Biomedical subjects

Kenji Otsubo

Publications and source records attributed to Kenji Otsubo.

23 records · Page 2Linked to original sources

PubMed2003

The antiplatelet aggregation effects of aspirin suppositories.

To confirm that aspirin suppositories are an effective treatment for acute ischemic stroke, we examined the suppressive effects of 200-mg aspirin suppositories on platelet aggregation. Aspirin suppositories suppressed platelet aggregation induced by ADP or collagen, and the suppression continued for 24 h. There was no significant difference in suppression of platelet aggregation between aspirin administered by suppository and orally given aspirin. These results suggest that aspirin suppositories are a useful treatment for acute ischemic stroke.

Adenosine Diphosphate↗

PubMed2003

[Simultaneous determination of carbaryl and propanil in human serum and urine by on-line column-switching technique followed by automatic reversed-phase HPLC].

Carbaryl and propanil in human serum and urine were determined by automatic on-line column enrichment technique followed by reversed-phase HPLC with photometric detection. Human serum was filtered through a membrane filter (0.45 micron pore size) and an aliquot of 0.1 ml of the filtrate was diluted with water up to 1 ml. The solution of 0.8 ml was directly injected to automatic HPLC without any preparation. Urine was incubated with beta-glucuronidase/arylsulfate for 16 hours at 37 degrees C. The resultant solution was then filtered through a membrane filter and the filtrate was analyzed by the similar manner as serum. Carbaryl and propanil in the sample solution were concentrated on a pre-conditioned ODS mini-column. After washing the mini-column with 5% methanol, they were separated by an ODS analytical column (Cosmosil 5 C18-MS, 250 x 4.6 mm i.d.) with acetonitrile/water (30:70, v/v) eluent and detected with a UV detector. Carbaryl and propanil in serum were detected at 220 and 210 nm, respectively. On the other hand, in order to separate from blank peaks, carbaryl and propanil in urine were detected at 290 and 260 nm, respectively. The presented HPLC method requires neither manual procedure of solid-phase nor liquid-liquid extraction. Calibration curves for carbaryl and propanil were linear over the range of 5 ng/ml-2 micrograms/ml in both serum and urine. Real serum (ng/ml level) and urine (microgram/ml level) samples were analyzed by the presented HPLC method. Effect of seventeen pesticides on the determination of carbaryl and propanil were investigated. All pesticides did not interfere with the determination except for thiuram.

Carbaryl↗

PubMed2002

Neurotoxicity induced by tacrolimus after liver transplantation: relation to genetic polymorphisms of the ABCB1 (MDR1) gene.

BACKGROUND: Tacrolimus is a substrate of P-glycoprotein (PGP) encoded by the multidrug resistant (MDR)1 gene (ABCB1). PGP, a multidrug efflux pump, restricts the distribution of tacrolimus in the brain. In this study, we investigate the correlation of ABCB1 gene polymorphism with tacrolimus-induced neurotoxicity in patients after liver transplantation. METHODS: The genotype of 6 patients with neurotoxic events and 11 patients without neurotoxic events was analyzed by polymerase chain reaction (PCR), and 8 mutations were detected. In addition to laboratory findings and patient characteristics, the contribution of mutations in the ABCB1 gene was evaluated with stepwise discriminant function analysis. RESULTS: High tacrolimus concentration, liver dysfunction, and mutation at position 2677 in exon 21 were demonstrated as positive predictors of tacrolimus-induced neurotoxicity. CONCLUSION: It is indicated that blood concentrations, liver function, graft weight, and polymorphism in the ABCB1 gene are important factors in tacrolimus-induced neurotoxicity.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2002

Role of human MDR1 gene polymorphism in bioavailability and interaction of digoxin, a substrate of P-glycoprotein.

OBJECTIVE: Our objective was to quantitate the contribution of the genetic polymorphism of the human MDR1 gene to the bioavailability and interaction profiles of digoxin, a substrate of P-glycoprotein. METHODS: The pharmacokinetics of digoxin was studied in 15 healthy volunteers, who were divided into 3 groups (n = 5 each) on the basis of genotyping for the MDR1 gene, in a 4-dose study after single doses of digoxin alone (0.5 mg orally and intravenously) and coadministered with clarithromycin (400 mg orally for 8 days). The dose of digoxin was reduced during the clarithromycin phase (0.25 mg orally and intravenously). RESULTS: The bioavailability of digoxin in G/G2677C/C3435, G/T2677C/T3435, and T/T2677T/T3435 subjects were 67.6% +/- 4.3%, 80.9% +/- 8.9%, and 87.1% +/- 8.4%, respectively, and the difference between G/G2677C/C3435 and T/T2677T/T3435 subjects was statistically significant (P <.05). The MDR1 variants were also associated with differences in disposition kinetics of digoxin, with the renal clearance being almost 32% lower in T/T2677T/T3435 subjects (1.9 +/- 0.1 mL/min per kilogram) than G/G2677C/C3435 subjects (2.8 +/- 0.3 mL/min per kilogram), and G/T2677C/T3435 subjects having an intermediate value (2.1 +/- 0.6 mL/min per kilogram). Coadministration of clarithromycin did not consistently affect digoxin clearance or renal clearance. However, a significant increase in digoxin bioavailability was observed in G/G2677C/C3435 subjects (67.6% +/- 4.3% versus 85.4% +/- 6.1%; P <.05) but not in the other 2 genotype groups. CONCLUSION: The allelic variants in the human MDR1 gene are likely to be associated with altered absorption and/or disposition profiles of digoxin and P-glycoprotein-mediated drug interaction

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2002

Polymorphism of MDR1 gene in healthy japanese subjects: a novel SNP with an amino acid substitution (Glu108Lys).

We discovered a novel single nucleotide polymorphism (SNP) at position 325 (G325A) in exon 5 of the multidrug-resistance 1 (MDR1) gene in a study of 37 healthy Japanese subjects. Details are as follows. SNP, 020614Honda001; GENE NAME, human P-glycoprotein (MDR1); ACCESSION NUMBER, M29427; LENGTH, 25 bases; 5'-ATGAATCTGGAGG/AAAGACATGACCA-3'. This SNP is expected to cause an amino acid substitution (Glu108Lys). In this study, one homozygote and one heterozygote for G325A were identified.

Journal Article↗