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Biomedical subjects

S Uno

Publications and source records attributed to S Uno.

At least 37 records · Page 2Linked to original sources
PubMed1999

Pharmacokinetic drug interactions between ampiroxicam and sulfaphenazole in rats.

The aim of the present study was to determine the effect of sulfaphenazole (SP) on the pharmacokinetics of ampiroxicam (AM) which is metabolized by cytochrome P-450 (CYP) 2C9, since SP is a potent inhibitor of CYP 2C9, and so a dramatic pharmacokinetic drug interaction between both drugs is assumed after dosing. Single intravenous and oral administrations of AM (5 and 7.5 mg/kg piroxicam equivalent, respectively) and SP (80 and 120 mg/kg, respectively) to rats did not significantly alter the elimination kinetics of AM and piroxicam (PX) converted from AM. When SP was preloaded orally at 2 h before the dosing of AM, and when AM and SP were orally coadministered for 7 d, the elimination of PX from plasma was slightly retarded and the area under the plasma concentration-time curve (AUC) was increased 77 and 53%, respectively, but not significantly, compared with those after AM alone. On the other hand, a significantly decreased metabolic conversion of PX to 5'-hydroxyPX in plasma was observed by these treatments (p<0.05). In order to clarify the mechanism for the interaction, hepatic and intestinal metabolizing enzyme activities, CYP, uridine 5'-diphosphoglucuronyltransferase (UDPGT) and aryl esterase, were assayed after single and multiple oral administrations of AM or AM and SP. The enzyme activities were hardly inhibited by the treatment, indicating that the inhibition of CYP and hydrolytic enzymes by SP was approximately denied. These results suggest that SP does not significantly affect the pharmacokinetics of AM and PX in rats. However, the pharmacokinetic drug interaction between both drugs in man may not always be ignored.

Administration, Oral↗
PubMed1999

The influence of configuration factors on cavity adaptation in compomer restorations.

The effect of configuration factor (C-factor) on cavity adaptation was investigated in three compomer and one resin composite restorations. Eighty-four cylindrical dentin cavities (C-factor: approximately 2.5, 3.0 or 4.0) prepared on flat coronal dentin surfaces were filled with the materials in combination with their proprietary adhesive systems. Cavity adaptation was microscopically examined after 15 minutes storage in water at the top surface and at other four sites along the cavity walls. Additionally, indentation testing was performed for each material at 20 minutes and 24 hours after irradiation. Regression analysis revealed no relationship between C-factor and gap dimension in compomer restorations at any of the measuring sites, while a logarithmic relation was found only at the cavity floor of the composite fillings. All materials showed maturation of mechanical properties. The elastic component of the indentation was smaller in compomers than in the composite. It was concluded that C-factor had no influence on the cavity adaptation for compomer restorations. This might be due to reduced stress generation at the bonding interface caused by relatively low mechanical properties immediately after curing, less elasticity, and water absorption in compomers.

Compomers↗
PubMed1999

[Acute vincristine neurotoxicity in a non-Hodgkin's lymphoma patient with Charcot-Marie-Tooth disease].

A 44-year-old, previously healthy man with a diagnosis of non-Hodgkin's lymphoma (NHL, diffuse large B-cell type, stage IIA) was treated with combination chemotherapy including vincristine (VCR). After receiving a cumulative dose of VCR, he experienced rapid and marked weakening which progressed to quadriplegia and bulbar palsy. Prior to this therapy, the patient had no neurological problems, and his siblings were asymptomatic. Physical examination identified pes cavus (hollow foot), and electrodiagnostic studies showed markedly slower nerve conduction velocity of myelinated fibers, with abundant "onion bulb" formations. Chromosomal analysis detected 17p11.2-12 duplication, thus yielding a diagnosis of Charcot-Marie-Tooth (CMT) 1A. CMT disease is a familial neuromuscular disorder, and the incidence is approximately 1 in 2,500. We concluded that if CMT disease is diagnosed, vincristine should be avoided due to the potential severity of neurotoxicity to small doses.

Adult↗
PubMed1999

Pharmacokinetic study of S-1, a novel oral fluorouracil antitumor drug.

S-1 is a novel oral fluorouracil antitumor drug that combines three pharmacological agents: tegafur (FT), which is a prodrug of 5-fluorouracil (5-FU); 5-chloro-2,4-dihydroxypyridine (CDHP), which inhibits dihydropyrimidine dehydrogenase (DPD) activity; and potassium oxonate (Oxo), which reduces gastrointestinal toxicity. Phase I and early Phase II clinical trials have already been completed. On the basis of the results of these trials, 80 mg/m2/day, given daily in two divided doses after breakfast and supper, a 28-day consecutive oral regimen is recommended. In this study, we investigated the pharmacokinetics of 5-FU, intact FT, CDHP, and Oxo, after administration of S-1, at a standard dose of 80 mg/m2/day, in advanced cancer patients. Twelve patients were recruited to the study; 5 patients with gastric cancer, 4 with colorectal cancer, and 3 with breast cancer. Among them, analysis was conducted on 12 patients for single administration and on 10 patients for consecutive administration. The initial dose of S-1 for each patient was determined according to his/her body surface area (BSA) as follows: for BSA < 1.25 m2, 80 mg/body/day; for 1.25 m2 < or = BSA < 1.5 m2, 100 mg/day; and for 1.5 m2 < or = BSA, 120 mg/day. For single administration, half of the standard dose was used. For 28-day consecutive administration, the standard dose was given daily in two divided doses. The average single dose per BSA was 35.9 mg/m2 (31.7-39.7 mg/m2). Pharmacokinetic parameters of plasma 5-FU were as follows: Cmax, 128.5 +/- 41.5 ng/ml; Tmax, 3.5 +/- 1.7 h; AUC(0-14), 723.9 +/- 272.7 ng x h/ml; and T(1/2), 1.9 +/- 0.4 h. In the 28-day consecutive regimen, there were no fluctuations in pharmacokinetics nor any drug accumulation. Because the pharmacokinetics of orally administered S-1 is almost similar to that of continuous i.v. infusion of 5-FU, we concluded that S-1 may improve patients' quality of life.

Adult↗
PubMed1999

[Multi-drug resistant breast cancer responding to chemotherapy with docetaxel (taxotere: TXT)].

The patient was a fifty-five year old female who had stage IVb advanced breast cancer with hypoxia due to bilateral pulmonary metastases and lymphangitis. The cancer was adriamycin (ADM) and multi-drug resistant. We administered docetaxel (taxotere: TXT) 60 mg/m2 every 3 weeks. After 2 courses, the pulmonary metastases had become remarkably reduced in size and hypoxia was reduced and performance status (PS) improved. Major toxic defects were grade-4 neutropenia and hair loss. The patient could be discharged from the hospital without O2 inhalation and enjoyed a better quality of life (QOL). This chemotherapy is thought to be effective against ADM and multi-drug resistant breast cancer.

Antineoplastic Agents, Phytogenic↗
PubMed1998

Inhibition of the expression of the gene for the angiotensin AT1 receptor by angiotensin II in the rat adrenal gland.

The expression of angiotensin AT1A and AT1B receptor mRNA after continuous angiotensin II administration was investigated in the rat adrenal gland. Angiotensin AT1 receptor mRNA detected by Northern blot analysis decreased to 52.7+/-16.1% of control after the administration of angiotensin II (20 microg/h) for 24 h, and to 70.8+/-8.0% after 1 week. A low dose of angiotensin II (0.2 microg/h) also decreased angiotensin AT1 receptor mRNA to 73.0+/-5.5% after 1 week. Competitive reverse transcription and polymerase chain reaction (RT-PCR) experiments revealed that both angiotensin AT1A and AT1B receptor mRNAs decreased after administration of angiotensin II (20 or 0.2 microg/h) for 1 week. Analysis of the angiotensin AT1A promoter by using luciferase-reporter system showed that angiotensin II (up to 1 microM) did not have any effects on the promoter activity (106+/-5.7% after 0.1 microM angiotensin II stimulation) in Y1 cells and cultured vascular smooth muscle cells, although phorbol myristate acetate (PMA) decreased the promoter activity by about 40% compared with control. These results suggest that angiotensin AT1 receptor gene expression in the rat adrenal gland is inhibited by angiotensin II and it may not be due to suppression of promoter activity. Other mechanisms such as destabilization of angiotensin AT1 receptor mRNA or angiotensin II-induced increased blood pressure may be involved in the inhibition.

Adrenal Glands↗
PubMed1998

Chromosomal DNA patterns and gene stability of Pichia pastoris.

We have clearly resolved four chromosomal bands from four Pichia pastoris (Komagataella pastoris) strains by using contour-clamped homogeneous electric field gel electrophoresis. The size of the P. pastoris chromosomal bands ranged from 1.7 Mb to 3.5 Mb and total genome size was estimated to be 9.5 Mb to 9.8 Mb; however, chromosome-length polymorphisms existed among four strains. Thirteen cloned genes isolated from strain GTS115 were assigned to the separated chromosomes, revealing that different hybridization patterns were observed in the AOX2 and URA3 genes among strains. P. pastoris is frequently used as an efficient host for heterologous gene expressions. We analysed chromosomal stability of strain GTS115-derived recombinant cell expressing human serum albumin during serial cultivation under the condition of vegetative and non-selective growth. No chromosomal rearrangements were observed and the expression constructs integrated into the his4 locus on chromosome I were very stable even at 83 generations, suggesting that stable expression would be carried out even in large-scale fermentation.

Chromosomes, Fungal↗
PubMed1998

Regulation of tissue-type plasminogen activator (tPA) and type-1 plasminogen activator inhibitor (PAI-1) gene expression in rat hepatocytes in primary culture.

We have performed a comparative study on tPA and PAI-1 mRNA expression in primary cultures of rat hepatocytes and elucidated the possible regulation of these factors by certain hormonal stimulation. The tPA mRNA increased 2- to 4-fold in the presence of cholera toxin (CT), dibutyryl cyclic AMP (dbcAMP), or 3-isobutyl-1-methyl xanthine (IBMX), but slightly decreased in the presence of dexamethasone. The tPA activity was also changed by these agents in a similar fashion. On the contrary, PAI-1 mRNA decreased with CT, dbcAMP, or IBMX, but increased transiently with dexamethasone. From results obtained with cycloheximide, ongoing protein synthesis was judged to be required for both PAI-1 induction with dexamethasone and PAI-1 suppression with IBMX, but not for the tPA induction with IBMX. Dexamethasone exerted opposite regulatory effects on the tPA mRNA expression depending on its concentration: at 10(-8) to 10(-6) M, it suppressed the expression; whereas at 10(-10) M, it elevated the expression.

1-Methyl-3-isobutylxanthine↗
PubMed1998

Case report: Alanine aminotransferase deficiency detected in a patient with chronic hepatitis C.

We report a case of alanine aminotransferase (ALT) deficiency in a 68-year-old Japanese female with chronic hepatitis C. The serum was positive for antibody to hepatitis C virus (HCV) and HCV-RNA. Liver biopsy showed histological evidence of chronic active hepatitis. The level of serum aspartate aminotransferase (sAST) was elevated, but sALT was extremely low. The patient was followed up for her serum aminotransferase levels for 1.5 years under the treatment with ursodeoxycholic acid. The low sALT level persisted during all the follow-up period. The ALT activity in liver tissue was also decreased. Based on these findings, ALT deficiency was suspected. sALT activity was also found to be low in her two sons. This latter finding suggests the hereditary character of this abnormality.

Adult↗
PubMed1998

[Combination chemotherapy with cis-platinum and ifosfamide for hormone unresponsive prostate cancer].

PURPOSE: There is no effective therapy against hormone refractory prostate cancer. This led us to evaluate the effectiveness and toxicity of cis-platinum (CDDP) and ifosfamide (IFM) combination chemotherapy in the patients with hormone-unresponsive carcinoma of the prostate. METHODS: Patients with hormone-unresponsive prostate cancer were scheduled to receive CDDP 70 mg/m2 intravenously on day 1 and IFM 1.2 g/m2/day intravenously on day 1 through day 5 of 28-day cycle. RESULTS: Twenty seven patients with hormone unresponsive prostate cancer were enrolled onto this trial. Of these patients, seven (26%) demonstrated a partial objective response (PR), and ten (37%) a stable disease (ST). The response duration of PR cases lasted from 6 to 49 months with a median of 16 months and the response duration of PR + ST cases lasted from 3 to 36 months with a median of 10 months. Subjective improvement was obtained in 11 patients (41%). Survival duration of all cases were 4 to 89 months with a median of 23 months and probabilities of survival at 3 years and 5 years were 36% and 24%, respectively. The toxicity of this treatment was mostly mild to moderate, anemia (96%), leukocytopenia (89%), anorexia (81%), alopecia (67%), thrombocytopenia (44%), hematuria (38%), renal dysfunction (19%) and liver dysfunction (7%) were noticed. Severe toxicity was observed in two cases, one acute renal failure and one endotoxin shock. CONCLUSION: We conclude that CDDP and IFM combination chemotherapy was active regimen for hormone unresponsive prostate cancer.

Aged↗
PubMed1997

Induction of tissue-type plasminogen activator (tPA) and type-1 plasminogen activator inhibitor (PAI-1) as early growth responses in rat hepatocytes in primary culture.

Early growth response with respect to tissue-type plasminogen activator (tPA) and type-1 plasminogen activator inhibitor (PAI-1) gene expression was studied in rat hepatocytes in primary culture. The genes for tPA and PAI-1 could be categorized as a delayed early growth response (DER) gene and an immediate early growth response (IER) gene, respectively. The expression of tPA was much higher in growth-promoting than in static culture conditions (i.e., cultured at low density and/or on a collagen-coated dish), and that of PAI-1 was regulated in the opposite direction. Experiments using dibutyryl cAMP (dbcAMP) and H-89 showed that the cAMP/A-kinase system might be involved in the induction of the early growth response of tPA and in the augmentation of PAI-1 mRNA induction by dbcAMP. These fibrinolytic components, whose expression is closely associated with hepatocyte growth, may play important roles in pathophysiological events in the liver such as liver regeneration.

Animals↗
PubMed1997

Arterial ketone body ratio as a prognostic indicator in acute heart failure.

The arterial ketone body ratio (AKBR), an established clinical tool that reflects hepatic mitochondrial oxidation-reduction potential, predicts the outcome of patients with shock and multiple organ failure and the postoperative outcome in patients who have undergone major liver or heart surgery. The purpose of this study was to determine the prognostic significance of AKBR in patients with acute heart failure. The subjects of this study were 52 patients with acute heart failure. The following parameters were analyzed after Cox univariate hazard analysis was performed: AKBR, plasma norepinephrine, left ventricular ejection fraction, cardiac index, pulmonary arterial wedge pressure, sex, age, human atrial natriuretic peptide, endothelin-1, and cholesterol. The follow-up period was 30 weeks with cardiac death as the end point. Stepwise multivariate proportional hazard analysis revealed that AKBR was the most significant predictor of death, followed by norepinephrine and human atrial natriuretic peptide. Curve-fitting analysis revealed that the relationship between log (norepinephrine) and AKBR could best be described by two distinct lines, with their intersection at AKBR = 0.7 and norepinephrine = 418. With these results we conducted Kaplan-Meier analysis for AKBR > or = 0.7 and AKBR <0.7. The survival rate in patients with AKBR > or = 0.7 was 100%, whereas that in patients with AKBR <0.7 was 15% (p < 0.0001, log-rank analysis). These results indicate that AKBR is a novel independent predictor of death in heart failure.

Acute Disease↗
PubMed1997

Effect of cavity design on microleakage of resin-modified glass ionomer restorations.

PURPOSE: To investigate cavity sealing with resin-modified glass ionomer cements (RGIC) and a compomer relative to the design of Class V cavities crossing the CEJ. MATERIALS AND METHODS: Three types of cavities, 6 x 3 x 1.5 mm, were prepared buccally in human molars. Type 1: semicircular with 90 degrees cavo-surface angle; Type 2: as type 1, but with bevelled enamel margin; Type 3: V-shaped. The cavities were restored with the compomer Dyract (DYR), with one of the RGIC, Fuji II LC (FUJ), Photac-Fil (PHF) or Vitremer (VIT), or with the bonded resin composite system Gluma-CPS/Pekafill (GLP) as a reference. Six restorations in each group were finished immediately after curing and thermocycled 1500 between 5 degrees C and 55 degrees C. For Type 1 restorations, another set of six samples was stored in 23 degrees C water for 24 hours. After thermocycling and water storage, respectively, the specimens were immersed in 0.1% fuchsin. Two sections were made through the restoration to register microleakage on the four surfaces produced as depth of dye penetration coronally and apically by scores 0 (no) to 4 (beyond deepest part of cavity). The results were statistically analyzed by cavity type, site, and restorative material using Kruskal-Wallis ANOVA and Wilcoxon's two sample test at P = 0.05. RESULTS: When compared with water storage, thermocycling had no effect on dye penetration with FUJ and PHF, yet more pronounced microleakage at the enamel site was noted with DYR and VIT, and apically with DYR and GLP. Type 1 restorations leaked more than type 2 and 3 cavities for FUJ, VIT and GLP.

Analysis of Variance↗
PubMed1996

Ketone body ratios of the superior and inferior vena cava and of pulmonary arterial blood compared to that of arterial blood: central venous ketone body ratio as a substitute for the arterial ketone body ratio.

To investigate the ketone body ratio (acetoacetate/3-hydroxybutyrate) of central venous blood compared to that of peripheral arterial blood, the acetoacetate and 3-hydroxybutyrate concentrations in paired peripheral arterial and central venous or pulmonary arterial blood were measured. The ketone body concentrations in superior and inferior vena cava blood were significantly (P < 0.0001) lower than those in peripheral arterial blood, whereas those in pulmonary arterial blood were almost the same as those in peripheral arterial blood. These results indicate that ketone bodies were metabolized in the muscles, which reduced their levels in vena cava blood, but ketone bodies newly produced by the liver were transported to the right side of the heart via the hepatic vein, giving concentrations in pulmonary arterial blood that were almost the same as those in peripheral arterial blood. On the other hand, the correlation coefficients (r2) of the arterial blood ketone body ratio to the ratio of superior and inferior vena cava and pulmonary arterial blood were 0.897, 0.767 and 0.882, respectively. The ratios of central venous ketone body ratio/arterial blood ketone body ratio were 0.89 +/- 0.15 in the superior vena cava, 0.64 +/- 0.18 in the inferior vena cava and 1.01 +/- 0.15 in the pulmonary artery.

3-Hydroxybutyric Acid↗