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Biomedical subjects

T Tateishi

Publications and source records attributed to T Tateishi.

At least 73 records · Page 4Linked to original sources

Corrosion resistance, mechanical properties, corrosion fatigue strength and cytocompatibility of new Ti alloys without Al and V.

The effects of various metallic ions using various metallic powders on the relative growth ratio of fibroblasts L929 and osteoblasts MC3T3-E1 cells were carried out. Ti, Zr, Sn, Nb and Ta had evidently no effect on the relative growth ratios of cells. Otherwise, Al and V ions exhibit cytotoxicity from a concentration of > or = 0.2 ppm. This Al effect on cells tend to be stronger in medium containing small quantity of V ions (< or = 0.03 ppm). The new Ti-15%Zr-4%Nb-4%Ta-0.2%Pd alloy exhibited a higher corrosion resistance in physiological saline solution. The addition of 0.02%O and 0.05%N to Ti-Zr alloy improved the mechanical properties at room temperature and corrosion fatigue strength. The relative growth ratios for the new Ti alloy plate and the alloy block extraction were unity. Further, the relative growth ratios were almost unity for the new Ti alloy against apatite ceramic pins up to 10(5) wear cycles in Eagle's MEM solution. However, there was a sharp decrease for Ti-6%Al-4%V ELI alloy from 3 x 10(4) wear cycles as V ion was released during wear into the wear test solution since the pH of the Eagle's MEM increases with increasing wear cycles.

3T3 Cells↗

In vitro diagnosis of axillary lymph node metastases in breast cancer by spectrum analysis of radio frequency echo signals.

Axillary lymph node status is of particular importance for staging and managing breast cancer. Currently, axillary lymph node dissection is performed routinely in cases of invasive breast cancer because of the lack of accurate noninvasive methods for diagnosing lymph node metastasis. We investigated the diagnostic ability of ultrasonic tissue characterization based on spectrum analysis of backscattered echo signals to detect axillary lymph node metastasis in breast cancer in vitro compared with in vitro B-mode imaging. Immediately after surgery, individual lymph nodes were isolated from axillary tissue. Each lymph node was scanned in a water bath using a 10-MHz instrument, and radio frequency data and B-mode images were acquired. Spectral parameter values were calculated, and discriminant analysis was performed to classify metastatic and nonmetastatic lymph nodes. Forty histologically characterized axillary lymph nodes were enrolled in this study, including 25 nonmetastatic and 15 metastatic lymph nodes. A significant difference existed in the spectral parameter values (slope and intercept) for metastatic and nonmetastatic lymph nodes. Spectral parameter-based discriminant function classification of metastatic vs. nonmetastatic lymph nodes provided a sensitivity of 93.3%, specificity of 92.0%, and overall accuracy of 92.5%. In comparison, B-mode ultrasound images of in vitro lymph nodes provided a sensitivity of 73.3%, specificity of 84.0%, and overall accuracy of 80.0%. Receiver operating characteristic (ROC) analysis comparing the efficacy of both methods gave an ROC curve area of 0.9888 for spectral methods, which was greater than the area of 0.8980 for B-mode ultrasound. Hence, this in vitro study suggests that the diagnostic ability of spectrum analysis may prove to be markedly superior to that of B-mode ultrasound in detecting axillary lymph node metastasis in breast cancer. Because of these encouraging results, we intend to conduct an investigation of the ability of spectral methods to classify metastatic axillary lymph nodes in vivo.

Adult↗

A comparison of the inhibitory effects of four volatile anaesthetics on the metabolism of chlorzoxazone, a substrate for CYP2E1, in rabbits.

BACKGROUND: Halothane inhibits in vitro and in vivo activity of cytochrome P-450 (CYP) 2E1. There are several fluorinated volatile anaesthetics besides halothane, and most of them are defluorinated by CYP2E1. It is unclear whether other fluorinated anaesthetics inhibit the in vivo activity of CYP2E1. METHODS: We compared the inhibitory effects of therapeutic concentrations of four inhalational anaesthetics, halothane, enflurane, isoflurane, and sevoflurane, on chlorzoxazone metabolism in rabbits receiving artificial ventilation. RESULTS: All four inhalational anaesthetics decreased arterial blood pressure and increased plasma chlorzoxazone concentration. However, no significant differences in the plasma chlorzoxazone concentration were found between the four anaesthetics. The estimated chlorzoxazone clearance increased after beginning inhalation with all four agents, but no significant difference in clearance was noted between agents. CONCLUSIONS: At therapeutic concentrations, the in vivo inhibitory effect on chlorzoxazone metabolism was similar for all four inhalational anaesthetics examined, even though their chemical characteristics and extent of hepatic metabolism differ considerably.

Anesthetics, Inhalation↗

Liver damage induced by bile duct ligation affects CYP isoenzymes differently in rats.

We examined the influence of liver damage induced by bile duct ligation on the activity and the expression of hepatic cytochrome P450 (CYP) 1A, 2B, 2C6, 2C11, 2E1 and 3A2 in male Sprague-Dawley rats. In the ligation group, testosterone 2 alpha-, 16 alpha-, and 6 beta-hydroxylase activities were severely decreased, whereas ethoxyresorufin O-deethylase and progesterone 21-hydroxylase activities relatively remained. Pentoxyresorufin O-deethylase and chlorzoxazone 6-hydroxylase activities were reduced to approximately one thirds those of control. The protein contents of these isoenzymes expressed in hepatic microsomes of the ligation group were decreased to 45%, 32%, 79%, 13%, 58%, and 23% of control for CYP1A, 2B, 2C6, 2C11, 2E1 and 3A2, respectively. The rank order of magnitude of the influence of bile duct ligation on CYP isoenzymes, assessed by the reduction in the enzyme activity and the protein content, corresponded with each other except CYP1A. The reduction of the enzyme activities significantly correlated with the reduction in the protein contents of different isoenzymes. These results suggested that bile duct ligation affected CYP isoenzyme activities and contents with different extent.

Animals↗

Mechanical properties of hydroxyapatite and OH-carbonated hydroxyapatite single crystals.

Single-crystal hydroxyapatite and OH-carbonated hydroxyapatite have bending strength much higher than that of dense hydroxyapatite ceramic, indicating potential applicability to a load-bearing biomaterial. However, the effects of carbonate on the strength are less clear. The objective of the present study was to determine the bending strength and Young's modulus of these single crystals with carbonate contents from 0 to 0.62 in CO2 wt%. Three-point bending tests were performed by means of a modified ultra-microhardness tester with a span of 380 microm and a bending direction <210> of the single crystals. The crystals were broken in air, water, and air after immersion in a cell culture medium for 3 wks. The average Young's modulus of the single crystals was from 54 to 79 GPa. The average bending strength of the single crystals in air was 500+/-184, 468+/-205, 513+/-151, and 450+/-162 MPa for those with 0, 0.09, 0.37, and 0.62 wt% carbonate, respectively. No significant decrease in strength was found for hydroxyapatite single crystals both in water and after the immersion in the medium. However, the strength of OH-carbonated hydroxyapatite single crystals decreased significantly by 23 to 43% in water in proportion to the carbonate content. The strength of single crystals with 0.37 and 0.62 wt% carbonate decreased significantly, even after the immersion in the medium. Therefore, hydroxyapatite single crystals are superior to OH-carbonated hydroxyapatite single crystals as a biomaterial for a load-bearing purpose.

Air↗

Effects of sodium nitroprusside on the catecholamine synthetic pathway in the adrenal medulla of rats.

We studied the effect of sodium nitroprusside (SNP), a nitric oxide (NO) donor, on tyrosine hydroxylase (TH) activity and epinephrine and norepinephrine levels in the adrenal medulla of rats. TH activity and the levels of epinephrine and norepinephrine in the adrenal medulla of the SNP+nicotine (Nic)-treated group were increased significantly compared to those in the control, Nic-treated and SNP-treated groups. Furthermore, methylene blue inhibited this increase in TH activity. The data suggest that the NO derived from SNP may increase TH through the guanylyl cyclase pathway in the presence of Nic.

Adrenal Medulla↗

Pharmacokinetics of KW-4679 in the elderly: single-dose and multiple-dose trials.

We evaluated the pharmacokinetics of KW-4679, a new antiallergic agent, in the elderly in trials of both single and multiple dosing. In the single-dose trial, the pharmacokinetics of a single dose of 10 mg KW-4679 in elderly male subjects was compared with those in young male subjects. In the multiple-dose trial lasting 6 consecutive days with elderly male subjects, the pharmacokinetics of the last dose of 10 mg KW-4679 were compared with those of the first dose to evaluate the accumulation of KW-4679 and/or its metabolites. In the single-dose trial, the maximum concentration and the area under the concentration time curve of KW-4679 in the elderly subjects were significantly greater than those in the young subjects, while the apparent total body clearance was significantly lower in the elderly subjects. There was no significant difference in the fraction of KW-4679 excreted in the urine between the elderly and the young subjects. The renal clearance of KW-4679 in the elderly subjects was significantly lower than that in the young subjects. Although the renal clearance was correlated with the creatinine clearance, the renal clearance was significantly greater than the creatinine clearance, suggesting that this agent undergoes renal tubular secretion. In the multiple-dose trial, all pharmacokinetic parameters examined, except the maximum concentration, showed no difference between the first and the last administration. No accumulation of KW-4679 or its metabolites could be detected in the elderly subjects examined in the 6-day multiple-dose trial, though the present results suggest the dose should be reduced in the elderly subjects who have lower creatinine clearance.

Adult↗

Effect of hypoalbuminemia on the disposition of theophylline. Comparative study with Sprague-Dawley rats and a mutant Sprague-Dawley hyperlipidemic strain with hypoalbuminemia.

We demonstrated the effect of hypoalbuminemia on theophylline disposition in rats. The pharmacokinetic parameters in Sprague-Dawley rats (SDRs) were compared with those in spontaneously hyperlipidemic rats (HLRs), which had approximately one half the serum albumin concentration of the SDRs, after a single 10 mg/kg injection (iv) of theophylline. Theophylline clearance (CL) in the HLRs was increased 1.6-fold, and the AUC was decreased by 36%. Although the elimination t1/2 was not significantly different between the two types of rats, the distribution volume (Vd) was increased significantly in the HLRs, compared with the SDRs. The free theophylline concentration in the SDRs was one half of the total concentration. In contrast, the free theophylline concentration in the HLRs was approximately equal to the total concentration. The enzymatic activities and apoprotein expression levels of CYP1A were decreased significantly in the HLRs, compared with the SDRs. The total theophylline CL was increased in HLRs with hypoalbuminemia, even though they exhibited lower enzymatic activity and CYP1A expression than did the SDRs. Because the unbound fraction and Vd of theophylline in HLRs were much larger than those in SDRs, we conclude that hypoalbuminemia may contribute to an increase in the Vd and a decrease in the CL for theophylline.

Animals↗

Osteopontin involvement in integrin-mediated cell signaling and regulation of expression of alkaline phosphatase during early differentiation of UMR cells.

To clarify the function of osteopontin in osteoblast differentiation, we have examined the signal transduction pathway in an osteoblastic cell line (UMR106-6) bound to osteopontin, fibronectin, vitronectin and collagen type I surfaces. This was done by investigating the production and autophosphorylation of focal adhesion kinase (FAK) and the expression of alkaline phosphatase (ALP) at the transcription level. Results suggest that osteopontin was not only responsible for the autophosphorylation of FAK but regulated the expression of ALP, which was strongly correlated with FAK activity. These results suggest that osteopontin might act as a trigger in the early differentiation of osteoblasts.

Alkaline Phosphatase↗

Solubility product of OH-carbonated hydroxyapatite.

Information on the solubility of OH-carbonated hydroxyapatite, Ca10(PO4)6(CO3)x(OH)2-2x, previously has not been available. In the present study the solubility product (Ksp) of OH-carbonated hydroxyapatite was measured in a 0.1 M acetic acid and sodium acetate buffer solution in a pH range of 4.0-5.8 at a CO2 partial pressure of 10(-3.52) atm. The equilibrium solubility increased with the increase of carbonate content. The Ksp values decreased with the decrease of pH. For example, Ksps were 10(-119), 10(-123), and 10(-130) for pure hydroxyapatite at pH 4.9, 4.5, and 4.1, respectively. The decrease of Ksp was not accounted for by calcium-carbonate complexation. Ksp measured at isoelectric points (L) was expressed as pL = 118.65 - 0.47316 x (CO2 wt%)2.4176. From this formula, the L values were calculated for pure and fully carbonated hydroxyapatite as 10(-118.7) and 10(102.8), respectively. The L value for pure hydroxyapatite agreed with values measured under carbonate-free conditions. Therefore, the L values were regarded as the Ksp for OH-carbonated hydroxyapatite excluding errors arising from carbonate contamination in the solution.

Air Pressure↗

Colchicine biotransformation by human liver microsomes. Identification of CYP3A4 as the major isoform responsible for colchicine demethylation.

Colchicine disposition involves both active biliary and renal excretion of parent drug, and at least in mammals a substantial fraction undergoes hepatic demethylation prior to excretion. We investigated the biotransformation of [3H]colchicine in a panel of microsomal preparations obtained from sixteen human liver samples. The production rate of the main metabolites of colchicine's 3-demethylcolchicine (3DMC) and 2-demethylcolchicine (2DMC), was linear in relation to incubation time, cytochrome (P450) content, and substrate concentration. Following the incubation of colchicine (5 nM) with microsomes in the presence of an NADPH-generating system for 60 min, 9.8% and 5.5% of the substrate were metabolized to 3DMC and 2DMC, respectively. The formation rate of colchicine metabolites exhibited a marked variation between the different microsomal preparations. The formation rates of both colchicine metabolites were correlated significantly with nifedipine oxidase activity, a marker of CYP3A4 activity (r = 0.96, P < 0.001), but not with the metabolic markers of CYP2A6, CYP2C19, CYP2C9, CYP2D6, and CYP2E1 activities. Chemical inhibition of CYP3A4 by preincubation with gestodene (40 microM) or troleandomycin (40 microM) reduced the formation of 3DMC and 2DMC by 70 and 80%, respectively, whereas quinidine, diethyldithiocarbamate, and sulfaphenazole had no inhibitory effect. Similarly, antibodies raised against CYP3A4 almost completely abolished colchicine demethylation and nifedipine oxidase activity, but preimmune IgG had no effect. In conclusion, colchicine was metabolized to 3DMC and 2DMC by human liver microsomes. The production of colchicine metabolites was mediated by CYP3A4, and its rate varied greatly between microsomal preparations obtained from different liver samples. The coadministration of colchicine with known inhibitors or substrates of CYP3A4 may inhibit colchicine metabolism, resulting in concentration-related toxicity.

Colchicine↗

Fretting corrosion resistance and fretting corrosion product cytocompatibility of ferritic stainless steel.

To avoid nickel ion release from SUS317L as an implant material, a new type of nickel, commercially free, of high purity, and high chromium ferritic stainless steel, was developed. The new stainless steel (FJ) was studied for aspects of fretting corrosion and cytocompatibility compared with SUS317L. A pin-on-plate fretting corrosion test in an artificial physiologic solution, and cell culture in media with the addition of the artificial physiologic solution used for fretting was conducted. Resistance to the fretting induced crevice corrosion of FJ was higher than that of SUS317L because of the favorable electrochemical stability of the FJ alloy. The amount of iron ion or colloidal fine particles released from FJ was about a quarter of that from SUS317L, although the weight loss of a pin of FJ was almost 5/3 that of SUS317L. The artificial physiologic solution used for SUS317L fretting was more harmful to the growth of L929 and MC3T3-E1 cells than that used for FJ fretting. FJ was therefore superior to SUS317L as a biomaterial, judging from the resistance to fretting-induced crevice corrosion, electrochemical stability, and the cytocompatibility of fretting corrosion products.

3T3 Cells↗

Bending strength of synthetic OH-carbonated hydroxyapatite single crystals.

Although hydroxyapatite (HAP) is applied to medical implants because of its biocompatibility, no data on mechanical strength of HAP single crystals were yet available, partly due to the difficulty in obtaining sufficiently large single crystals. In the present study the bending strength of OH-carbonated hydroxyapatite (CHAP) single crystals containing carbonate of 0.09 CO2 wt % prepared hydrothermally was determined in three-point bending tests. The three-point bending tests were performed using a modified ultra micro-hardness tester with a span of 380 micrograms and a bending direction of <210>. The CHAP single crystals were broken in air, water, and air after immersion in alpha minimum essential medium (alpha MEM) + 10% fetal bovine serum (FBS) for 3 weeks. The average bending strength of the CHAP single crystals was 468 +/- 205, 361 +/- 199 and 501 +/- 212 MPa in air, water, and air after immersion in alpha MEM + 10% FBS, respectively. In all cases the maximum strength at each crystal thickness value decreased in inverse proportion to the thickness.

Animals↗

Sex- or age-related differences were not detected in the activity of dihydropyrimidine dehydrogenase from rat liver.

We examined the influence of ageing and gender on the activity of dihydropyrimidine dehydrogenase (DPD) in male and female Sprague-Dawley rats at 3, 8, 40 and older than 60 weeks of age. The body and liver weights of male rats at 8 weeks and older of age were heavier than those of female rats at the same age and the ratio of liver to body weight was significantly reduced with ageing. The amount of produced 5FU metabolites, dihydrofluorouracil and fluoroureidopropionic acid, remained unchanged in the reaction mixture with the cytosol from any group of the rats. The formation rates of 5FU metabolite were 1.03+/-0.08/1.12+/-0.06, 0.98+/-0.11/1.16+/-0.10, 1.13+/-0.09/1.13+/-0.11 and 1.17+/-0.16/1.24+/-0.08 nmol min(-1) mg protein(-1) (mean+/-SD, male/female) in rats at 3, 8, 40 and older than 60 weeks of age, respectively. The results suggest that the DPD activity in the rat liver may not be affected by ageing or gender.

Aging↗

Effects of the estrous cycle and the gender differences on hepatic drug-metabolising enzyme activities.

The aim of the present study was to investigate the effects of the estrous cycle and physiological dose of estradiol (E2) and the gender difference on several hepatic drug-metabolising enzyme activities. Eight-week old female Sprague-Dawley rats at different stages of the estrous cycle [proestrous (P), estrous (E), and diestrous (D)] and 8-week old male rats were used in this study (n = 5, respectively). Serum E2 level at D was higher than that at E and lower than that at P. The hepatic cytochrome P450 content, aniline hydroxylase, ethoxycoumarin O-deethylase and aminopyrine N-demethylase activities in male were significantly higher than those in female at any stage of the estrous cycle and these activities in female remained unchanged during the estrous cycle. Neither the estrous cycle nor the gender difference affected the cytochrome b5 content. NADPH-cytochrome c reductase (fPT) activity at P was similar to that in male, and was significantly higher than that in E and D. fPT activity was increased by the administration of physiological dose of E2 in ovariectomized rats. Uridine diphosphate glucuronyltransferase (UDP-GT) activity at E was significantly lower than that at P or D and that activity in female was significantly lower than that in male. These results indicate that the estrous cycle, especially serum E2 level, may affect both fPT and UDP-GT activities.

Animals↗

Localized osteoarticular change due to joint immobilization; biomechanical test and bone densitometry in rat's hind limb model.

Bone change induced by knee immobilization was assessed on dissected femurs and tibias to clarify the influences upon the mechanical properties and their demands. Fifty-eight Wistar-Imamichi male rats (11-12 weeks old, body weight 350-450 g) were subjected to knee joint immobilization (150 degrees flexed position) on one side while the opposite side served as a control. Animals were killed in seven groups at time intervals of 1, 2, 3, 4, 5, 7, and 10 weeks. The hind leg was extirpated and prepared for (1) biomechanical analysis by the indentation method at the articular surfaces of the femoral condyle and head and at the subchondral bone of the proximal tibia, and for (2) dual-energy X-ray absorptiometry of the distal metaphysis of the femur. The biomechanical parameters measured induced dynamic stiffness and phase lag derived from forced oscillation (preload 3 N, cyclic load 2 N and 11 Hz, 35 Hz), and bone mineral density was analyzed. These were compared between the immobilized side and control side, and among the seven time groups. The biomechanical results showed an early change of osteocartilaginous properties at the femoral condyle, a late response at the tibial subchondral bone, and no change at the femoral head. The measurement of bone mineral density revealed that a very sensitive reaction started within 1-2 weeks. This study provides objective data demonstrating that disuse or lack of mechanical stress greatly affects the remodeling activity for homeostasis of joints, and dramatically impairs normal bone mineral density next to the immobilized joint in young animals.

Absorptiometry, Photon↗