Biomedical subjects

T Osanai

Publications and source records attributed to T Osanai.

At least 55 records · Page 3Linked to original sources

PubMed1996

A kinetic and dynamic study of oral alprazolam with and without erythromycin in humans: in vivo evidence for the involvement of CYP3A4 in alprazolam metabolism.

OBJECTIVE: To assess the possible involvement of CYP3A4 in the metabolism of alprazolam in vivo. METHOD: Twelve healthy male volunteers were randomly allocated to one of the two different treatment sequences, placebo-erythromycin or erythromycin-placebo, with an at least 6-week washout period between the two trial phases. Each volunteer received 400 mg erythromycin or matched placebo given orally three times a day for 10 days and an oral dose (0.8 mg) of alprazolam on the posttreatment day 8. Plasma concentration of alprazolam was measured up to 48 hours after the administration, and psychomotor function was assessed at each time of blood samplings with use of the Digit Symbol Substitution Test, visual analog scale, and Udvalg for kliniske undersøgelser side effect rating scale. RESULTS: Erythromycin significantly (p < 0.001) increased the area under the plasma concentration-time curves (200 +/- 43 versus 322 +/- 49 ng . hr/ml from 0 to 48 hours and 229 +/- 52 versus 566 +/- 161 ng . hr/ml from 0 hour to infinity), decreased the apparent oral clearance (1.02 +/- 0.31 versus 0.41 +/- 0.12 ml/min/kg), and prolonged the elimination half-life (16.0 +/- 4.5 versus 40.3 +/- 14.4 hours) of alprazolam. However, any psychomotor function variables did not differ significantly between the erythromycin and placebo trial phases. CONCLUSION: This study suggests that erythromycin, an inhibitor of CYP3A4, inhibits the metabolism of alprazolam, providing an in vivo evidence for the involvement of CYP3A4 in its metabolism. However, the kinetic change of alprazolam by erythromycin does not result in the pharmacodynamic change of this triazolobenzodiazepine, at least after single dosing.

Administration, Oral↗

PubMed1996

Distribution of Corynebacterium renale among apparently healthy rats.

We examined the distribution of Corynebacterium renale, a causative agent of urinary calculus, in clinically normal rats at 6 animal facilities in Japan. Swabs of the vulva and vaginal vestibule or prepuce of the rats were cultured for isolation of the organisms. C. renale has been isolated at only one animal facility, where cases of urinary calculus were reported several years ago. In this facility, 32% of female (43/135) and 22% of male (18/82) rats, 4-28 weeks old, were positive for C. renale. In contrast, 92 female and 169 male rats at other facilities without a history of the disease were negative for the organisms.

Animals↗

PubMed1996

Carbamazepine augmentation therapy in three patients with trazodone-resistant unipolar depression.

In three patients with trazodone-resistant unipolar depression, carbamazepine 400 mg/day was co-administered for 4 weeks. They all showed favourable responses; two non-delusional patients completely or almost recovered, while one delusional patient showed considerable improvement in depressive symptoms other than delusions of guilt. Plasma concentrations of trazodone and its active metabolite m-chlorophenylpiperazine (m-CPP) were decreased, while the m-CPP/trazodone ratio was increased in all cases. The present report suggests that carbamazepine augments antidepressant effects of trazodone by an enhancement of serotonin function.

Aged↗

PubMed1996

Effects of carbamazepine coadministration on plasma concentrations of trazodone and its active metabolite, m-chlorophenylpiperazine.

Effects of carbamazepine coadministration on plasma concentrations of trazodone and its active metabolite, m-chlorophenylpiperazine (m-CPP) were studied in six depressed patients treated with trazodone. The daily dose of trazodone was 150 mg in three cases and 300 mg in three cases. Carbamazepine, 400 mg/day, was coadministered for 4 weeks, and blood samples were taken before carbamazepine addition and at weekly intervals after the addition. Carbamazepine significantly (p < 0.01) decreased plasma concentrations of not only trazodone but also m-CPP at each week. On the average, plasma concentrations of trazodone and m-CPP at 4 weeks were 24 and 40% of the corresponding precarbamazepine values. This study thus suggests that carbamazepine coadministration decreases plasma concentrations of trazodone and m-CPP by inducing the metabolism of these compounds.

Anticonvulsants↗

PubMed1996

Chemical characterization of peroxidized low-density lipoprotein in plasma and aortic atheroma.

Hydroperoxidized cholesteryl linoleate (HPO-CL, spot X1) was produced by peroxidation of normal LDL isolated from plasma of healthy persons. Spot X stained on thin-layer chromatography plate (silica 60) between triglycerides and free fatty acids. The solvent mixture used consisted of petroleum ether 75, ethyl ether 25, and acetic acid 1. Spot X1 of plasma from healthy subjects stained slightly. It was also identified in plasma LDL of patients with atherosclerotic diseases, and in total lipids extracted from aortic atheroma obtained at autopsy. Whereas spot X1 obtained from plasma LDL of patients with atherosclerotic diseases consisted of HPO-CL, spot X1 obtained from aortic atheroma was reduced HPO-CL (hydroxide CL). Spot X1 of obtained from aortic atheroma was reduced HPO-CL (hydroxide CL). Spot X1 of aortic atheroma did not react to p-methoxydiphenylpyrenylphosphine (MP3)-an agent which shows only positive reaction to hydroperoxide chemical structures-although spot X1 of plasma LDL from atherosclerotic diseases reacted positively to MP3. Moreover, spot X1 obtained from aortic atheroma showed the same Rf value as that of the reduced HPO-CL. The IR profile of spot X1 obtained from aortic atheroma was similar to that of hydroxide CL, although the IR profiled HPO-CL was similar to that obtained from plasma LDL of atherosclerotic patients. In addition, HPO-CL was not recognized in the LDL fraction with clathrin-coated pits from aortic atheroma.

Adult↗

PubMed1996

Peroxidized low-density lipoprotein with four kinds of hydroperoxidized cholesteryl linoleate estimated in plasma of young heavy smokers.

AIM: To clarify the mechanisms of vascular complications due to heavy smoking, it was studied whether hydroperoxidized low-density lipoprotein (HPO-LDL) was estimated in plasma of young heavy smokers. METHOD: Plasmas were separated from 15 young male students (HS-M) who smoked more than 30 cigarettes/day over 5 years, and from 10 nonsmoker students (NS-M) too. LDL was isolated by ultracentrifugation. HPO-cholesteryl linoleate (HPO-CL) was identified by thin-layer chromatography (TLC), and lipid peroxide was measured by Determiner LPO (Kyowa Medics Co., Ltd, Tokyo, Japan). The molecular structure of lipid peroxide in LDL was identified using GMS analysis, HPLC chromatography and 1H-NMR analysis. RESULTS: (1) HPO-CL was clearly observed on the TLC in LDL lipids of HS-M but from NS-M it was barely found. (2) Lipid peroxide in LDL separated from HS-M consisted of HPO-CL and reduced HPO-CL. CONCLUSION: Peroxidized LDL was estimated in plasma with young heavy smokers. Because of injurious reactions in vessels of peroxidized LDL, it is considered that heavy smoking is one of the risk factors for vascular complications in heavy smokers.

Adult↗

PubMed1996

Sodium ionophore converts growth manner of vascular smooth muscle cells from spontaneously hypertensive rats.

OBJECTIVES: Vasoconstrictor peptides such as endothelin (ET) cause hypertrophy of vascular smooth muscle cells (VSMC) in Wistar Kyoto rats (WKY) and hyperplasia in spontaneously hypertensive rats (SHR). They also induce an increase in Na+ concentration ([Na+]i) and activate protein kinase C (PKC) independently. Therefore, we tested the hypothesis that the increase in [Na+]i may be involved in the conversion of growth manner under activated PKC in SHR VSMC. METHODS AND RESULTS: 10(-7) M phorbol ester (TPA) increased the diameter and protein content of VSMC from both strains under 18% serum conditions. Further addition of 10(-6) M gramicidin (Na+ ionophore) converted TPA-induced hypertrophy to hyperplasia, which was due to the quick transition from S to G2/M phase, only in SHR VSMC. Western blot analysis showed that serum- and TPA-induced tyrosine phosphorylation of mitogen-activated protein (MAP) kinase was potentiated by 10(-6) M gramicidin in SHR. [Na+]i, which was measured by sodium-binding benzofuran isophthalate (SBFI), was increased about 35 mM by 10(-6) M gramicidin in both strains, but TPA did not affect basal [Na+]i and the gramicidin-induced increase in [Na+]i. CONCLUSIONS: We conclude that sodium ionophore may convert hypertrophy to hyperplasia synergistically with activated PKC in SHR VSMC, possibly by MAP kinase phosphorylation.

Animals↗

PubMed1995

Protective effects of soy protein on the peroxidizability of lipoproteins in cerebrovascular diseases.

To study the mechanism of dyslipoproteinemia, lipoproteins [very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL)] were isolated from stroke patients and healthy persons by ultracentrifugation. Lipoproteins were dialyzed into copper dichloride solution to study the effects of soycreme administration on lipoprotein peroxidation. Blood was drawn from 15 patients with cerebral thrombosis who were not administered soycreme, 10 patients with cerebral thrombosis who were administered soycreme and 11 healthy persons. The lipoproteins were dialyzed into 5 mol/l copper dichloride solution for various lengths of time, and then lipid constituents in the lipoproteins were measured by thin-layer chromatography. After the dialysis, percentages of cholesteryl ester and triglyceride in various lipoproteins decreased significantly (P < 0.05 or 0.01) in both patient groups and in healthy persons. Spot X1 was found between triglyceride and free fatty acid on the thin-layer chromatography, and spot X2 was located between free fatty acid and free cholesterol after dialysis. Spots X1 and X2 reflect lipoprotein peroxidation. Percentages of these spots were higher in VLDL, LDL and HDL in the patient groups than in the healthy subjects. Soycreme administration suppressed the appearance of spots X1 and X2. Furthermore, blood cholesterol concentrations were reduced by the administration of soy protein. Thus, soy may be useful in the prevention and/or treatment of atherosclerosis.

Adult↗

PubMed1995

Trazodone treatment increases plasma prolactin concentrations in depressed patients.

m-Chlorophenylpiperazine (m-CPP), which is a metabolite of trazodone, is a serotonin agonist. To examine for the possibility that m-CPP is involved in biochemical effects during treatment with the parent compound, prolactin response to trazodone treatment (150 mg at bedtime for 3 weeks) was studied in 12 depressed patients. The means +/- S.D. of plasma prolactin concentrations before treatment, 12 h, and 1, 2 and 3 weeks after initiation of treatment were 9.1 +/- 5.6, 14.7 +/- 9.1, 15.3 +/- 8.5, 13.2 +/- 7.0 and 13.0 +/- 7.0 ng/ml, respectively. The mean prolactin concentrations at 12 h (p < 0.01), 1 week (p < 0.001) and 2 weeks (p < 0.05) were significantly higher than that before treatment. The present study thus shows that trazodone treatment increases prolactin concentrations, suggesting that m-CPP is involved in biochemical effects during treatment with the parent compound.

Adult↗

PubMed1995

Effects of various factors on steady state plasma concentrations of trazodone and its active metabolite m-chlorophenylpiperazine.

Effects of various factors on steady state plasma concentrations of trazodone and its active metabolite m-chlorophenylpiperazine (mCPP) were studied in 43 depressed patients (19 males, 24 females) receiving trazodone 150 mg at bedtime for 1-3 weeks. Sixteen cases were smokers, and 19 cases were also receiving various benzodiazepines. The means (and ranges) of plasma concentrations of trazodone and mCPP, and the mCPP/trazodone ratio were 619 (251-1059) ng/ml, 59 (32-139) ng/ml and 0.100 (0.044-0.219), respectively. Smokers had significantly (p < 0.05) lower plasma concentrations of trazodone and higher mCPP/trazodone ratios than non-smokers. Age, sex and co-administration of benzodiazepines did not affect any plasma concentrations or the mCPP/trazodone ratio. In 11 cases where the dose was increased to 300 mg, neither plasma concentration/dose ratios nor the mCPP/trazodone ratio changed significantly. The present study thus suggests that: (1) there is a large Interindividual variation in the metabolism of trazodone; (2) smoking enhances the metabolism, but age, sex and co-administration of benzodiazepines do not affect it; (3) trazodone and mCPP have linear kinetics.

Adult↗

PubMed1995

Inhibition of trazodone metabolism by thioridazine in humans.

To clarify the involvement of cytochrome P4502D6 (CYP2D6) in the metabolism of trazodone, the effects of coadministration of thioridazine, which is an inhibitor of this isozyme, on plasma concentrations of trazodone and its active metabolite m-chlorophenylpiperazine (m-CPP) were studied. The subjects were 11 depressed patients receiving trazodone at bedtime for 1-18 weeks. The dose was 150 mg in 10 patients and 300 mg in one. Thioridazine 40 mg/day was coadministered for 1 week, and blood samplings were performed before and after the coadministration. Thioridazine significantly (p < 0.001) increased plasma concentrations of both trazodone (713 +/- 252 vs. 969 +/- 370 ng/ml) and m-CPP (61 +/- 22 vs. 94 +/- 34 ng/ml). The present study thus suggests that CYP2D6 is involved in the metabolism of trazodone.

Adult↗

PubMed1995

High-performance liquid chromatographic determination of trazodone and 1-m-chlorophenylpiperazine with ultraviolet and electrochemical detector.

A high-performance liquid chromatographic (HPLC) assay was developed for the determination of trazodone and its metabolite, 1-m-chlorophenylpiperazine (m-CPP), in plasma. The high level of trazodone in plasma was detected by ultraviolet absorbance at 254 nm and the low level of m-CPP in plasma was detected by coulometric electrochemical detection at 840 mV on the series arrangement of two detectors. Pilsicainide as an internal standard for both compounds was monitored by both detectors. Trazodone and m-CPP in plasma were extracted by a rapid and simple procedure based on CN bonded-phase extraction, and C8 reversed-phase HPLC separation. Determination was possible for trazodone in the concentration range 100-2000 ng mL-1 and for m-CPP in the concentration range 5-100 ng mL-1. The recoveries of trazodone and m-CPP added to plasma were 81.0-84.2 and 68.0-73.2%, respectively, with coefficients of variation of less than 7.3 and 8.2%, respectively. The method is applicable to high level monitoring of trazodone and low level monitoring of m-CPP in plasma of healthy volunteers and patients treated with trazodone.

Chromatography, High Pressure Liquid↗

PubMed1995

Transformation of cultured human monocytes by peroxidized low-density lipoprotein.

To study the roles of peroxidized low-density lipoprotein (pox-LDL) during the formation of foam cells from human monocytes, monocytes isolated from normal human blood were incubated with RPMI alone, normal low-density lipoprotein (n-LDL) and copper pox-LDL. The concentrations of total cholesterol (TCH) and lipid peroxide in the human monocyte medium did not change significantly after incubation with RPMI medium alone or n-LDL, but those of TCH decreased slightly after incubation with pox-LDL for 24 h. Triglyceride (TG) concentrations in the culture medium of human monocytes decreased after incubation with all above substances. Ultrastructural studies showed that the monocytes changed to macrophages after incubation with RPMI alone or n-LDL and to foam cells after incubation with pox-LDL for 48 h. We conclude that TGs may be metabolized for ATP production by human monocytes. The energy may play a role in the transformation of monocytes to macrophages, and pox-LDL can induce transformation of monocyte-derived macrophages to foam cells.

Cell Differentiation↗

PubMed1995

Assignment of the bacterial agent of urinary calculus in young rats by the comparative sequence analysis of the 16S rRNA genes of corynebacteria.

Comparative 16S rRNA gene sequencing was used to assign four isolates of spontaneous urinary calculus in young laboratory rats. The phylogenetic relationships among the rat isolates and selected species of corynebacteria were also inferred. Based on the homology and evolutionary distance analysis, the 16S rRNA genes of the rat isolates were almost identical with that of Corynebacterium renale ATCC 19412. Also the results of the phylogenetic analysis showed a close relationship among the isolates and C. renale, but they were clearly different from C. pilosum, C. cystitidis, C. kutscheri and Rhodococcus equi. The results of the present study and previously published biochemical data demonstrate that the organism involving urinary infections in young rats is identified to be C. renale.

Animals↗

PubMed1995

[Expression of E-cadherin as related to prognostic factors and survivals in breast cancer].

E-cadherin (E-CD) expression and its clinicopathological implication were investigated in 26 patients with breast cancer by immunohistochemical staining. 12 out of 26 primary lesions (46%) express strong and homogeneous expression of E-cadherin (preserved type), while in 14 cases (54%), degree of E-CD expression was reduced, i.e., 8 patients with heterogeneous staining, 2 cases with weak but homogeneous, and 4 cases with lost expression of E-CD (reduced type). However, there was no statistically significant correlation among decrease of E-CD expression, histological features, and advanced stages of breast cancer. Analysis on survivals showed better prognosis in the group with preserved E-CD expression than without E-CD (follow up was more than 96 months or until death). These findings suggests that the patients with decreased E-CD expression may be associated with metastasis resulting in poor prognosis, and E-CD expression could be one of the prognostic factors.

Breast Neoplasms↗

PubMed1994

Spontaneous urinary calculus in young LEW rats caused by Corynebacterium renale.

Spontaneous urinary calculus was observed in only 27% of female LEW rats among nine inbred strains maintained in the Institute for Animal Experimentation. The condition occurred between 3 and 9 weeks of age with loss of weight, enlargement of the os urethral externum, anuria and general marasmus. All of the affected rats died from anuria 3 to 4 days after the onset. The affected rats had one to ten infected stones or many fine crystals of sand, which consisted of magnesium ammonium phosphate, in the urinary bladder and/or urethra. Analysis of microorganisms revealed that Corynebacterium renale, known as a causative agent of bovine pyelonephritis, was the most probable candidate for producing infection stones. This is the first report that the rat is spontaneously infected with C. renale. This could be a useful animal model for human urinary calculus and also for C. renale infection in the field of veterinary science.

Animals↗

PubMed1994

Plasma peroxidized low-density lipoprotein with hydroperoxidized cholesteryl linoleates estimated in patients with familial hypercholesterolemia.

A study was conducted to ascertain the presence of peroxidized low-density lipoprotein (LDL) in plasma and to determine the chemical structure of the peroxidized LDL so that the mechanism by which vascular complications develop may be elucidated in patients with familial hypercholesterolemia (FH). Family trees showing hypercholesterolemia and moderate grade thickness of the Achilles' tendon were confirmed in all patients. Cholesteryl ester, triglycerides (TG), free fatty acid (FFA), free cholesterol (FC), and phospholipids in normal LDL were stained on a thin-layer chromatography (TLC) plate, but from peroxidized LDL, spot X1 between TG and FFA, and spot X2 between FFA and FC were identified clearly except for the lipids recognized in normal LDL on the TLC plates. From intermediate-density lipoprotein (IDL), LDL1, and LDL2 of FH patients, spot X1 was clearly recognized. Hydroperoxidized cholesteryl linoleate (HPO-CL) was estimated and identified from Cu(2+)-treated standard CL, Cu(2+)-treated LDL and LDL obtained from FH patients by means of high-pressure liquid chromatography, mass spectrometry, nuclear magnetic resonance, positive reaction of p-methoxydiphenylpyrenyl-phosphine and various chemical reactions. The percentage of HPO-CL to total lipids in LDL was in the order of IDL < LDL1 < LDL2 in FH patients, and it was markedly higher in FH patients when compared to healthy persons. Spot X1 obtained from Cu(2+)-treated CL, from Cu(2+)-treated normal LDL and from LDL of FH patients was chemically identical, consisting of at least 4 kinds of HPO-CL isomer. LDL2-cholesterol levels were higher in FH patients than those of LDL1-cholesterol, whereas in healthy persons LDL1 cholesterol levels were higher compared to those of LDL2 cholesterol. The capacity of LDL2 for peroxidization by Cu2+ was greater than that of LDL1 in healthy persons. Biological functions, such as acceleration of platelet aggregation, great internalization into macrophages and injuries of the arterial endothelia, were reported for LDL with HPO-CL in our previous experiments. Thus, the existence of peroxidized LDL with HPO-CL may be one of the important risks for vascular complications in FH patients.

Adult↗

PubMed1994

Color Doppler imaging of orbital venous flow in dysthyroid optic neuropathy.

Color Doppler imaging was performed to evaluate the venous stasis in 39 orbits, including 9 optic neuropathy orbits, of 20 patients with dysthyroid ophthalmopathy and 22 orbits of 11 healthy subjects. The superior ophthalmic vein (SOV) was detected in 26 dysthyroid ophthalmopathy orbits and in 13 control orbits. The blood flow in the SOV was in the anteroposterior direction in 20 dysthyroid ophthalmopathy orbits and in 13 control orbits. Reversed flow, ie, the flow in the posteroanterior direction, was seen in 6 dysthyroid ophthalmopathy orbits and in none of the control orbits. In dysthyroid ophthalmopathy orbits, the blood flow in the SOV was reversed in 5 (36%) of the 14 orbits with apical orbital crowding observed on computed tomography, which means there was compression of the optic nerve by enlarged extraocular muscles, as compared to in 1 (4%) of the 25 orbits without apical orbital crowding (P < 0.05). The percentage of the orbits having reversed flow in SOV was 44% of dysthyroid ophthalmopathy orbits with optic neuropathy as opposed to 7% of those without optic neuropathy (P < 0.05). Reversed blood flow in the SOV strongly supported the existence of severe venous stasis in the orbits, which may be related to the development of dysthyroid optic neuropathy.

Adolescent↗