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Biomedical subjects

F Hirano

Publications and source records attributed to F Hirano.

41 records · Page 3Linked to original sources

[Toxicological studies on dibekacin for intravenous injection use. I. Subacute toxicity in rats and rabbits (author's transl)].

Dibekacin sulfate (DKB) dissolved in physiological saline J.P. was administered to rats intraperitoneally and rabbits intravenously for subacute 35-day toxicity test. The results were as follows: I. Wistar-strain rats (1) All the animals of both male and female died in the group with 500 mg/kg. (2) In general conditions stretching physical positions, decrease in spontaneous movements, decrease in respiration rates, unsteady steps of walking and muscular relaxation developed in the groups of high doses of either sex. The effects through the administration of this drug were also noted on the progress of body weights and food intakes in the groups of high doses. (3) In the hematological and histopathological studies, degenerative and reparative changes of tubular epithelia were evidently noted in the groups which were administered more than 100 mg/kg of DKB in both male and female. No pathological findings were noted in administration groups less than 20 mg/kg. (4) Microscopically, slight inflammatory changes were noted in the bladder of the male groups of high doses and the direct stimulative effects on the peritoneum due to intraperitoneal administration were noted but slightly in the serous membrane of the liver, spleen and the gastrointestinal tracts. (5) Judging from the above-mentioned results, "the maximal non toxic dose" through the intraperitoneal administration to rats of this drug was assumed 20 mg/kg in either sex. II. Albino rabbits (1) Neither remarkable change in the general conditions nor death was noted in each administration group. (2) The increase in the mean body weight in each group was almost similar to the control value. They consumed the amounts of food given. (3) The specific abnormal finding was not noted in the hematology and biochemical tests of serum or urine. (4) Since no change was noted on ERG in each rabbits, we estimate there is no effect to the visual organs. (5) In histopathological study, several changes revealed in some organs through the macroscopic findings, organ weights and microscopic findings but they were no more the serious changes attributable to administration. (6) We estimate "the maximal non effective dose" in this test was 10 mg/kg.

Animals↗

[Toxicological studies on dibekacin for intravenous injection use. II. Chronic toxicity in rats (author's transl)].

The toxic effects of dibekacin sulfate (DKB) in male and female rats were examined in chronic toxicity test (intraperitoneal injection), and the following results were obtained. 1) No death was noted in both male and female. 2) In general conditions, the excretion of soft or diarrheal stool was noted in groups of more than 20 mg/kg of either sex. The mean body weight was less than the control during a certain period in the male group of 40 mg/kg and in the female group of 20 mg/kg. But, in the food intakes, no particular change was noted in each group of either sex. 3) In the auricle reflex, no abnormality was noted in each group of either sex. 4) In the hematological test, the findings such as an increase of BUN, anemia, etc. were noted in the groups more than 10 mg/kg of male and more than 20 mg/kg of female. 5) In the histopathological study, evident degenerative changes of renal tubular epithelia were noted in the groups which were administered more than 20 mg/kg of DKB in both male and female, but no evident pathological findings due to the renal failure were noted in the groups of less than 10 mg/kg. Several slight changes of the thyroid gland noted in a few rats of DKB administration group of both male and female seemed to be artifact, and inflammatory changes owing to intraperitoneal injection were occasionally noted in the peritoneum of DKB injected animals. 6) Considering the above results, "the maximal non effective dose" was estimated to be 10 mg/kg in both male and female.

Animals↗

Evaluation of the mutagenicity of aminoglycoside antibiotics in Salmonella typhimurium and Saccharomyces cerevisiae.

The mutagenicity of aminoglycoside antibiotics (KM, AKM, DKB, RSM, AMK, GM, TOB) has been studied in cells of the bacteria Salmonella typhimurium and in the yeast Saccharomyces cerevisiae. The bacterial strains (Ames') monitor reverse mutation (point mutation) and the yeast strain D5 monitors mitotic crossing-over, mitotic gene conversion and point mutation. None of these antibiotics demonstrated any mutagenic activities in either the bacteria or the yeast.

Aminoglycosides↗

The inhibitory effect of bisphosphonates on glucocorticoid-induced RANKL expression in human cells.

OBJECTIVE: RANKL is known to play an important role in activating osteoclasts and advancing the progress of osteoporosis. However, little is known about the effect of bisphosphonates on glucocorticoid-induced RANKL expression in human cells. Our study was intended to clarify effects of bisphosphonates on glucocorticoid-induced RANKL expression in human cells. METHODS: Human T lymphoblastic cell line Jurkat and human osteosarcoma cell line MG-63 were used for the following experiments. RANKL expression in two cell lines was measured using reverse transcription polymerase chain reaction (RT-PCR) analysis and enzyme immunoassay (EIA). Luciferase assays using pGRE-Luc were also performed. RESULTS: In Jurkat and MG-63 cells, dexamethasone induced expression of soluble RANKL (sRANKL) protein in supernatants and RANKL mRNA in cells. Moreover, bisphosphonates, but not cyclooxygenase inhibitors, repressed dexamethasone-induced sRANKL protein production. By contrast, glucocorticoid receptor-driven transcriptional activity was not inhibited by bisphosphonates. CONCLUSION: Glucocorticoid induced RANKL expression in human cells derived from T lymphocytes and osteoblasts. Bisphosphonates inhibited glucocorticoid-induced RANKL expression, suggesting that these effects might be a new therapeutic mechanism for bisphosphonates.

Anti-Inflammatory Agents↗

Modification of T-lymphocyte subsets in peripheral blood, the liver, and the spleen during liver regeneration after partial hepatectomy of mice.

Flow cytometry analysis was performed to investigate the modifications to the T lymphocytes in peripheral blood, the spleen, and two intrahepatic lymphocyte fractions--the intrahepatic lymphocyte fraction 1 (IHL Fr.1), which is easily washed out from the liver by perfusion of collagenase solution, and the intrahepatic lymphocyte fraction 2 (IHL Fr.2), which remains in the liver after the perfusion--occurring in the liver regeneration process after partial hepatectomy of mice. The following findings were obtained: 1) The nontreated murine liver contains Thy 1.2+ cells, alpha beta TCR+ cells, gamma delta TCR+ cells, CD4+ cells, and CD8+ cells. 2) The percentage of each T-cell subset in IHL Fr.1 shows an intermediate value between that in the peripheral blood lymphocytes (PBL) and that in the IHL Fr.2. 3) One day after partial hepatectomy, the Thy 1.2+ cells, alpha beta TCR+ whole cells, and CD4+ cells in IHL Fr.2 all showed a transient, yet significant, decrease, but did not reveal any major change in the other fractions. 4) Both the alpha beta TCR dull+ cells and the CD8+ cells showed practically no change after partial hepatectomy in any of the fractions. This indicates that the alpha beta TCR dull+ cell/alpha beta TCR+ whole cell and the CD8+ cell/CD4+ cell ratios show a significant increase 1 day after partial hepatectomy only in the IHL Fr.2. Double-positive cells, which were scarcely found in the spleen of nontreated mice, appeared in the spleen after partial hepatectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗