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Biomedical subjects

T Tateishi

Publications and source records attributed to T Tateishi.

At least 109 records · Page 6Linked to original sources

In vitro biocompatibility, mechanical properties, and corrosion resistance of Ti-Zr-Nb-Ta-Pd and Ti-Sn-Nb-Ta-Pd alloys.

There is much discussion about the toxic effect of vanadium and aluminum contained in Ti-6Al-4V alloy for prosthetic implants. The goal of the present investigation was to develop new titanium alloys with sufficient mechanical properties using more biocompatible alloying elements: zirconium, tin, niobium, tantalum, and palladium. The relative growth rates of L929 and MC3T3-E1 cells were significantly higher when cultured with the extraction of Ti-10Zr-8Nb-2Ta-0.2Pd or Ti-15Zr-4Nb-2Ta-0.2Pd alloys than when cultured with the extraction of Ti-6Al-4AV ELI alloy. The tensile strength, elongation, and reduction of area for Ti-15Sn-4Nb-2Ta-0.2Pd alloy were 989 MPa, 14.4%, and 49.3%, respectively, surpassing Ti-6Al-4V ELI alloy. (ASTM F138-84); those for Ti-15Zr-4Nb-2Ta-0.2Pd alloy were 725 MPa, 23.6% and 54.9%, respectively. More than 15% addition of tin as well as zirconium deteriorated the tensile properties. Titanium release into a 5% hydrochloric acid solution from the new titanium alloys was 20-50 micrograms/cm2 per day, though that from Ti-6Al-4V ELI alloy was 1300 micrograms/cm2 per day. The optimum alloy compositions are Ti-15Zr-4Nb-2Ta-0.2Pd and Ti-15Sn-4Nb-2Ta-0.2Pd, judging from cytocompatibility, corrosion resistance, and mechanical properties. The former is characterized by its higher level cytocompatibility and corrosion resistance, while the latter is characterized by mechanical properties.

Alloys↗

Interethnic difference in omeprazole's inhibition of diazepam metabolism.

OBJECTIVES: To compare the effect of omeprazole, a substrate and inhibitor of CYP2C19, on diazepam metabolism in white and Chinese subjects. SUBJECTS AND METHODS: The study, which took place at a clinical research center in a University Hospital, was designed as a double blind, crossover, two-stage study; each stage lasted 21 days and was separated by 4 weeks. Subjects were eight white and seven Chinese men who were extensive metabolizers of debrisoquin and mephenytoin. The subjects received, in a randomized order, omeprazole, 40 mg/day, and placebo for 21 days, followed by a 10 mg oral dose of diazepam. Diazepam and desmethyldiazepam plasma concentrations were determined by HPLC during a 26-day period after diazepam administration. RESULTS: In white subjects omeprazole treatment decreased diazepam clearance by 38% +/- 4.4% and increased desmethyldiazepam area under the plasma concentration-time curve (AUC) by 42.4% +/- 7.0%. In contrast, diazepam oral clearance decreased by only 20.7% +/- 7.3% and desmethyldiazepam AUC decreased by 25.4% +/- 4.6% in the Chinese group. The decrease in diazepam clearance and the prolongation in diazepam and desmethyldiazepam elimination half-lives after administration of omeprazole were significantly greater in the white group than in the Chinese group (p < 0.03, p < 0.001, and p < 0.004, respectively). In the absence of omeprazole, diazepam oral clearance was marginally greater (mean +/- SEM) (34.4 +/- 2.8 ml/min versus 25.2 +/- 3.5 ml/min, p = 0.057, respectively) and the AUC of desmethyldiazepam was significantly lower (8794 +/- 538 micrograms/L.hr versus 16,358 +/- 2985 mg/L.hr, p = 0.04, respectively) in the white subjects compared with the Chinese subjects. CONCLUSION: The extent of the inhibitory effect of omeprazole on diazepam metabolism is dependent on ethnicity. Further studies are needed to determine the mechanism responsible for this phenomenon.

Adult↗

Subcutaneous pheomycotic cyst of the finger caused by Exophiala jeanselmei: association with a wooden splinter.

A 58-year-old man with mild glucose intolerance noted a subcutaneous cystic nodule on the ventral aspect of his ring finger. He had experienced trauma to the finger while gardening five weeks before the lesion occurred. Exophiala jeanselmei was isolated and identified on culturing of aspirate from the cystic nodule. The nodule was then removed surgically, and a wooden splinter was found close to the subcutaneous fibrous cyst, suggesting that the causal organism had entered the subcutaneous tissue with the wooden splinter.

Cysts↗

Influence of aging on the oxidative and conjugative metabolism of propranolol.

The influence of aging on the hepatic metabolism of propranolol, i.e. conjugation, side-chain oxidation and ring oxidation, was investigated in 32 in-patients aged 30 to 84 yrs. Plasma propranolol concentration and main urinary metabolites [propranolol glucuronide (PPLG), naphthoxylactic acid (NLA), and 4-hydroxypropranolol (40HP)] were determined after a single oral dose of 20 mg propranolol. There were significant correlations between age and 1) maximum propranolol concentration, 2) area under the plasma concentration-time curve, and 3) elimination half-life. The apparent oral clearance of propranolol was inversely correlated with age. Partial metabolic clearance (PMC) to 40HP (ring oxidation) and PMC to NLA (side-chain oxidation) were significantly correlated with age, while PMC to PPLG was not. These observations suggest that there are age-related reductions in two oxidizing capacities, while there is no significant influence of aging on the conjugating capacity. The age-related reduction in oral clearance of propranolol may be mainly caused by the decline in the capacity of two different oxidation pathways.

Adrenergic beta-Antagonists↗

Renal clearance of lomefloxacin is decreased by furosemide.

The interaction between lomefloxacin, a new quinolone, and furosemide, a loop diuretic, has been examined. Oral lomefloxacin 200 mg and furosemide 40 mg were given together or separately to 8 healthy subjects, and blood and urine samples were obtained over the following 12 h. The plasma concentrations of lomefloxacin following coadministration with furosemide were higher than after lomefloxacin alone and its AUC was increased, and its total and renal clearances were decreased. No change in the pharmacokinetics of furosemide was found after coadministration of lomefloxacin. As quinolones and furosemide are reported to be excreted in urine by the renal tubular anion transport system, the present results suggest that the renal tubular secretion of lomefloxacin is diminished by furosemide. It is not clear whether this pharmacokinetic interaction might be clinically important.

Adult↗

Different effects of antidepressants on dissociation of 3H-imipramine from solubilized binding sites of rat brain.

1. The effects of several antidepressants and 5-hydroxytryptamine on dissociation of 3H-imipramine from solubilized binding sites were investigated. 2. Binding sites were solubilized from rat brain membranes and gelfiltrated on a column of Sephacryl S-300. 3. Most of the agents used allowed biphasic dissociation with 1mM of displacing agent and without using dilution-induced dissociation. This biphasic dissociation without nonspecific effects of membranes may be due to the existence of low-affinity binding sites. 4. Dissociation of up to 40 min followed first-order kinetics. The dissociation half-life of 3H-imipramine with the various displacing agents was calculated at from 15.0 to 25.0 min, and the differences among the agents were not so significant as the attenuation or the acceleration of the dissociation was indicated. The lower concentration of the displacing agents may obscure the modulation of the dissociation.

Animals↗

Effect of mutations of ionic amino acids of cytochrome P450 1A2 on catalytic activities toward 7-ethoxycoumarin and methanol.

Catalytic efficiencies, percentages of rates of product formation per NADPH oxidized, and rates of product formation per O2 consumed of ionic mutants of cytochrome P450 1A2 (P450 1A2) were studied. Efficiencies of Lys99Glu, Lys453Glu, and Arg455Glu mutants for the hydroxylation reaction toward 7-ethoxycoumarin in the reconstituted system were much lower than that of the wild type (less than 17%), which corresponds to lower turnover numbers for these mutants. In contrast, the catalytic efficiencies for the hydroxylation reaction toward methanol of the three mutants were more than 45% that of the wild type in spite of these mutants' lower turnover numbers. Turnover numbers and catalytic efficiencies of Arg137Leu and Lys401 Glu mutants toward both substrates were comparable to those of the wild type. The electron-transfer rate from the reductase to the heme of P450 1A2 was decreased by 30% upon addition of excess methanol, while it was not influenced by addition of excess 7-ethoxycoumarin. The turnover numbers toward both 7-ethoxycoumarin and methanol as well as the rate constant of electron transfer were decreased by 25-40% by raising the concentration of KCl from 0 to 300 mM in the reconstituted system containing 50 mM potassium phosphate buffer. The turnover numbers toward both substrates of the above-mentioned five ionic mutants caused by tert-butyl hydroperoxide in the absence of the reductase and NADPH were comparable to those of the wild type. The effect of phospholipid constituents on the catalytic activity toward 7-ethoxycoumarin of the wild type was also studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Effects of diltiazem and cimetidine on theophylline oxidative metabolism.

The effect of diltiazem or cimetidine pretreatment on the inhibition of theophylline oxidative metabolism was investigated in nine healthy male nonsmokers. Diltiazem 60 mg, cimetidine 400 mg, or placebo was given orally three times daily for 3 days in a randomized three-way crossover manner. Both diltiazem and cimetidine pretreatment decreased the mean theophylline clearance (0.702 on placebo versus 0.641 on diltiazem, P < .05, and 0.542 mL/minute/kg on cimetidine, P < .01), resulting in prolonged mean theophylline half-life (7.58 on placebo versus 8.59 on diltiazem, P < .05, and 10.08 hours on cimetidine, P < .01) with no change in volume of distribution. The mean metabolic clearances for three major theophylline metabolites, 1-methyluric acid (1-MU), 1,3-dimethyluric acid (1,3-DMU), and 3-methylxanthine (3-MX), were reduced significantly by cimetidine (28%; P < .05, 32%; P < .01, and 33%; P < .01, respectively). Conversely, diltiazem significantly reduced only the mean metabolic clearance of 1,3-DMU by 21% (P < .05) without changes in that of 1-MU or 3-MX. These results suggest that cimetidine inhibited both N-demethylation and 8-hydroxylation of theophylline, whereas diltiazem exerted little influence on N-demethylation in spite of inhibition in 8-hydroxylation.

Adult↗

Pharmacokinetics of beta-methyldigoxin in subjects with normal and impaired renal function.

Beta-methyldigoxin (beta-MD) was administered orally (0.2 mg) to 24 patients with various degrees of renal function, to investigate its pharmacokinetic characteristics related to renal function. Serum and urine collected until 120 hours after dosing were assayed for beta-MD and digoxin by high-performance liquid chromatography and fluorescence polarization immunoassay method. The steady-state volume of distribution decreased proportionately as creatinine clearance (CLCR) decreased, although steady-state volume of distribution of hemodialysis patients had large interindividual variability, and their mean value was not different from that of patients with normal renal function. Both renal clearance of beta-MD and digoxin were significantly correlated with CLCR (r = .820, P < .001 and r = .822, P < .01, respectively), and the slope of regression line for beta-MD was only 44% that for digoxin. Significantly reduced urinary excretion of total drug (beta-MD plus digoxin) was shown in patients with CLCR below 50 mL/minute/1.48 m2. This study suggests that the dosage modification is not necessary until CLCR decreases to below 50 mL/minute/1.48 m2, but careful attention should be given in the use of beta-MD in patients with CLCR below this value.

Adult↗

The influence of pretreatment periods with diltiazem on nifedipine kinetics.

The effect of durations of diltiazem pretreatment on nifedipine kinetics was evaluated. Eighteen healthy male subjects were randomly allocated to three groups, 6 subjects each, for single doses of 60 mg diltiazem, and 3 days and 6 days with diltiazem 60 mg three times a day. All subjects received 20 mg nifedipine orally on two occasions using a double-blind cross-over, placebo-controlled method. No significant difference on pharmacokinetic parameters of nifedipine without diltiazem were observed among three groups. The single dose with 60 mg diltiazem significantly increased the area under the plasma concentration-time curve (AUC) for nifedipine compared with that in control an average of 35.1% (P < .05) and decreased the total body clearance (CL) an average of 24.0% (P < .05). Three days and 6 days pretreatment with diltiazem 60 mg three times a day significantly increased mean nifedipine AUC to 151.1% (P < .01), 188.0% (P < .05) of control values, and decreased CL to 58.2% (P < .01), 63.9% (P < .05) of control values, respectively. The elimination half-life (t1/2) of nifedipine were significantly prolonged both after 3 days' and after 6 days' pretreatment of diltiazem. These results suggest that diltiazem affects the nifedipine kinetics rapidly and pretreatment duration dependently. A clinically important drug interaction may occur when both drugs are administered simultaneously.

Administration, Oral↗

Influence of lisinopril on urinary electrolytes excretion after furosemide in healthy subjects.

It has been reported that the urinary excretions of chloride (Cl), potassium (K), and magnesium (Mg), but not sodium (Na), after furosemide, a loop diuretic, were decreased by pretreatment with lisinopril, an ACE inhibitor in hypertensive subjects. The electrolytes disturbance induced by furosemide might be ameliorated by lisinopril. The present study re-examines this potential drug interaction in healthy subjects. Lisinopril (20 mg) or its matching placebo was given orally using a double-blind, crossover design. Four hours after lisinopril administration, furosemide (20 mg) was injected intravenously and urine was collected during the following intervals: 0-0.5, 0.5-1, 1-1.5, 1.5-2, 2-3, 3-4, and 4-6 hours. Blood samples for plasma furosemide concentration were obtained at 0.5, 1, 1.5, 2, 3, 4, and 6 hours after the agent. There were no significant differences between the two trials in plasma concentrations of furosemide or urinary excretions of the agent. Urine volume and urinary excretions of electrolytes (Na, Cl, K, and Mg) after the furosemide with lisinopril administration were not significantly different from those of placebo at any observation period. These results suggest that the urinary excretions of electrolytes after furosemide administration are not influenced by pretreatment with lisinopril.

Adult↗

The effect of nifedipine on the pharmacokinetics and dynamics of diltiazem: the preliminary study in normal volunteers.

To evaluate the influence of nifedipine on the pharmacokinetics and the pharmacodynamics of diltiazem, five healthy subjects received 60 mg diltiazem orally on two occasions, diltiazem alone or after nifedipine pretreatment (10 mg three times daily for 3 days). After nifedipine pretreatment, the maximum concentration (Cmax) of diltiazem was increased and the time of Cmax was shortened, and the area under the concentration curve (AUC) tended to be increased. Although heart rate was increased, the corrected PQ interval tended to be prolonged after the nifedipine pretreatment. Both a decreased hepatic clearance and an increased bioavailability of diltiazem probably accounts for the increase in the Cmax and AUC of diltiazem after nifedipine pretreatment, and that might affect the pharmacodynamics of diltiazem.

Administration, Oral↗

Differences of chronopharmacokinetic profiles between propranolol and atenolol in hypertensive subjects.

Previous studies have shown that the absorption rate of a lipophilic, but not hydrophilic, agent is faster after the night dosage than after the morning dosage in nocturnal rodents. The present study examines whether such a difference in chronopharmacokinetic profiles between lipophilic and hydrophilic agents also exists in humans. Propranolol (20 mg), a lipophilic beta-blocker, or atenolol (50 mg), a hydrophilic beta-blocker, was given orally to 13 hypertensive patients at 9:00 AM (day trial) or 9:00 PM (night trial) by a crossover design. Plasma concentrations of propranolol and its metabolites, 4-hydroxypropranolol and naphthoxylactic acid, and atenolol were determined just before and at 0.5, 1, 1.5, 2, 3, 4, 6, 12, and 24 hours after treatment. Maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) of propranolol in the day trial were significantly greater than those in the night trial. Time to maximum plasma concentration (tmax) was significantly shorter in the day trial. No significant difference was observed in the elimination half-life between the two trials. There were similar administration time-dependent changes in the Cmax for 4-hydroxypropranolol and naphthoxylactic acid. On the other hand, although the Cmax of atenolol was greater and its tmax was shorter in the day trial, the differences did not reach significance. These results suggest that propranolol, but not atenolol is absorbed more rapidly after the morning dosage than after the night dosage. Based on these findings, the authors speculate that the absorption rate of a lipophilic, but not hydrophilic, agent is faster after the morning dosage than after the night dosage in humans.

Administration, Oral↗

The effect of age on diurnal variation in the pharmacokinetics of propranolol in hypertensive subjects.

There is diurnal variation in the absorption rate of propranolol in younger subjects. This study was undertaken to examine the effect of age on the chronopharmacokinetics of propranolol. We gave 20 mg of propranolol orally to 13 younger and 11 older hypertensive subjects at 09.00 h (day study) or 21.00 h (night study) in a cross-over design. Plasma concentrations of propranolol and its metabolites, 4-hydroxypropranolol and naphthoxylactic acid, were determined just before and at 0.5, 1, 1.5, 2, 3, 4, 6, 12, and 24 h after dosage. In the younger subjects the absorption rate constant (ka) of propranolol and its maximum plasma concentration (Cmax) were significantly higher and the time to maximum concentration (tmax) was significantly shorter in the day than at night. There were similar time-variant changes in Cmax and tmax for 4-hydroxypropranolol and naphthoxylactic acid. In contrast, there were no time-variant changes in ka, Cmax and tmax of propranolol and its metabolites in the older subjects. These results suggest that propranolol is absorbed more rapidly after morning dosing than after night-time dosing in younger but not in older subjects. Based on these findings, we speculate that the time-variance in the absorption rate or first-pass elimination, or both, of propranolol diminish with age.

Adult↗

In-vitro evaluation of the cytocompatibility of wear particles generated by UHMWPE/zirconia friction.

Cytotoxicity of wear products generated by UHMWPE/yttria partially stabilized zirconia (YPSZ) friction and UHMWPE/surface-nitrided Ti-6Al-4V friction in pseudo-extracellular fluid (PECF) at 37 degrees C was evaluated. Though the amount of abraded UHMWPE against YPSZ was almost the same as that against nitrided Ti-6Al-4V, the wear products generated by UHMWPE/YPZ friction significantly inhibited cell growth while those by UHMWPE/nitrided Ti-6Al-4V friction showed no growth inhibition. Dissolved Zr and Y ions were at least 70 times less than the amount causing growth inhibition. The cytotoxicity was caused mainly by the particles less than 0.22 mum in size. Amorphous zirconium-containing particles (5-20 nm) found in the PECF, formed presumably by stress corrosion, would be a responsible factor for the cytotoxicity.

Biocompatible Materials↗

Research and development of alumina and zirconia artificial hip joint.

The object of the experiments was to discover the static and dynamic load-carrying capacity of a prosthetic system consisting of a titanium allow stem, zirconia ceramic ball head and UHMWPE (ultra-high molecular weight polyethylene) socket molded in the ceramic shell, the latter two were both of 22 mm in diameter. The components of the artificial hip joint were placed in a vertical position and load was applied, alternating between 0 and 10 kN and then 12 kN with a frequency of 30 Hz under Ringer's solution up to 10 7 cycles respectively. After 2 x 10 7 cycles there was no sign of damage to be observed among the system tested using the joint simulator. This seems to be a very high safety factor compared with loads occurring in vivo.

Evaluation Studies as Topic↗