.15 and 0.075 mg/kg, their findings were observed as slightly as those in bleomycin were. The death occurred in the 0.3 mg/kg dose group of both sexes. The lesions of liver and kidney were recognized in the 0.3 mg/kg dose group of both sexes, severely in male, on histopathological findings. Additionally severe fibrosis of lung was observed in one of the 0.3 mg/kg dose group of female. In general chronic toxicity of pepleomycin was revealed more severely in the 0.3 mg/kg dose group than that of bleomycin was, but in the dose groups of 0.15 and 0.075 mg/kg difference between their toxicities was not significant. In addition, chronic toxicity of pepleomycin in dogs showed more severely in male and its recovery was hardly recognized during its period. The maximum safety dose in this studies was estimated to be between 0.075 and 0.15 mg/kg in dogs.

Animals↗
PubMed1978

[Toxicological studies on pepleomycin sulfate (NK 631). I. Acute toxicity of pepleomycin in mice, rats and dogs (author's transl)].

Studies on acute toxicities of pepleomycin sulfate were carried out in both sexes of mice and rats, comparing with bleomycin, and male dogs. Pepleomycin was administered subcutaneously, intravenously and intraperitoneally in both sexes of mice and rats, and intravenously in male dogs respectively. Mice and rats, and intravenously in male dogs respectively. Mice and rats were observed respectively for 10 and 14 days after the administration. LD50 values were calculated by the method of Litchifield & Wilcoxon. LD50 values of pepleomycin were 4 approximately 6 times smaller than those of bleomycin in all routes of mice, but difference between them was not significant in all routes of rats. Additionally sex-difference of LD50 values was scacely recognized in all routes of both species. Toxicological findings observed in common to all routes of both species were ataxia, depression, tremor and epiphora, and only in all routes of mice, head-twitch, running-round and rolling were especially recognized as toxic behavior, which were not observed in bleomycin. Hepatic and renal lesions were recognized in biochemically and histopathologically in the survived rats. The dogs treated with pepleomycin 50 and 30 mg/kg had the decrease in food intake and the loss of body weight. They became moribund in 9 approximately 36 days after administration. In these dogs the lesions of liver and kidney were severely recognized in biochemical and histopathological findings. One of them which received 50 mg/kg recovered biochemically and histopathologically in 209 days after administration by the supplemental nutrition in early stage.

Animals↗
PubMed1978

[Toxicological studies on pepleomycin sulfate (NK 631) II. Subacute toxicity of pepleomycin sulfate in rats (author's transl)].

Studies on subactute toxicity and its recovery of pepleomycin sulfate (NK631) were carried out in both sexes of rats. NK 631 was administered intraperitoneally in dose levels of 0.3, 0.9, 2.7. 8.1 and 24.3 mg/kg/day for 30 days. After finishing administration of NK 631 for 30 days, 5 animals of each group were proceeded to recovery test for 35 days. During the course of the experiment, the body weight gains were suppressed in all dose levels except in 0.3 mg/kg group of male rats. The deaths were found in the animals treated with doses over 24.3 mg/kg during treatment period and in those over 2.7 mg/kg during recovery period. In biochemical and urinary analysis, the increases of serum GPT, BUN, Mg, Ca and urine glucose were moderately recognized in 8.1 mg/kg group. Additionally, in macroscopical and histopathological findings, bone damage was found in the animals treated with doses over 2.7 mg/kg during treatment and recovery periods. From these results, the maximum safety dose of NK 631 in subacute toxicity using rats were estimated to be about 0.3 mg/kg.

Animals↗
PubMed1978

[Toxicological studies on pepleomycin sulfate (NK631). III. Subacute toxicity of pepleomycin in dogs (author's transl)].

Subacute toxicity and its recovery of pepleomycin sulfate was studied in both sexes of beagle dogs. At dose levels of 2.4, 1.2 and 0.6 mg/kg, pepleomycin was administered intramuscularly to dogs for 30 successive days. Two dogs of the 1.2 mg/kg dose group were used for recovery test for 35 days. As general symptoms, the decrease of food intake, the loss of body weight, ulceration of foot pad, nail root necrosis and onychoptosic, ulcer of tongue and labia, and alopecia, dermatitis and necrosis at friction sites were observed the more severely in high dose groups, as those in bleomycin were. The death occurred in the 2.4 mg/kg dose group of both sexes. The lesions of liver and kidney were recognized in the 2.4 and 1.2 mg/kg dose groups of both sexes on biochemical, histopathological or urinary findings. Additionally slight fibrous change of lung was observed in all dose groups. Generally subacute toxicity of pepleomycin was revealed approximately in the same as or in a little stronger degree than that of bleomycin, and its recovery was hardly recognized during its period. The maximum safety dose in this studies is estimated to be between 0.3 and 0.6 mg/kg in dogs.

Animals↗
PubMed1978

[Toxicological studies on pepleomycin sulfate (NK631), IV. Chronic toxicity of pepleomycin sulfate in rats (author's transl)].

Studies on chronic toxicity and its recovery of pepleomycin sulfate (NK 631) were carried out in both sexes of rats. NK 631 was administered intraperitoneally in dose levels of 0.15, 0.3, 0.6, 1.2 and 2.4 mg/kg/day for 180 days. After finishing administration of NK 631 for 180 days, animals of each group were proceeded for 35 days recovery test. During the course of the experiment, the body weight gains were suppressed in all dose levels except for 0.15 mg/kg group of female. The deaths were found in all dose levels except for 0.15 mg/kg level of male during treatment and recovery periods. In biochemical and urinary findings, the increase of serum BUN, Mg, inorganic P. and urine glucose were slightly recognized in the animals treated with doses over 0.6 mg/kg. Additionally, in macroscopical and histopathological findings, bone damage and renal lesions were found in the animals treated with doses over 0.6 mg/kg during treatment and recovery periods. From these results, the maximum safety dose of NK 631 in chronic toxicity study using rats were estimated to be at less than 0.15 mg/kg.

Animals↗