Biopharmaceutical study of the hepato-biliary transport of drugs. VII. Improvement of the bioavailability of rifampicin by dosage form design.
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Biomedical subjects
Publications and source records attributed to K Takada.
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Cytotoxicity against lymphocytes freshly transformed by EBV was studied in an autologous system by trypan blue exclusion of EBNA-positive cells and 51Cr-release assay. When EBV-tranformed lymphocytes were incubated with EBV-positive serum and autologous unfractionated lymphocytes or K-cells from sero-positive healthy donors, the transformed cells were significantly damaged. The cytotoxicity against newly produced EBNA-positive lymphocytes was also remarkable when sero-positive healthy donor lymphocytes were exposed to EBV, immediately followed by incubation with positive serum. In contrast, EBV-transformed cells incubated with autologous lymphocytes or T-cells alone were not significantly affected. EBV-positive serum alone was also not cytotoxic, regardless of inactivation. These results strongly suggest that antibody-dependent cellular cytotoxicity (ADCC) plays an important role in immunological defence against EBV oncogenesis in healthy humans. However, ADCC was not seen when immunosuppressed patients were examined.
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Twenty peptide-4-methylcoumarin amides (MCA) were newly synthesized and tested as possible substrates for alpha-thrombin, factor Xa, kallikreins, urokinase, and plasmin. These fluorogenic peptides contained arginine-MCA as the carboxyl-terminus. Release of 7-amino-4-methylcoumarin was determined fluorometrically. Of these peptides, the following were found to be specific substrates for individual enzymes: Boc-Val-Pro-Arg-MCA for alpha-thrombin, Boc-Ile-Glu-Gly-Arg-MCA, and Boc-Ser-Gly-Arg-MCA for factor Xa, Z-Phe-Arg-MCA for plasma kallikrein, Pro-Phe-Arg-MCA for pancreatic and urinary kallikreins, and glutaryl-Gly-Arg-MCA for urokinase. Moreover, these peptide-MCA substrates were resistant to plasmin.
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S-6436 and S-6437 are preparations of sustained release cefalexin, which consist of 30% of nonenteric coated granules and 70% of enteric coated ones. With oral administration of those preparations at b.i.d. regimen, good efficacies can be expected. Those preparations were orally given to 39 patients with skin and soft tissue infections and 4 patients with other infections at the dose levels of 1,000 approximately 2,000 mg/day (20 approximately 50 mg/day in children) at 2 divided doses. Excellent effect was observed in 30 patients and good effect was found in 13 patients. In 11 patients, usefulness of b.i.d. regimen was recognized. No side effects were observed. From the above. S-6436 and S-6437 are considered to be unique and useful preparations.
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Single doses of 5, 15 or 50 mg of Na3Ca-DTPA per kilogram of body weight were intraperitoneally injected 1 hour (prompt treatment) or 3 days (delayed treatment) after the intravenous injection of 144CeCl3 in the rat. The daily urinary and fecal excretion of 144Ce was determined for 15 days post 144Ce injection. The retention of 144Ce in the several organs 15 days after the 144Ce injection was also determined. A method to assess the DTPA-enhanced amount of urinary excretion of 144Ce from the early urinary excretion of 144Ce post therapy was proposed.
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Two cases of plasmacytoma in the oral cavity are described. The first case was a plasmacytoma of the palate in a 64-year-old man, which be an oral manifestation of multiple myeloma, with fatal course 17 months after the first examination. The second was a plasmacytoma in a 43-year-old man, manifesting first in the mandible. A review of the recent Japanese dental literature was made: 14 cases were found in the literature exhibiting evidence of plasmacytoma in the oral region. Eight of these patients had oral manifestations of multiple myeloma (IgG myeloma, 3; IgA myeloma, 1; IgD myeloma, 1; B-J myeloma, 1; undetermined, 2). The other six cases were single lesions of plasmacytoma. The ratio of males to females was 1:1. The mandible was more frequently involved than the other oral structures. The site of predilection was the posterior portion of swelling and, less frequently, pain. Surgical treatment was favored in single lesions of plasmacytoma, while in myeloma chemotherapy and a combination of radiotherapy-chemotherapy constituted 75% of treatment.
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