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Biomedical subjects

M Sakamoto

Publications and source records attributed to M Sakamoto.

At least 793 records · Page 44Linked to original sources
PubMed1983

Toxicological studies on bestatin. I. Acute toxicity test in mice, rats and dogs.

Studies on acute toxicities of bestatin (NK421) were carried out in both sexes of mice and rats, and male dogs. NK421 was administered subcutaneously, intraperitoneally and orally in mice and rats, and orally in dogs respectively. Mice and rats were observed for 14 days after treatment and LD50 values were calculated by the probit method. NK421 showed very low toxicity and no death occurred in any species following the oral administration of the maximum dose capable of dosing such as 4 g/kg for mice, 2 g/kg for rats and 1.2 g/kg for dog. General toxic signs seen in mice and rats following subcutaneous and intraperitonial injections were as follows; depression, suppressed movement, piloerection, inhibition of spontaneous movement, anorexia and emaciation. Death occurred within 5 days after administration. The toxic target organs of NK421 were found to be kidney, lymphoid tissue and liver based on histopathological examination of dead animals.

Administration, Oral↗
PubMed1983

Toxicological studies on bestatin. II. Subacute toxicity test and recovery study in beagle dogs.

Subacute toxicity and its recovery of bestatin (NK421) was studied on both sexes of 34 Beagle dogs. At dose levels of 600, 240, 96 and 38.4 mg/kg, NK421 was administered orally to dogs for 90 successive days. The control group was treated orally with 2 g/dog of corn starch. Each group was constituted of 3 males and 3 females, and 2 males and 2 females were added to the 240 mg/kg group for the recovery test for 35 days. As general symptoms, loss of appetite, vomiting, abnormal feces (loose stool, diarrhea, mucous stool), eye mucus, decoloration of the visible mucous membrance and unkempt fur were observed slightly and almost dose-dependently in the group dosed with more than 96 mg/kg. Body weight decreased with the passage of time in the 600 and 240 mg/kg groups, but no death appeared in any group. In correlation with general signs, slight anemia was seen hematologically, and the increased alkaline phosphatase activity and the decreased albumin ratio in serum protein fraction were observed biochemically. The slight abnormal findings of bone marrow, spleen and liver were also demonstrated histopathologically. All the above findings disappeared during the recovery period. The maximum non-toxic dose of NK421 in this study is estimated to be 38.4 mg/kg in dogs.

Animals↗
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

Studies on the OA-6129 group of antibiotics, new carbapenem compounds. II. In vitro evaluation.

The OA-6129 group of antibiotics, new carbapenem compounds, had relatively potent antimicrobial activities against Gram-positive and Gram-negative bacteria. Synergism of compound OA-6129A in combination with conventional beta-lactam antibiotics was observed in antimicrobial activity against beta-lactamase producers such as Proteus vulgaris GN 76 and Citrobacter freundii GN 346. The new carbapenem compounds were slightly superior to PS-5 in stability to kidney homogenates of various animal species.

Animals↗
PubMed1982

Pharmacological studies on carbapenem antibiotics. I. Metabolism of PS-5 in animal tissues.

After injection into mice and dogs, PS-5 showed a very rapid decrease in its blood concentration, compared with cefazolin. Using in vitro experiments with tissue homogenates and acetone powder preparations, the kidney was found to be the primary site of PS-5-inactivation, although the extent of the inactivation varied depending on the species of animals. The comparative stability data of PS-5, NS-5 (deacetylated PS-5), thienamycin and N-formimidoylthienamycin in kidney homogenates of mouse, rabbit, dog and man are presented. Bilateral nephrectomy and the injection of ethylenediaminetetraacetate seemed to prolong the survival time of PS-5 in rats and mice respectively.

Animals↗
PubMed1982

Pharmacological studies on carbapenem antibiotics. II. Isolation of a PS-5-inactivating factor from the rat kidney.

A factor responsible for the in vivo metabolism of PS-5 was isolated from the microsomal fraction of the rat kidney. This factor, which did not attack penicillins and cephalosporins, was enzymologically identified with particle-bound renal dipeptidase. Under the action of this factor, PS-5 was inactivated to give three products designated PS-5D I, PS-5D II and PS-5D III.

Animals↗