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Biomedical subjects

K Ohashi

Publications and source records attributed to K Ohashi.

At least 487 records · Page 27Linked to original sources

Chronopharmacological study of nitrendipine in healthy subjects.

Nitrendipine 20 mg or placebo was given orally to eight healthy subjects in a cross-over design separated by 1 or 2 weeks. Drug was given at 9:00 AM (morning dosage) or at 9:00 PM (evening dosage). Systolic and diastolic blood pressure (SBP, DBP) were measured just before and 1, 2, 3, 4, 5, 7, 9, 12 and 24 hrs after treatment. Plasma nitrendipine concentrations were determined at 0.5, 1, 2, 3, 4, 5, 7, 9, 12 and 24 hrs and plasma catecholamines were measured at 2 and 5 hrs following drug administration. SBP did not decrease significantly after nitrendipine compared to after placebo at 9:00 AM or at 9:00 PM. DBP decreased significantly at 2, 3, 4 and 5 hrs after nitrendipine at 9:00 AM, but only at 4 hours after the 9:00 PM dose. Mean plasma nitrendipine concentrations during the absorption phase were lower after the evening dosage compared to the morning interval. Maximum plasma concentration (Cmax) was significantly lower and time to maximum concentration (tmax) tended to be longer after the evening dosage. Area under the plasma concentration-time curve from 0 to 24 hours (AUC0-24) and half-life of the terminal elimination phase (t1/2 beta) of the morning and evening dosages did not differ. A significant correlation was observed between plasma nitrendipine concentrations and changes in DBP during the drug treatment. Plasma noradrenaline concentrations were significantly higher 5 hours after nitrendipine compared to after placebo at 9:00 AM, but not at 9:00 PM.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Dose dependent effect of diltiazem on the pharmacokinetics of nifedipine.

The effect of diltiazem pretreatment on the pharmacokinetics of nifedipine were determined in six healthy male volunteers. Placebo or diltiazem (30 mg and 90 mg) was given orally three times daily for 3 days in a double-blind, Latin square method. On the fourth day, a 20-mg nifedipine was given orally 1 hour after the last dose of placebo or diltiazem. The mean elimination half-life of nifedipine prolonged significantly following diltiazem (2.54 hours on placebo vs 3.40 hours on 30 mg diltiazem and 3.47 on 90 mg diltiazem, both P less than .01). The mean AUC of nifedipine increased during diltiazem (1726.6 nmol X hr/ml on placebo vs 3838.0 on 30 mg diltiazem, and 5370.0 on 90 mg diltiazem, both P less than .05, 30 mg vs 90 mg, 0.1 less than P less than .05). The ratio of the AUC of primary metabolite (nitropyridine form) to the AUC of nifedipine was reduced by diltiazem pretreatment in a dose-dependent manner. ICG clearance was not influenced following diltiazem. These results indicate that diltiazem dose-dependently alters the pharmacokinetic profiles of nifedipine. The ICG clearance test showed that the liver blood flow did not decrease during diltiazem therapy, therefore, the reduction in the metabolic clearance of nifedipine might be caused by inhibiting effect of diltiazem on the activity of drug oxidizing enzymes.

Adult↗

Effects of H2-receptor antagonists on plasma aldosterone response to angiotensin II in healthy subjects; (II). Comparison of cimetidine and ranitidine.

The effects of H2-receptor antagonists, cimetidine and ranitidine, on plasma aldosterone response to angiotensin II (AII) were examined in six healthy subjects. The study was carried out on three different occasions with a two week interval. Cimetidine (400 mg), ranitidine (150 mg) or a placebo was given orally every 12 hours for 3 days in a double-blind, cross-over, double-dummy design. On the fourth day, 1 hour after the final (seventh) administration of the same agent, furosemide (20 mg) was injected intravenously. The plasma levels of renin activity (PRA), AII and aldosterone (PA) were determined for a 120 minute period after furosemide. PRA, AII and PA increased after furosemide with as well as without H2-receptor antagonist. The basal and stimulated levels of these parameters were not significantly different at any observation point among the three regimen groups. A significant correlation was observed between AII and PA with placebo (P less than 0.01) and ranitidine (P less than 0.01), but not with cimetidine (P greater than 0.05). The slope of the regression line with ranitidine was not significantly different from that of the placebo. These data indicate that the PA response to AII is blunted by cimetidine, but not by ranitidine. The current study supports the idea that this blunted response during cimetidine is independent of the blockade of H2-receptor.

Administration, Oral↗

Clinical pharmacology of dilevalol (I). Comparison of the pharmacokinetic and pharmacodynamic properties of dilevalol and labetalol after a single oral administration in healthy subjects.

Dilevalol (25 mg----50 mg----100 mg) or labetalol (100 mg) was given orally in six healthy subjects. The study was carried out on four occasions with a week interval. Blood samples for plasma drug concentrations were taken for a 24-hour post-drug period. Blood pressure (BP) as well as heart rate (HR) at supine position, during 50 degrees tilting and during a submaximal exercise were measured after each treatment. The mean maximum plasma concentration (Cmax) as well as the mean area under the plasma concentration-time curve (AUC) increased in a dose-dependent manner after dilevalol. These parameters after dilevalol 100 mg were significantly lower than after labetalol 100 mg. No significant differences were observed in the time to maximum concentration (tmax), the distribution half-life (t1/2 alpha) or the elimination half-life (t1/2 beta) between dilevalol and labetalol. There were no significant differences in BP at supine position or during 50 degrees tilting among the dosages. Postural changes in HR during 50 degrees tilting was significantly smaller after dilevalol 100 mg than following labetalol 100 mg. The suppressing effect of dilevalol 100 mg on an increase in HR during a submaximal exercise was significantly greater than during labetalol 100 mg. These data indicate that although plasma drug concentrations are lower after dilevalol than following labetalol, the beta-blocking activity of dilevalol is more potent than labetalol.

Administration, Oral↗

Clinical pharmacology of dilevalol (II). The pharmacokinetic, pharmacodynamic, and tolerance studies of dilevalol during repeated administration in healthy subjects.

Dilevalol (50 mg) was given orally twice daily for eight days in six healthy subjects. All parameters were obtained following 1st (on day 1) and 15th (on day 8) dosages. Blood samples for plasma drug concentrations were taken for a 12-hour (after 1st dosage) or a 24-hour (after 15th dosage) post-drug period. Blood pressure (BP) as well as heart rate (HR) at supine position, during 50 degrees tilting and during a submaximal exercise were measured after each dosage. The mean time to maximum concentration (tmax) was faster, and the mean area under the plasma concentration-time curve (AUC) was greater after 15th dosage than following 1st dosage. No significant differences were observed in the maximum plasma concentration (Cmax), the distribution half-life (t 1/2 alpha) or the elimination half-life (t 1/2 beta) between the two dosages. BP at supine position as well as during 50 degrees tilting decreased significantly after each dosage, and did not differ between 1st and 15th dosages. Postural changes in BP or HR during 50 degrees tilting were not induced following 1st or 15th dosage. The suppressing effects (%R) on an increase in HR during a submaximal exercise were significantly larger after 15th dosage than after 1st dosage. A significant correlation was observed between plasma dilevalol concentration and %R in HR. These data indicate that the hypotensive effect of dilevalol is not altered during the repeated administration of the drug for 8 days. However, the beta-blocking activity of dilevalol might be enhanced during the repeated dosages, which is, in part, attributed to dosage-dependent elevation in plasma drug concentrations.

Administration, Oral↗

Effect of diltiazem on the pharmacokinetics of propranolol, metoprolol and atenolol.

The pharmacokinetic interaction between diltiazem and three beta-adrenoceptor blockers propranolol, metoprolol and atenolol was investigated in healthy volunteers given diltiazem 30 mg or placebo t.d.s. for 3 days, followed by a single dose of propranolol 20 mg, metoprolol 40 mg or atenolol 50 mg. The AUCs of propranolol and metoprolol were significantly increased after diltiazem and it significantly prolonged the elimination half-life of metoprolol. In contrast, it did not significantly affect the pharmacokinetics of atenolol. Propranolol significantly decreased the resting pulse rate after diltiazem pretreatment as compared to placebo. The results indicate that diltiazem impaired the clearance of propranolol and metoprolol, which are principally metabolized by an oxidative pathway, and that the kinetic interaction between diltiazem and propranolol may partly be related to the significant reduction in the pulse rate produced by the latter.

Adult↗

Vertical transmission of human T-cell leukemia virus type I (HTLV-I): detection of proviral DNA in HTLV-I carrier gravida.

The seroprevalence rate of human T-cell leukemia virus type I (HTLV-I) in pregnant women in the Osaka district was determined by enzyme-linked immunosorbent assay and Western blot analysis. Twenty-one (1.0%) of 2192 samples tested were positive for both assays and the seropositive parturients were found to be integrated with HTLV-I proviral DNA in their mononuclear cells by a DNA dot blot hybridization assay using HTLV-I DNA probe or by a selective DNA amplification technique using the polymerase chain reaction (PCR). On the other hand, proviral DNA was not detected in cord blood of the neonates born to the carrier mothers, indicating that transplacental infection of HTLV-I during pregnancy could be excluded. The results support the hypothesis that postpartum infection via breast milk plays a significant role among the possible perinatal transmission routes.

Carrier State↗

I-protein forms cage-like aggregates of myosin in vitro.

I-protein was mixed with myosin before or after myosin filaments were reconstituted. In both cases, I-protein seemed to accelerate the myosin assembly. The binding of I-protein to myosin filaments was tested by sedimentation experiments and SDS-polyacrylamide gel electrophoresis. In a low ionic strength solution at pH 6.5, the binding ratio of I-protein to myosin was 1:40 by molar ratio when the I-protein molecules highly specifically bound to myosin filaments. I-protein could maximally bind to myosin filaments at the molar ratio of 1:2.7. In this case, excess I-protein molecules remained in the supernatant after sedimentation, although the unbound I-protein could still bind to myosin filaments. Electron microscopic observations revealed that I-protein bundled myosin filaments in the low ionic strength solution (pH 6.5). Cage-like structures which were very similar to the Mg-paracrystals of non-muscle myosins were formed at pH 7.2. In gel filtration, the apparent molecular mass of I-protein was 100 kDa, while it was 50 kDa in SDS gel electrophoresis. Therefore, I-protein is regarded to be a homodimer of a 50 kDa subunit and can divalently bind to myosin molecules.

Actin Cytoskeleton↗

Refined purification and characterization of Z-protein.

Using an improved procedure, Z-protein was prepared from myofibrils of chicken breast muscle. The yield of pure Z-protein increased to 10 mg per kg of muscle. The chain weight of Z-protein was 55,000 in the presence of SDS. However, Z-protein was eluted before aldolase (Mr 158,000) in Sephacryl S-400 column chromatography, and, therefore, it appeared to exist as a tetramer in a physiological salt solution. Z-protein had at least four isopeptides whose isoelectric points ranged from pH 6.0 to 6.4. Anti-Z-protein antiserum reacted equally with these isopeptides. The extinction coefficient of Z-protein at wavelength 278 nm was 4.2 (1%; light path, 1 cm). Z-protein which was purified according to this improved method did not bind to F-actin and alpha-actinin in a physiological salt solution.

Animals↗

Z-protein, a component of the skeletal muscle Z-line, is located at the apical tips of microvilli of chicken intestinal epithelial cells.

Antiserum against Z-protein, which is one of the components of myofibrillar Z-lines, strongly stained the epithelial cells of chicken small intestine at the apical tips of the microvilli and the junctional complexes. Immunoblot tests with anti-Z-protein antiserum showed that there is a peptide of the same antigenicity as myofibrillar Z-protein in the components of the epithelial cells of chicken small intestine. Hence it seems that the apical tip of the microvillus contains a constituent corresponding to the Z-protein of myofibrillar Z-line.

Actinin↗

Formation of the Photosynthetic Electron Transport System during the Early Phase of Greening in Barley Leaves.

The development of photochemical activity in isolated plastids during the early phase of greening of 5-day-old etiolated barley seedlings was studied and related to the appearance of chlorophyll-protein complexes. Photochemical activities of PSI (DCIPH(2) --> MV) and PSII (H(2)O --> DCIP, DPC --> DCIP) appeared at 1 and 1.5 hours after the onset of illumination, respectively. However, PSI + PSII activity (H(2)O --> MV, H(2)O --> NADP) appeared at 4 hours. The functional plastoquinone pool was noticed, at the latest, from 4 hours. Chloroplast preparations from seedlings of 1 h of greening showed O(2) uptake upon illumination in the absence of MV (-MV activity). This activity peaked at 2 hours of greening, then fell to zero by 6 hours. In contrast to the -MV activity, MV-Hill activity began to increase at 2 hours. Although PSI activity appeared at 1 hour, it failed to reduce ferredoxin until 2 hours. NADP began to be photoreduced at 4 hours in accordance with the appearance of the ferredoxin:NADP reductase activity. After formation of PSI and PSII, electron transport systems between them and between PSI and NADP developed in coordination with each other. Thus, the whole electron transport from water to NADP began to operate at 4 hours.

Journal Article↗

Effect of systemic and topical application of testosterone propionate on the density of epidermal Langerhans cells in the mouse.

Epidermal Langerhans cells (LCs) are bone marrow-derived immune cells in the epidermis. Recently, we reported that adenosine triphosphatase (ATPase)-positive LC density in the hind-limb skin of male mice was lower than that of female and that orchiectomy resulted in an increase in LC density, though ovariectomy had no significant effect. To further investigate the control mechanisms of sex differences in LC density, the effect of systemic and topical application of testosterone propionate (TP) on LC density was examined in C57BL/6 mice. Subcutaneous injections of TP 5.8 X 10(-8) mol (20 micrograms)/day/mouse for 14 d resulted in a significant decrease in LC density both in orchiectomized males and normal females, and such an effect was also observed in adrenalectomized mice, suggesting that this effect of TP is not indirectly mediated by glucocorticosteroids. TP was also effective when applied as an ointment (1% or 5%) to the right hind-limb skin of both orchiectomized males and normal females for 14 d; namely, the LC density of the right hind-limb was lower than that of the left. Beta-estradiol and progesterone 5.8 X 10(-8) mol/day/mouse had no significant effect on LC density when systemically applied for 14 d to normal males and females. These results suggest that sex differences in LC density may result from higher concentrations of testosterone or its metabolites in males, and that the function of testosterone may be local.

Administration, Cutaneous↗

Effects of non-shunting operation on azygos venous blood flow in cirrhotic patients.

Azygos venous blood flow and other haemodynamic parameters were measured in 14 cirrhotic patients to investigate the effects of a non-shunting operation, oesophageal transection with paraoesophagogastric devascularisation. Azygos venous blood flow measured by the local continuous thermal dilution method was significantly reduced by 13.8% after the operation (428 (41) v 369 (33) ml/min). Hepatic venous pressure gradient (HVPG) was also significantly decreased from 14.5 (0.8) to 12.8 (0.7) mmHg (-11.8%). Cardiac output and routine liver tests did not change remarkably postoperatively. In this haemodynamic study before and after non-shunting operation, moderate but significant decreases were seen in azygos venous blood flow and portal pressure (HVPG), without substantial changes in systemic circulation. This suggests that blood flow through the portosystemic collaterals other than oesophageal varices may be decreased but still adequate after the operation. Well preserved portosystemic collaterals without oesophageal varices are thus considered an optimally balanced state after non-shunting operation.

Adult↗

Ionophoretic activities of oligopeptide lactones and resin-glycosides in human erythrocytes.

Oligopeptide lactones (theonellapeptolides) isolated from the Okinawan marine sponge Theonella swinhoei and resin-glycosides (merremosides) from the tuber of an Indonesian medicinal plant Merremia mammosa were examined regarding their activities in transporting Na+, K+, and Ca++ ions into human erythrocytes. Each of these lactones, which had been shown, using a supported liquid membrane, to have an ionophoretic effect on the alkali metal ions, transported the ions to a different extent. The ion transporting activities of these compounds were completely lost when the macrocyclic lactone structures were cleaved by sodium methylate. Resin-glycosides with an additional branched glycosyl residue showed much greater ion transporting activities than those without it.

Erythrocytes↗

[General pharmacological studies on 5,8,11,14,17-eicosapentaenoic acid ethyl ester (EPA-E)].

EPA-E, even at 3,000 mg/kg, p.o., did not affect the general behaviors, spontaneous locomotor activities, pentobarbital hypnosis and body temperature; and it did not elicit anticonvulsant, analgesic and muscle relaxant actions. It had no influence on spontaneous EEG activities, even at 3,000 mg/kg, i.d. EPA-E at concentrations up to 10(-4) M, did not affect the tonus or agonist-induced contraction of the isolated ileum, trachea, fundus and vas deferens. EPA-E had no influence on the spontaneous movement of isolated ileum or uterus. EPA-E did not affect the nictitating membrane contraction and intestinal propulsive motility, and it did not damage gastric mucosa nor elicit antiulcer action. EPA-E at 1,000 mg/kg were without effect on gastric secretory volume (SV), total acidity (TA) and pepsin activities (PA). However, EPA-E at 3,000 mg/kg significantly decreased SV and TA without significantly decreasing PA. EPA-E caused no changes in the respiration, blood pressure, heart rate and ECG at the doses up to 3,000 mg/kg; and it did not affect the heart rate and contractile force on the isolated atria at concentrations up to 10(-4) M. The intracutaneous injection of 2.0% EPA-E produced neither anesthetic nor irritative action. EPA-E did not elicit hemolytic action at 10(-4) M. EPA-E, even at 3,000 mg/kg, did not affect the neuro-muscular transmission, urine volume, urinary excretion of electrolytes and carrageenin edema. These results suggested that EPA-E has no noticeable effects on the central nervous, autonomic nervous, respiratory and cardiovascular systems and so on.

Animals↗

Effect of physical exercise prelabyrinthectomy on locomotor balance compensation in the squirrel monkey.

This study examines the effectiveness of physical exercise, during a prepathology state, on locomotor balance compensation after subsequent unilateral labyrinthectomy in squirrel monkeys. An experimental group underwent 3 hr. of daily running exercise on a treadmill for 3 mo. prior to the surgery, whereas a control group was not exercised. Postoperatively, the locomotor balance function of both groups was tested for 3 mo. There was no significant difference in gait deviation counts in the acute phase of compensation. However, in the chronic compensation maintenance phase, the number of gait deviation counts was fewer in the exercise group, which showed significantly better performance stability.

Animals↗