[Clinical effect of nitrazepam on psychoneurosis with insomnia].
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Biomedical subjects
Publications and source records attributed to M Hosaka.
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Primary leiomyosarcoma of bone is very rare. Most of reported cases were osteolytic. We report a primary leiomyosarcoma arising from the neck of the femur of a 43-year-old woman who had no remarkable abnormalities on plain radiographs. Magnetic resonance imaging (MRI) clearly depicted the lesion. Biopsy revealed it leiomyosarcoma. Gynecological and gastrointestinal examinations ruled out metastatic leiomyosarcoma. Wide excision of the tumor was performed and followed by endoprosthetic replacement of the proximal femur. Microscopic examination revealed tumor cells infiltrating into the intertrabecular space.
The bactericidal activity of gatifloxacin, a new 6-fluoro-8-methoxy quinolone, was determined in a dynamic in vitro model mimicking complicated lower urinary tract infection. Strains of Pseudomonas aeruginosa and Enterococcus faecalis with different susceptibility were exposed to changing gatifloxacin concentrations, simulating human urinary concentrations afer oral treatment with 200 mg twice daily for 3 consecutive days. Bacterial numbers of P. aeruginosa (minimal inhibitory concentrations, MIC: < or =32 microg/ml) and of E. faecalis (MIC: 16 microg/ml) were reduced to undetectable levels during exposure. For the strains with lower susceptibility, gatifloxacin showed bactericidal activity, but eradication was not complete. Thus, in a complicated urinary tract infection model, breakpoint MICs of gatifloxacin for uropathogenic organisms were presumed to range from 16 to 32 microg/ml. At least 86% of recent clinical isolates of P. aeruginosa and E. faecalis were inhibited at its breakpoint MIC. These results suggest that gatifloxacin may be useful in the treatment of urinary tract infections.
The uptake and intracellular activity of fleroxacin in murine J774.1 macrophages and human polymorphonuclear leukocytes were studied. The uptake of fleroxacin by J774.1 macrophages was rapid and reversible. The cellular to extracellular concentration ratios of fleroxacin in both types of phagocytes ranged from 5 to 6. These ratios were almost equal to those of ofloxacin and ciprofloxacin, and higher than those of the beta-lactam antibiotics, flomoxef and piperacillin. The intracellular activity of fleroxacin in J774.1 macrophages, examined with Staphylococcus aurenus as a test bacterium, showed that its bactericidal action was dependent on both the extracellular concentration and the exposure time. Fleroxacin reduced the number of viable cells of ingested S. aureus at an extracellular concentration that simulated the clinical serum levels, that is, killing more than 70% of the bacteria at 4 micrograms/ml. The bactericidal activity of fleroxacin in phagocytes was superior to that of erythromycin, flomoxef and piperacillin. These results indicate that fleroxacin is taken up well by phagocytes, reaching a concentration several fold higher than the extracellular concentration, and that it has potent activity against intracellular pathogens.
We investigated whether the antitumor action of sodium 5,6-benzylidene-L-ascorbate (SBA) is mediated via oxidation-involved mechanism, in three different systems: 3'-methyl-4-dimethylaminoazobenzene (DAB)-induced rat hepatocellular carcinoma (in vivo), its homogenate (semi in vivo), and cultured cells (in vitro). Oral intake of DAB irreversibly produced hepatocellular carcinoma in rats, with a maximum incidence of carcinogenesis after 4 months. Intravenous administration of SBA induced vacuolar, eosinophilic degeneration and nuclear debris, producing greater amounts of ESR signal of ascorbate radical and hydrogen peroxide (H2O2)-derived chemiluminescence (CL) (H2O2-CL) in the cancerous tissue than in the normal tissue. When SBA was directly added to the homogenates, higher amounts of ascorbate radical and H2O2-CL were generated in cancerous tissues. When SBA was added to the RPMI1640 medium supplemented with 10% fetal bovine serum, methionine was oxidized to methionine sulfoxide and H2O2 was produced in amounts that sufficiently induce apoptotic cell death in human promyelocytic leukemic HL-60 cells. Cytotoxic activity of SBA was significantly reduced by catalase. These data suggest that antitumor activity of SBA in vivo might at least in part be due to H2O2, produced from SBA.
The role of hydrogen peroxide in the induction of cell death in human promyelocytic leukemic HL-60 cells by sodium 5,6-benzylidene-L-ascorbate (SBA) and its degradation product, ascorbic acid, was investigated. Millimolar concentrations of these compounds induced cell death, characterized by cell shrinkage, nuclear and internucleosomal DNA fragmentation, disappearance of microvilli and condensation of chromatin near the nuclear membrane. Catalase significantly reduced the cytotoxic activity of these compounds, whereas superoxide dismutase, nitric oxide (NO) generator, NO scavenger and NO synthase inhibitor were inactive, suggesting the possible role of H2O2. Determination of H2O2 with the peroxyoxalate chemiluminescence demonstrated that sodium ascorbate and SBA produced H2O2 in amounts necessary for cell death induction.
Role of hydrogen peroxide (H2O2) in the induction of antitumor activity against chemically-induced rat hepatocellular carcinoma by sodium 5,6-benzylidene-L-ascorbate (SBA) was investigated. ESR spectroscopy demonstrated that rat liver homogenate of cancerous tissue significantly enhanced the radical intensity of SBA more potently than that of precancerous or normal tissue. The peroxyoxalate chemiluminescence method demonstrated that SBA significantly enhanced the production of H2O2-derived chemiluminescence intensity in the liver homogenates, and the effect of SBA was greater in cancerous tissue than in precancerous or normal tissue. Addition of ascorbic acid, a degradation product of SBA, showed similar but slightly weaker stimulation effects. These data suggest that antitumor activity of SBA in vivo might, at least in part, be due to H2O2 production.
Millimolar concentrations of sodium ascorbate (vitamin C) induced apoptotic cell death in human promyelocytic leukemic HL-60 cells. The apoptotic cells displayed a smaller cell volume, disappearance of cell surface microvilli, appearance of cytoplasmic vacuoles, chromatin condensation, nuclear fragmentation and production of apoptotic bodies. The apoptosis-inducing activity of sodium ascorbate was significantly enhanced by noncytotoxic concentrations of CuCl2, but was almost completely eliminated by FeCl3. CuCl2 transiently stimulated the hydrogen peroxide (H2O2) production by sodium ascorbate, whereas FeCl3 slightly reduced the H2O2 production. alpha-Tocopherol (vitamin E) slightly enhanced the radical and H2O2 productions, and apoptosis induction by sodium ascorbate. The effect of alpha-tocopherol seems to be rather specific for ascorbic acid, since alpha-tocopherol did not significantly affect the cytotoxic activity of CuCl2, FeCl3 nor gallic acid. The present study demonstrated the cooperative action of vitamins C and E.