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Biomedical subjects

K Ohashi

Publications and source records attributed to K Ohashi.

At least 451 records · Page 25Linked to original sources

Diurnal variation in the diuretic effects of nitrendipine in saline loaded rats.

We have previously reported that the responsiveness of blood pressure to nitrendipine, a dihydropyridine calcium antagonist, varies with its time of administration. The present study was undertaken to examine whether the diuretic effects of the agent also show diurnal variation. Nitrendipine was given orally at 12 a.m. or 12 p.m. to rats, and urine was collected for 8 hours after administration. The urine volume and urinary sodium excretion were greater at 12 p.m. than at 12 a.m. These data indicate that the cardiovascular as well as renal effects of nitrendipine vary with its time of administration.

Animals↗

Influence of chronic lithium treatment on urinary amount of furosemide in rats.

The present study was undertaken to examine whether the urinary amount of furosemide is influenced by chronic lithium treatment. LiCl at 2 mEq/kg/day in 1 ml vehicle (5% glucose solution) or 1 ml of vehicle alone was injected intraperitoneally for 8 days into Wistar rats. On day 8, 30 mg/kg of furosemide in 3% body weight of 1% NaCl was given orally, and urine was collected for 6 hr after dosage. The urinary amount of furosemide in the Li-treated rats was significantly lower than that in the control animals [Li group (n = 12): 514 +/- 75 (mean +/- S.E.) vs. control group (n = 12): 916 +/- 85 micrograms/kg/6 hr, P less than 0.01]. This finding indicates that pharmacokinetic alterations of furosemide might occur during chronic treatment with lithium.

Administration, Oral↗

Chronopharmacology of the new uricosuric diuretic S-8666 in rats: (II). Examination in aged rats.

We have previously demonstrated a time-dependent variability in the diuretic effects of S-8666, a new loop diuretic with uricosuric activity, in young rats. The present study was undertaken to determine whether such a daily variation in the effects of the agent exists in aged rats. S-8666 (30 and 90 mg/kg) was orally given at 12:00 a.m. (day trial) or at 12:00 p.m. (night trial) in young (10-11 week old) and aged (23-24 month old) Wistar rats. Urine was collected for 8 hours after the agent; and urinary excretions of sodium, S-8666 and its active metabolite S-8680 were determined. Urinary excretions of volume and sodium following S-8666 at 12:00 a.m. were greater than those at 12:00 p.m. in the young and aged animals. Urinary excretions of S-8666 and S-8680 were also greater in the day trial compared to those in the night trial in both groups of rats. In the day and night trials, there were significant correlations between urinary S-8666 + S-8680 and the diuretic effects in both groups of rats. These findings indicate that the diuretic effects of S-8666 also vary with its time of dosing in aged rats. The time-dependent variations in urinary S-8666 and S-8680 might be involved in this phenomenon.

Aging↗

Chronopharmacology of trichlormethiazide in rats: (III). Influence on serum triglyceride and glucose.

Trichlormethiazide was given orally to rats at 10 a.m. or 10 p.m. for 14 days. The diuretic effects of the agent at 10 a.m. were greater than those at 10 p.m. on day 14. Serum concentrations of triglyceride and glucose increased in both trials. The increments in these parameters were enhanced following trichlormethiazide at 10 a.m. These data indicate that the diuretic effects of trichlormethiazide and its untoward influences on serum metabolic parameters might vary with the administration time during a repeated therapy.

Animals↗

Influence of repeated administration of lithium on urinary excretion of prostaglandins in rats.

The present study was undertaken to examine whether urinary excretions of prostaglandins increase by repeated administration of a non-toxic dose of lithium. Our previous study demonstrated that 2 mEq/kg/day of lithium chloride (LiCl) is not a toxic dose; and therefore, this dose of LiCl in 1 ml vehicle (5% glucose solution) or 1 ml of vehicle alone was injected intraperitoneally for 7 days into Wistar rats. On day 7, 3% body weight of 1% NaCl solution was given orally; and urine for the determination of PGE2 and 6-keto-PGF1 alpha, a metabolite of PGI2, was collected for 6 hr after dosage. Thereafter, blood samples for measuring plasma renin activity (PRA) were obtained. The urinary amounts of PGE2 and 6-keto-PGF1 alpha in the Li-treated rats were significantly greater than those in the control animals. The values of PRA did not significantly differ between the two groups of rats. These findings indicate that the production of prostaglandins, including those of PGE2 and PGI2, are enhanced during repeated administration of a non-toxic dose of lithium. The enhanced production of prostaglandins might not be mediated through the activated renin-angiotensin system.

6-Ketoprostaglandin F1 alpha↗

Microvasculature of the tympanic membrane.

In order to investigate the blood flow of the tympanic membrane (TM) in various conditions, the microvasculature of the TM was observed by scanning electron microscope, using casting methods. Differences in vascular patterns between pars tensa and pars flaccida were observed, suggesting that vascular distribution in TM is closely concerned with the arrangement of radial fibers in the intermediate fibrous layer. Once inflammation was induced, changes in blood vessels quickly took place and most remarkably at the central zone of TM. The TM which closed earlier was found to leak resin at the edge of the perforation. It is proposed that an active blood flow to the perforation edge is necessary for a smooth closing.

Animals↗

[Phase I study of YM881 (zinostatin stimalamer) suspension by hepatic arterial infusion. Research Group for Intra-arterial Infusion Therapy with YM881].

A phase I study of YM-881 (zinostatin stimalamer), neocarzinostatin combined with butylesterified styrene maleate, suspended in iodized poppy oil ethyl ester, was conducted in patients with hepatocellular carcinoma by giving single intra-arterial infusions via catheters inserted by Seldinger's method. Four dose levels, 2, 4, 6, and 8 mg, were tested. Major adverse reactions were fever, anorexia, nausea, vomiting, and abnormal hepatic function. Both the incidence and severity of adverse reactions tended to increase with the 8 mg dose. Tumor regression of 50% or more occurred in one receiving 2 mg and one receiving 4 mg. The results of the study suggest that doses of 6 mg or less may be appropriate for the phase II studies.

Adult↗

The biosynthesis of thrombomodulin and its enhancement by dibutyryl cAMP in a human megakaryoblastic cell line, UT-7.

Thrombomodulin (TM) is an endothelial cell membrane glycoprotein which modulates coagulation via the formation of thrombin-TM complexes. We investigated the human megakaryoblastic cell line (UT-7) for the presence of functional TM on the cell surface and in cell lysates using a specific enzyme-linked immunosorbent assay, a functional assay, and analysis by fluorescent activated cell sorter. We also examined the effect of cyclic nucleotides on TM in UT-7 cells. Quiescent UT-7 cells contained TM protein in cell lysates, but no TM antigen was observed on the cell surface. Dibutyryl cyclic AMP up-regulated TM: UT-7 cells transiently expressed functional TM antigen on the cell surface via de novo synthesis of TM protein resulting from increased TM mRNA levels. In contrast, dibutyryl cyclic GMP did not significantly affect TM antigen levels. The results suggest that megakaryocytes produce TM antigen and protein kinase A are involved in cellular mechanisms of TM expression.

Bucladesine↗

[Phase II study of YM881 (zinostatin stimalamer) suspension injected into the hepatic artery. Research Group for Intra-arterial Injection Therapy with YM881].

A phase II study of YM 881 (zinostatin stimalamer) to determine the response and safety was conducted in patients with hepatocellular carcinoma by injecting a suspension of the drug into the hepatic artery. Repeated doses of 4 to 6 mg of the drug were given every 4 weeks so that the tumor tissues were filled with the suspension. Of the 195 registered patients, 15 were ineligible for the study, 8 dropped out, and data were missing for 5. A total of 167 patients completed the study. Response was assessed in the 167 patients who completed the study. CR was found in one, PR in 59, MR in 25, NC in 67, and PD in 15, with a response rate of 35.9. The safety of the drug was assessed in 177, excluding ineligible patients and 3 who dropped out because of the concurrent use of other drugs. Adverse reactions were found in 93.2% of the patients, and abnormal values in clinical laboratory tests in 60.5%. Major unwanted symptoms included fever, nausea, vomiting, and anorexia. Major abnormal changes in laboratory tests were elevated total bilirubin and LDH and abnormal hepatic function. About half the patients had malaise and pain related to the intra-arterial infusion therapy. The one year survival rate was 56.9%, and the duration of survival of 50% of the patients was 407 days.

Adult↗

Chronotherapeutic study of furosemide in hypertensive subjects: a preliminary report.

In the present study, circadian influences of furosemide on serum electrolytes, lipids and glucose were evaluated in ten hypertensive subjects. A retard capsule (40 mg) of furosemide was given once a day in the morning (07 h 00) or in the evening (19 h 00) for eight weeks. The study was done through a cross-over design. Twenty-four hour urine was collected, and fasting blood samples were obtained during the control period and at the end of each treatment period. The 24-hour urine volume was slightly increased by the repeated administration of furosemide in the morning and evening trials. Urinary excretion of sodium also slightly increased in the morning trial and significantly increased in the evening trial. Serum concentrations of potassium and chloride decreased, while serum uric acid and triglyceride were increased by furosemide treatment. No significant difference was observed in these parameters between morning and evening trials. Fasting blood glucose increased following furosemide. The increment in this parameter was greater in the evening trial than in the morning trial. These findings indicated that the influence of furosemide on glucose tolerance might vary with its time of administration.

Adult↗

Perinatal infection of human T-lymphotropic virus type I, the etiologic virus of adult T-cell leukemia/lymphoma. DNA amplification of specific human T-lymphotropic virus type I sequences.

A gene amplification technique, polymerase chain reaction, was used to detect human T-lymphotropic virus type I (HTLV-I), the etiologic agent of adult T-cell leukemia/lymphoma, in mononuclear cells in peripheral blood and breast milk of ten HTLV-I carrier gravida. The DNA in umbilical cord blood mononuclear cells of the neonates born to the HTLV-I carrier gravida were also amplified and examined for the possibility of HTLV-I infection via placenta during pregnancy. The HTLV-I sequences were detected both in the peripheral blood and milk of all ten carrier gravida by Southern blot analysis of amplified DNA. However, HTLV-I proviral DNA could not be detected in the cord blood of the carriers' neonates, indicating that transplacental infection of HTLV-I should be rare and that postpartum infection via breast milk is a likely major perinatal transmission route.

Antibodies, Neoplasm↗

Post-ischaemic treatment with the prostacycline analogue TTC-909 reduces ischaemic brain injury.

The effects of stable PGI analogue TTC-909 on CBF and glucose metabolism was studied in the chronic stage of cerebral ischaemia produced by occluding the distal MCA in SHRSP. Administration of TTC-909 (100 ng/kg/day during 7 days) prevented the development of ischaemic oedema and improved secondary metabolic derangement coupled to flow in postischaemic tissues, particularly in the ischaemic rim.

Animals↗

Circadian influence on effect of propranolol on exercise-induced tachycardia in healthy subjects.

Following a cross-over design propranolol 20 mg p.o. was given to 7 healthy subjects at 09.00 h and 21.00 h at an interval of 1 week. Heart rate (HR) during submaximal ergometer exercise was measured at four intervals during 10 h after treatment. Plasma propranolol concentrations were also determined. The suppressive effect (%R) of propranolol on the rise in HR during exercise after the morning dosage was significantly greater at 1.5 h and tended to be greater 3 h after administration than at comparable times in the evening trial. Mean plasma propranolol concentrations during the early phase were higher after the morning than the evening dose. The maximum plasma concentration (Cmax), area under the plasma concentration-time curve from 0 to 10 h (AUC (0-10] and absorption rate constant (ka) were significantly greater after the morning dose. The time to maximum concentration (tmax) and elimination half-life (t 1/2) of the morning and evening dosages did not differ. A significant correlation was observed between plasma propranolol concentration and %R in HR during exercise in the morning (r = 0.74) and evening (r = 0.63) trials, and the regression lines of the morning and evening treatments did not differ.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Melanocytes and melanosis of the oesophagus in Japanese subjects--analysis of factors effecting their increase.

Normal oesophagus specimens taken from 65 autopsy cases and surgical specimens from 127 oesophageal carcinoma cases were examined histopathologically to determine melanocyte incidence and distribution. Melanocytes were found in the epithelio-stromal junction in 7.7% of normal oesophagus specimens examined at autopsy, and in 29.9% of surgical cases with oesophageal carcinoma. Positive specimens in the latter groups, especially from pre-operatively irradiated individuals, showed a more remarkable increase of melanocytes than was evident in any of the normal oesophageal samples. There were no significant differences in incidence between males and females, or between age groups. In cases where the cancer invaded into deeper stroma, the melanocytes were mainly observed in the normal epithelium around the carcinomas. Epithelial and stromal elements of the melanotic mucosa commonly showed hyperplastic changes such as acanthosis or basal cell hyperplasia, and chronic oesophagitis. Melanocytes were observed most commonly in the lower part of the oesophagus, the site where malignant melanoma of the oesophagus, most often originates. These results strongly suggest that the melanocyte increase observed in areas of hyperplastic epithelium and chronic oesophagitis may play an important role as a precursor lesion for malignant melanoma in the oesophagus.

Asian People↗

Experimental transcatheter hepatic subsegmentectomy using absolute ethanol in dogs.

In this study, we evaluate the effect of an intraportal injection of absolute ethanol in the canine liver and discuss how to introduce it in clinical application. The intraportal injection of ten milliliters of ethanol using a balloon occlusion catheter created an evident and well-demarcated necrotic lesion in the right central lobe. Histological examination showed a typical coagulation necrosis with fibrous bands, which became thicker day by day. The weight of the necroses ranged from 5 to 55 grams with an average of 26.0 +/- 5.5 grams (mean +/- SE), which was approximately 20 to 40 per cent of the right central lobe. Complications resulting from the ethanol injection were minimal and although more studies need to be done to clearly establish its safety for cirrhotic patients with hepatoma, this technique may be an easier and less invasive substitute for operative hepatic subsegmentectomy.

Animals↗

Chronopharmacological study of furosemide; (VII). Influence of repeated administration on biochemical parameters in blood.

The present study was undertaken to examine whether influences of furosemide on biochemical parameters vary with its time of administration in Wistar rats. Rats were maintained under conditions of light (0700-1900 hrs) and dark (1900-0700 hrs). Furosemide (30 mg/kg) or vehicle (5% glucose) was given orally at 1000 hrs (day trial) or at 2200 hrs (night trial) for 14 days. Water and food intakes were measured, and urine was collected for 24 hours following the final dosage in each group. Thereafter, blood samples were obtained. Water intake and urinary excretions of volume, sodium and chloride increased by furosemide treatment. The increments in these parameters were greater in the day trial than in the night trial. Food intake did not change. The serum concentration of chloride was decreased by furosemide. The decrement in this parameter was enhanced in the day trial. The influence of furosemide on other biochemical parameters (sodium, potassium, creatinine, calcium, inorganic phosphate, total protein, total cholesterol and glucose) did not differ between the day and night trials. These data indicate that the untoward influence of furosemide on serum chloride might vary with its time of administration.

Administration, Oral↗