[Oxidation with Fremy's salt. VII. Syntheses of several 5-substituted-1-naphthols (author's transl)].
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Biomedical subjects
Publications and source records attributed to Y Harada.
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The distribution of ceftezole in blood and tissues and its excretion after intramuscular or intravenous administration of single doses of 10 and 20 mg/kg were compared with those of cefazolin, cephaloridine and cephalothin. Blood levels of ceftezole in rats and rabbits were lower than those of cefazolin, and higher than those of cephaloridine and cephalothin. Retention time of ceftezole in the blood was somewhat shorter than that of cefazolin. However, blood levels of ceftezole in dogs were nearly the same as those of cefazolin and cephaloridine. The rate of urinary excretion of ceftezole in 24-hour urine after administration in rats and rabbits was found to be higher than those of the other antibiotics tested. In dogs, however, the rate of urinary excretion of ceftezole was nearly the same as that of cefazolin and higher than those of cephaloridine and cephalothin. The biliary excretion of ceftezole in rats and dogs was much higher than those of cephaloridine and cephalothin, but lower than that of cefazolin. Tissue distribution of ceftezole in rats was compared with that of the other antibiotics by intramuscular and intravenous administration. The initial level of ceftezole in the kidneys was found to be substantially higher than those of the other antibiotics. The initial level of ceftezole in the liver and lungs was also slightly higher than those of the other drugs when administered intramuscularly. Tissue levels of ceftezole were somewhat lower than those of cefazolin in rabbits after intravenous administration. Ceftezole attained a higher maximum level in rat lymph by intramuscular administration than the other antibiotics tested. The maximum concentration of ceftezole present in the exudate in the rat inflammatory pouch was higher than that of cefazolin. In rabbits with cerebrospinal meningitis induced by infection of Streptococcus pyogenes, the level of ceftezole in the cerebrospinal fluid was several times higher than that in normal rabbits. The serum level and urinary excretion of ceftezole was examined in 6 healthy male volunteers after intramuscular administration of a single dose of 500 mg. Ceftezole attained a mean maximum serum level of 22.9 mug/ml 30 minutes after administration and disappeared from the blood in about 6 hours. It was excreted rapidly in the urine. The concentration in 1-hour urine was the highest (mean level: 2,667 mug/ml) and the total excretion rate was 92.6%. No metabolites with antimicrobial activity were observed in the urine. No changes in the pattern of plasma level and urinary excretion and no accumulation in the tissues were observed after repeated intramuscular administration of 20 mg/kg of ceftezole in rabbits, 26 times, for 14 days.
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MRMT-1 is a mammary carcinoma induced in immunologically impaired female Sprague-Dawley rats fed 3-methylcholanthrene. Its biological characteristics include transplantability to syngeneic normal rats and spontaneous metastases to various organs. Hypophysectomy performed 48 hr after tumor inoculation resulted in tumor regression accompanied by the disappearance of the metastasis in lungs of all the animals. The hypophysectomized animals were given replacement treatments, such as transplantation of pituitary homogenates, pituitary homograft underneath the renal capsule, or prolactin administration, and the inhibited tumor growth was markedly reactivated, with the reappearance of lung metastasis. These results indicate that MRMT-1 mammary carcinoma is prolactin dependent.
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In order to evaluate the efficacy of Bleomycin (BLM) against brain tumor, a study was made on the inhibitory effect of BLM on the proliferation of cells derived from 8 cases of astrocytoma and 2 cases of meningioma and the proliferation of Ehrlich ascitic, HeLa and Mouse-Foot-Pad cells of strained epithelial origin. Morphological changes induced by BLM were also observed with phase contrast microscope and scanning electron microscope. Actively growing monolayer cells were exposed to BLM whose concentration was adjusted to 0.15, 0.6, 2.5, 10, 40, 160 mug/ml in the cultivating medium for 7 days. The inhibitory effect on cellular proliferation was evaluated by calculating the number of cell nuclei. When the concentration of BLM was adjusted to 0.15 mug/ml, the inhibition of Ehrlich ascitic, HeLa and Mouse-Foot-Pad cells was greater than the control by 50%. On the contrary, a higher concentration of BLM, that is 0.6-10 mug/ml, was necessary in the case of brain cells. The latter cells appear to be generally less sensitive to BLM than the foregoing strained cells of epithelial origin. Morphological changes consisted of cytoplasmic vacuolation, shortening and narrowing of cytoplasmic processes, nucleolysis and flattening of the surface structure. These findings, however, were not confirmed to be changes specific to BLM. Lastly, a brief review of the literature and discussion were made on the methods of administration and tissue concentration of BLM.
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Induction of a spontaneously metastasizing carcinoma in rats was attempted. Four-week-old Sprague-Dawley female rats were thymectomized or/and splenectomized and fed 200 mg (20 mg times 10) of 3-methylcholanthrene from 7 weeks of age. In addition to these treatments, the early-appearing tumors were excised in order to select by isoimmunity the late-appearing ones that were less antigenic. The latter were easily transplanted into normal syngeneic female rats with metastasis to remote organs. This metastasizing capacity of the tumor became an inherent character in syngeneic normal rats from generation to generation of transplantation. With one of these tumors (MRMT-1) many cancer cells were histologically detected in circulating blood 3 days after tumor transplantation and arrested in capillary beds of lungs. The spontaneous metastasis to lymph nodes and lungs was macroscopically found within several weeks after tumor transplantation.
New antibiotics, mannopeptins A and B, were isolated from the fermented broth of Streptomyces platensis strain FS-351. Ferrous ion is essential for the antibiotic production, since no productivity was noted with media containing less than 0.11 mM ferrous ion and maximum production was achieved at a concentration of 1.8 mM. The antibiotics are basic glycopeptides with relatively high molecular weight and are similar to ristocetin and vancomycin but can be differentiated from them in view of their chemical composition and chromatographic behavior. The antibiotics were named mannopeptin after the glycopeptide containing mannose.
Mannopeptins show in vitro antimicrobial activity against gram-positive and some gram-negative bacteria. The antimicrobial activity is unaffected by the addition of serum, and potentiated by alkaline pH or decrease in inoculum size. The antibiotics exert bectericidal effect at doses twice as high as the minimum inhibitory concentration. When the antibiotics were injected into mice through either intravenous, intraperitoneal, intramuscular or subcutaneous routes, the antimicrobial activity appeared within 15 minutes in the serum of mice and was slowly excreted in the urine. However, the antibiotics were poorly absorbed by the oral route. The antibiotics were capable of protecting mice from lethal infection produced by the intravenous injection of Staphylococcus aureus, Streptococcus pyogenes and the intraperitoneal injection of Shigella sp. and Escherichia coli, but ineffective against Salmonella typhosa.
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