Search PubMed⌕ Search

Biomedical subjects

T Kumai

Publications and source records attributed to T Kumai.

At least 55 records · Page 3Linked to original sources
PubMed1998

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↗
PubMed1998

Histopathological study of nonosseous tarsal coalition.

Histopathological analysis was performed on 55 feet in 48 patients with nonosseous tarsal coalitions. Histological findings were similar to those observed at the tendinous attachment site of Osgood-Schlatter disease, accessory navicular, and bipartite patellae. No nerve elements were observed in the fibrocartilaginous tissue at the coalition. Nerve elements were present only in periosteum and articular capsule surrounding the coalition. Pain in the tarsal coalition is not mediated by nerve elements at the coalition site itself. It is assumed that the pain is caused by mechanical abnormality that results from incomplete coalition. Incomplete coalition produces microfractures and remodelings on the boundaries between bone and the coalition, which then lead to degenerative changes. This mechanical abnormality seems to induce pain via free nerve endings in the periosteum and in the articular capsule surrounding the coalition.

Adolescent↗
PubMed1998

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↗
PubMed1998

Tarsal tunnel syndrome caused by coalition associated with a ganglion.

We examined seven patients with tarsal tunnel syndrome in one foot caused by talocalcaneal coalition and a ganglion. We excised the coalition and the ganglion in six of them. All the patients had pain, sensory disturbance in the sole, and a positive Tinel's sign. Older patients with a long history showed atrophy and weakness of the plantar muscles. Talocalcaneal coalition can be diagnosed on a plain lateral radiograph and an anteroposterior radiograph externally rotated 20 degrees, and confirmed by CT. MRI is also useful for diagnosis. The coalitions were medial, and the ganglion had developed from the incomplete part of the coalition; it was multilocular in some patients. After resection, there was early pain relief but sensory disturbances and Tinel's sign persisted. The postoperative results were excellent in one patient, good in four and fair in one.

Adolescent↗
PubMed1998

Long-term results of Watson-Jones tenodesis of the ankle. Clinical and radiographic findings after ten to eighteen years of follow-up.

Thirty-seven chronically unstable ankles in thirty-six patients were operated on with use of a Watson-Jones tenodesis. Thirty-four ankles (thirty-three patients) were followed for a mean duration of thirteen years and eight months (range, ten to eighteen years) after the operation. There were nine male and twenty-four female patients. The mean age of the patients was thirty-one years (range, fourteen to fifty-seven years) at the time of the operation and forty-four years (range, twenty-eight to seventy years) at the time of the latest follow-up. At the time of the most recent follow-up evaluation, twenty-seven patients (twenty-eight ankles) were examined directly by one of us and twenty-five patients (twenty-six ankles) also were evaluated radiographically. The other six patients were interviewed, with use of a questionnaire, by telephone. Of the thirty-four ankles, nineteen had an excellent result (grade 1), eleven had a good result (grade 2), three had a fair result (grade 3), and one had a poor result (grade 4) according to the rating system of Good et al. The mean score (and standard deviation) on the ankle-hindfoot scale of the American Orthopaedic Foot and Ankle Society for the twenty-eight ankles that were examined directly by one of us was 90 +/- 9.3 points (range, 68 to 100 points). Progression of an exostosis at the edge of the joint was detected in eighteen (69 percent) of the twenty-six ankles that were examined radiographically, but narrowing of the joint space was not seen in any ankle. No relationship was detected between the clinical results and radiographic osteoarthrotic changes or the duration of follow-up. The results did not deteriorate over the long term.

Adolescent↗
PubMed1998

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

A comparison of hepatic cytochrome P450 protein expression between infancy and postinfancy.

We immunochemically measured the contents of 9 different cytochrome P450 (CYP) isoenzymes expressed in the liver and compared them between two groups: one group of 6 infant and 4 perinatal patients and one group of 10 patients after infancy (over 1 year old). CYP protein expressed in human liver can be divided into three groups on the basis of expression pattern: (a) CYP2A6, 2C9, 2D6, 2E1, and 3A were present in all samples and no difference was observed between the two groups; (b) CYP1A2, 2B6, and 2C8 were expressed more after infancy than during infancy; and (c) CYP3A7, which has been considered a major CYP enzyme in fetal liver microsomes, was expressed in all infants as well as the four perinatal patients, whereas it was detected in only 2 patients after infancy. These results implied that CYP2A6, 2C9, 2D6, 2E1, and 3A are already expressed during perinatal and infant period, while CYP1A2, 2B6, and 2C8 are expressed highly in subjects over 1 year old, and CYP3A7 disappeared after infancy.

Adolescent↗
PubMed1997

The effects of streptozotocin-induced hypoinsulinemia on serum lipid levels in spontaneously hyperlipidemic rats.

We compared the effects of streptozotocin (STZ) treatment on serum cholesterol and lipoprotein levels in spontaneously hyperlipidemic rats (HLR), a hereditary hyperlipidemic model animal, with those in Sprague-Dawley rats (SDR). The body weight of control SDR and HLR were increased continuously for 30 days. Both SDR and HLR lost their body weight after STZ administration. Glucose levels of SDR and HLR were significantly increased by STZ treatment. Insulin levels were markedly decreased in HLR compared with those in SDR. Serum cholesterol and triglyceride levels of HLR treated with STZ were significantly higher than those of untreated HLR. The increment of both levels in HLR was much larger than that in SDR. The high density lipoprotein (HDL) cholesterol level of the STZ-treated HLR was significantly lower than that of untreated HLR. In the STZ-treated HLR the intensities of both bands of the very low density lipoprotein (VLDL) and the low density lipoprotein (LDL) were higher than those in untreated HLR, while the intensity of any lipoprotein band remained unchanged between STZ-treated and control SDR. The atherogenic index (the ratio of total cholesterol level minus HDL cholesterol level of HDL cholesterol level) in the STZ-treated HLR was significantly high compared with that in other groups. The STZ-treated HLR showed the extremely hyperlipidemic state and this animal might be useful in experiments for the development of atherosclerosis or the drug evaluation for the agents used in hyperlipidemia.

Animals↗
PubMed1997

Halothane inhalation inhibits the metabolism of chlorzoxazone, a substrate for CYP2E1, in rabbits.

We demonstrated the inhibitory effect of halothane (HAL) inhalation on the metabolism of chlorzoxazone (CZZ), a substrate for CYP2E1, in a bolus and a continuous injection study in rabbits receiving artificial ventilation. In a bolus injection study, the inhalation of 1.0% HAL significantly increased the half-life and the area under the curve and decreased the clearance of CZZ compared with those variables in midazolam administration. In a continuous injection study, the effect of various concentrations of inhaled HAL on plasma CZZ concentration at steady state was compared. Systolic and diastolic arterial blood pressure were decreased dose-dependently after 0.5%, 1.0%, or 2.0% HAL was inhaled. Although the plasma concentration of CZZ was increased 2.5-fold after 3 h of HAL inhalation, there was no significant difference in mean plasma concentrations among the groups treated with 0.5%, 1.0%, or 2.0% HAL. In contrast, the plasma concentration of lidocaine, a substrate for CYP3A, remained unchanged after 1.0% HAL was inhaled. These results suggest that general anesthesia obtained with HAL inhalation will affect the metabolism of drugs administered concomitantly when the drug is a substrate for CYP2E1.

Anesthesia, Inhalation↗
PubMed1997

Effects of ovariectomy and estrogen replacement on aorta angiotensin-converting enzyme activity in rats.

We investigated the possibility that physiological doses of estrogen protect against atherosclerotic change produced by changes in vascular angiotensin-converting enzyme (ACE) activity. Rats were ovariectomized, and after 14 days, treated with estradiol-17 beta (0.2 microgram/rat) for 14 weeks. Aorta ACE activity significantly increased in the ovariectomized rats, and decreased following estradiol-17 beta administration to a level not different from proestrous control rats. These results suggest that the lack of estrogenic action increases atherosclerotic change associated with changes in aorta ACE activity and that estrogen replacement therapy reduces the risk of atherosclerotic change associated with the decrease of aorta ACE activity.

Administration, Oral↗
PubMed1997

Enhancement of the affinity of androgen receptor in the adrenal medulla of spontaneously hypertensive rats.

We investigated the alteration of tyrosine hydroxylase (TH) mRNA expression and androgen receptor in the adrenal medulla of spontaneously hypertensive rats (SHR). The TH mRNA expression in the adrenal medulla of SHR was higher than that of Wistar Kyoto rats (WKY). The testosterone increased the TH mRNA expression of SHR, but not WKY. The affinity of androgen receptor in the adrenal medulla of SHR was higher than that of WKY; however, the number of androgen receptor was not different. These results suggested that the increased binding affinity of the androgen receptor of SHR may be related to TH gene transcription in the adrenal medulla.

Adrenal Medulla↗
PubMed1996

The activity of dihydropyrimidine dehydrogenase from rat liver was not affected by any of five 5-hydroxytryptamine antagonists.

We estimate the influence of five 5-hydroxytryptamine receptor (5-HT3) antagonists on the activity of dihydropyrimidine dehydrogenase (DPDase), the rate-limiting enzyme in 5-fluorouracil (5FU) metabolism. The activity of DPDase from the rat liver was compared in the cytosol mixture of 5FU incubated with or without each of five 5-HT3 antagonists. DPDase activity was not altered in the presence of any 5-HT3 antagonist studied here. It may be inferred from these results that the any 5-HT3 receptor antagonist examined in this study has little or no effect on fluorouracil catabolism.

Animals↗
PubMed1996

Preliminary examination of the influence of incubation time or cytosolic protein concentration on dihydropyrimidine dehydrogenase activity.

We examined the influence of incubation time or cytosolic protein concentration on the metabolite production of 5-fluorouracil (5FU). Although the activity of dihydropyrimidine dehydrogenase (DPDase) from rat liver is considered to be retained for up to 60 min, the production rate of 5FU metabolites was reduced, probably due to depletion of the substrate in 40 mumol/l and lower concentration of 5FU. Since the ratio of the metabolite production rate to the cytosolic protein became smaller in higher concentrations of cytosolic protein, the DPDase activity should be compared in the same concentration of cytosolic protein. The production rate of 5FU metabolites was considered to be linear up to 40 mumol/l 5FU incubated with 500 micrograms cytosolic protein. The rate of the metabolite production calculated by one-point sampling significantly correlated with the enzyme activity by the multi-point sampling method. Minimizing sampling points to determine the DPDase activity would save time and expense.

Animals↗
PubMed1996

Elevated tyrosine hydroxylase mRNA levels in medulla oblongata of spontaneously hypertensive rats.

The present study has investigated the expression of tyrosine hydroxylase (TH) mRNA and its activity in medulla oblongata of spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). The TH mRNA levels were determined by Northern blot and dot blot analyses. The TH activity and the expression of TH mRNA in medulla oblongata of SHR were significantly higher than those of WKY. These results suggest that the hypertension of SHR may be related to the high activity of TH due to the high level of TH mRNA which increases norepinephrine levels in the medulla oblongata.

Animals↗
PubMed1996

Isolated first naviculocuneiform joint coalition.

Clinical analysis was performed on 60 feet in 40 patients with isolated first naviculocuneiform coalitions. The most common symptom was a mild pain at the medioplantar site of the first naviculocuneiform joint. Fifteen feet (25%) were asymptomatic. Some cases had been treated erroneously as osteoarthritis or bony cyst before diagnosis. We divided coalitions morphologically into three patterns based on computed tomography findings: irregular, cystic, and combined pattern. Based on the mean age of each pattern, we hypothesized that initial irregular coalitions gradually develop into cystic and, finally, combined patterns. Considering the modest number of reported cases, this condition might easily be overlooked in many patients or may be related to ethnic characteristics. We suggest that the actual incidence of first naviculocunei-form coalitions should be investigated again.

Adolescent↗