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Biomedical subjects

Y Imamura

Publications and source records attributed to Y Imamura.

At least 307 records · Page 17Linked to original sources
PubMed1989

Stereoselective reduction of acetohexamide in cytosol of rabbit liver.

The stereoselective reduction of acetohexamide, an oral antidiabetic drug, was studied by using the cytosol of rabbit liver. A major metabolite of acetohexamide was isolated in 41.5% yield from the enzyme reaction mixture, and identified as (-)-hydroxyhexamide by techniques including the melting point, thin-layer chromatography, infrared spectrometry and optical rotation. The enantiomeric purity of (-)-hydroxyhexamide was determined on the basis of the proton nuclear magnetic resonance (400 MHz) spectrum of ester (diasteromer) derived by the reaction of (-)-hydroxyhexamide with (R)-(+)-alpha-methoxy-alpha-trifluoromethylphenylacetyl chloride. The (-)-hydroxyhexamide isolated from the enzyme reaction mixture was almost 100% in that enantiomeric form. The metabolic reduction of acetohexamide in the cytosol of rabbit liver appeared to be catalyzed by some enzymes with the same stereoselectivity.

Acetohexamide↗
PubMed1989

Effect of pH and small inorganic ions on binding of sulfadimethoxine and sulfaphenazole to human serum albumin measured by circular dichroism.

The binding of sulfadimethoxine and sulfaphenazole to human serum albumin (HSA) has been shown by circular dichroism measurements to be dependent on the N-B transition. The secondary drug binding sites were found to be optically active in the B conformation form in HSA but optically inactive in the N form. Moreover, the drug-HSA interaction in Tris-HCl buffer seems to be more sensitive to the conformational change in HSA, compared with that in the phosphate buffer.

Circular Dichroism↗
PubMed1989

Further studies on reductive metabolism of acetohexamide in heart.

Species and sex differences of acetohexamide reductase activity were investigated using the cytosolic fraction of heart homogenate. The activity in the rabbit was considerably higher than that in the other species (guinea pig, hamster, rat and mouse). No sex difference of the activity was observed in any of the species tested. Ketone-containing drugs (daunorubicin, befunolol and levobunolol) other than acetohexamide were little reduced in the cytosol of rabbit heart. Some aldehyde reductase inhibitors (phenobarbital, valproate and chlorothiazide) were found to decrease the acetohexamide reductase activity in the cytosol of rabbit heart.

Acetohexamide↗
PubMed1989

Purification and characterization of befunolol reductase from rabbit liver.

An enzyme (befunolol reductase) which catalyzes the reduction of befunolol to dihydrobefunolol was purified from the cytosolic fraction of rabbit liver to homogeneity by various chromatographic techniques. Befunolol reductase had molecular weights of 29000 on sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis and 34000 on gel filtration. The enzyme required reduced nicotinamide adenine dinucleotide phosphate (NADPH) as a cofactor and showed an optimal pH of 6.5. The apparent Km and Vmax values of the enzyme for the reduction of befunolol were 1.7 mM and 4.4 units/mg, respectively. Flavonoids, sulfhydryl reagents, heavy metals and coumarins strongly inhibited the enzyme. The enzyme catalyzed the reduction of a variety of aromatic ketones. In addition to befunolol, some ketone-containing drugs such as daunorubicin and levobunolol were efficiently reduced by the enzyme. On the basis of substrate specificities for steroids, befunolol reductase purified from the cytosolic fraction of rabbit liver appeared to be a 3 alpha-hydroxysteroid dehydrogenase.

Alcohol Oxidoreductases↗
PubMed1989

Characterization of binding sites for sulfadimethoxine and its major metabolite, N4-acetylsulfadimethoxine, on human and rabbit serum albumin.

In order to gain an understanding of protein binding of sulfadimethoxine (SDM) and its major metabolite, N4-acetylsulfadimethoxine (N4-AcSDM), the binding of SDM and N4-AcSDM to human and rabbit serum albumin (HSA and RSA) was investigated using circular dichroism (CD), fluorescence and dialysis techniques. The CD spectral characteristics of the compounds bound to the albumins suggested that the drug-binding sites on the HSA and RSA had somewhat different asymmetries. The binding constants for SDM-HSA and -RSA interaction were smaller than those for N4-AcSDM. Two specific drug-binding sites were found on RSA, similarly to HSA, from the results of competitive displacement using fluorescence probes. Moreover, SDM and N4-AcSDM were found to share the same first binding site on the albumins. It can be presumed from the displacement data with a series of p-aminobenzoates that the characteristics of the binding sites (such as depth and width of the hydrophobic cleft) for SDM and N4-AcSDM on RSA may be almost the same, but the characteristics of these drug-binding sites on HSA may be somewhat different.

Animals↗
PubMed1989

[Dissolution and absorption behavior of meclizine dihydrochloride from soft gelatin capsules].

Two kinds of soft gelatin capsules containing meclizine dihydrochloride (MZ) were prepared by using a medium-chain length triglyceride as a base. One is a self-emulsifying type, and the other is an oil dispersing type. The release of MZ from soft capsules and its in vivo absorption behavior were examined and compared with those of a commercial tablet. The release of MZ from the self-emulsifying soft capsule which was only slightly affected by pH was greater than those from the oil dispersing soft capsule and commercial tablet. The serum levels of MZ after the administration of preparations orally to beagle dogs increased in the order of self-emulsifying soft capsule, commercial tablet, oil dispersing soft capsule. This result suggests that the self-emulsifying soft capsule is useful for the increase of the bioavailability of the drug.

Administration, Oral↗
PubMed1989

[Displacing effect of serum protein binding on intestinal absorption of sulfadimethoxine].

The displacing effect of serum protein binding on the intestinal absorption of sulfadimethoxine (SDM) in rabbits was examined by using N4-acetylsulfadimethoxine (N4-AcSDM), a major metabolite of SDM, as a displacing drug. N4-AcSDM markedly decreased the in vitro serum protein binding of SDM, while many drugs including phenylbutazone and salicylic acid did not display such a marked decreasing-effect. The intravenous administration of N4-AcSDM clearly decreased the in situ intestinal absorption of SDM. As expected, the intravenously administered N4-AcSDM enhanced the serum concentration of unbound SDM in the common jejunal vein. However, the intravenously administered N4-AcSDM caused no change in the transfer of SDM across the intestinal membrane. These results indicate that the displacement of serum protein binding can become one of factors decreasing the intestinal absorption of SDM.

Animals↗
PubMed1989

[Differential effect of sodium bicarbonate on disposition of sulfadimethoxine and sulfisoxazole in rabbits].

The orally co-administered sodium bicarbonate significantly enhanced the blood concentration of sulfadimethoxine at the early stage after oral administration to rabbits, by increasing its intestinal absorption. On the other hand, the sodium bicarbonate significantly reduced the blood concentration of sulfisoxazole at the elimination phase after oral administration to rabbits, by increasing its urinary excretion. The fact that sodium bicarbonate exhibits different effects in the disposition of these two sulfonamides is an interesting example to gain a better understanding for the complexity of drug interaction.

Animals↗
PubMed1989

[Vincristine, adriamycin, mitomycin-C and UFT (VAM-UFT) therapy in progressive or recurrent breast cancer].

Since June 1984, 23 cases of progressive or recurrent breast cancers were treated with combination chemotherapy of VAM-UFT consisting of vincristine, adriamycin, mitomycin C and UFT. Clinical effects of VAM-UFT therapy were 3 CR, 12 PR, and the response rate was 65.2%. Its effective interval was 3 months. But the patients treated with over 4 cycles of VAM-UFT therapy showed an 85% response rate, with a 5-month effective interval. In each patient's background, a shorter disease free interval tended to be more highly effective, but other factors were not significant. Scirrhous carcinoma of pathology evidenced slightly high response rate. Compared with the survival time of patients treated with under 3 cycles and over 4 cycles of this therapy, the latter was significantly longer. Toxicity involved leukocytopenia (74%), thrombocytopenia (22%), anemia (30%), alopecia (91%), nausea and vomiting (87%) and stomatitis (35%), but cases in which the treatment was stopped were not observed. Therefore VAM-UFT therapy had a highly therapeutic effect, reflected in an 85% response rate, for progressive or recurrent breast cancers.

Adult↗
PubMed1989

[A case of glomus tumor of the stomach, including a review of the literature of 52 reported cases in Japan].

Discussed is a 62-year-old male who was admitted to hospital for an examination of the stomach. Physical examination and associated laboratory data uncovered no unusual results. On barium ingestion, however, an X-ray revealed an oval shaped filling defect at the greater curvature of the antrum. Further, endoscopic examination revealed half of a globular tumor with a surface redness and bridging folds radiating from the tumor. Examination of a biopsied specimen led to the determination of a glomus tumor and the patient underwent an operation. On operation, a well circumscribed submucosal tumor, 1.5 x 1.5 x 1.5 cm in size, with lobulation was found in the antral submucosal region, this tumor extending to the subserosa. A histopathological study of this neoplasm revealed that it consisted of irregular, swollen, blood vessel lumens lined with flattened endothelial cells, with surrounding aggregates of glomus cells forming lobules. In addition to this case, 52 cases of glomus tumors reported in the Japanese literature are discussed.

Biopsy↗
PubMed1989

Multi-organ damage (MOD) induced by cancer cachexia and its pathogenesis.

The intraperitoneal implantation of the ascitic hepatoma cells, AH-130 to rats induced marked atrophy of the systemic organs within 2 weeks, resulting in the animal death. By the method of Feulgen hydrolysis curve analysis, the amount of single-stranded DNA and the degree of DNA instability were shown to be increased in these atrophic organs. In keeping pace with the progression of the cachectic multi-organ damage (MOD), the amount of lipidperoxide and the activity of superoxide dismutase (SOD) as measured by electron spin resonance (ESR) were increased in the ascites toward the end stage of chachexia. The increased lipidperoxide and SOD induction reflect the increased production of active oxygens, especially superoxide. The marked systemic organ damage induced in cancer cachexia seems to be due to DNA damage by active oxygens.

Animals↗
PubMed1989

Methicillin-resistant Staphylococcus aureus in nosocomial infections in the surgical ward and operating room.

In this study 214 strains of Staphylococcus aureus were isolated from clinical specimens on the surgical ward from 1983 to 1988 and in addition, 62 airborne strains were collected in the operating room. Highly methicillin-resistant strains of S.aureus (H-MRSA, MIC greater than 100 micrograms/ml) not detected in 1983 showed a significant increase in frequency by 1987 accounting for about 60% of MRSA (MIC greater than or equal to 12.5 micrograms/ml). Countermeasures instituted in 1987 such as the use of disinfectant chlorhexidine alcohol significantly decreased the frequency of MRSA and H-MRSA isolates in 1988. In our study of coagulase type, MRSA type IV strains were predominant until 1984, whereas after 1986 type II was prevalent. All airborne strains collected in the operating room were methicillin-sensitive S.aureus, with type VII currently epidemic. We therefore concluded that cross infection with MRSA took place on the surgical ward rather than in the operating room.

Cross Infection↗
PubMed1989

[Multiple myeloma].

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Bone Marrow Transplantation↗