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Biomedical subjects

H Ohta

Publications and source records attributed to H Ohta.

At least 505 records · Page 28Linked to original sources
PubMed1991

Cardioprotective effects of KRN2391 and nicorandil on ischemic dysfunction in perfused rat heart.

The cardioprotective effect of KRN2391 (N-cyano-N-(2-nitroxymethyl)-3- pyridinecarboximidamide methanesulfonate), a novel vasodilator, was studied in the isolated perfused rat heart and compared with that of nicorandil. The isolated buffer-perfused rat heart was subjected to 25 min ischemia followed by 30 min reperfusion. The heart was pretreated with 0.1-10 microM KRN2391, 10-1000 microM nicorandil or vehicle. Before ischemia, KRN2391 (1-10 microM) and nicorandil (10-1000 microM) increased coronary flow, but did not modify the cardiac mechanical function. KRN2391 (1-10 microM) and nicorandil at high doses (300-1000 microM) resulted in significant improvements of cardiac functions and coronary flow during reperfusion and significantly reduced the release of cytosolic enzymes. The protective effects of 3 microM KRN2391 and 300 microM nicorandil were completely reversed by 3 microM glibenclamide, a blocker of ATP-sensitive potassium channels. Thus, KRN2391 and nicorandil at high doses have a direct cardioprotective effect, which may be related to activation of ATP-sensitive potassium channels.

Animals↗
PubMed1991

Non-enzymic glycation of human extracellular superoxide dismutase.

The secretory enzyme extracellular superoxide dismutase (EC-SOD) is in plasma heterogenous with regard to heparin-affinity and can be divided into three fractions, A that lacks affinity, B with intermediate affinity and C with high affinity. The C fraction forms an equilibrium between the plasma phase and heparan sulphate proteoglycan on the surface of the endothelium. In vitro EC-SOD C could be time-dependently glycated. The enzymic activity was not affected in glycated EC-SOD, but the high heparin-affinity was lost in about half of the studied glycated fraction. Addition of heparin decreased the glycation in vitro, and EC-SOD C modified with the lysine-specific reagent trinitrobenzenesulphonic acid could not be glycated in vitro. The findings suggest that the glycation sites are localized rather far away from the active site and may occur on lysine residues in the heparin-binding domain in the C-terminal end of the enzyme. The proportion of glycated EC-SOD in serum of diabetic patients was considerably higher than in normal subjects. Of the subfractions, EC-SOD B was by far the most highly glycated, followed by EC-SOD A. EC-SOD C was glycated only to be a minor extent. The findings suggest that glycation is one of the factors that contribute to the heterogeneity in heparin-affinity of plasma EC-SOD. Since this phenomenon is increased in diabetes, the cell-surface-associated EC-SOD may be decreased in this disease, increasing the susceptibility of cells to superoxide radicals produced in the extracellular space.

Chromatography, Gel↗
PubMed1991

Specific cholinergic destruction in the basal magnocellular nucleus and impaired passive avoidance behavior of rodents.

A nerve growth factor (NGF)-diphtheria toxin conjugate (NGDT) was found to selectively abolish or depress the activity of NGF receptor-bearing cholinergic neurons of the basal magnocellular nucleus (BMN). Bilateral cortical injections of NGDT impaired the retention of passive avoidance behavior in mice. A memory deficit was also revealed when cortical injections of NGDT were administered after the acquisition of a passive avoidance response. Thus, retrograde destruction of BMN cholinergic neurons by the cortical injection of NGDT interfered with both learning and memory processes. The animal model outlined here should be useful in analyzing the pathogenesis of Alzheimer's disease and the functions of the cholinergic system in the BMN.

Animals↗
PubMed1991

Search for polynuclear pentavalent technetium complex of dimercaptosuccinic acid [Tc(V)-DMS] tumour localization mechanism. I. Medullary thyroid carcinoma animal model.

To search for the tumour localization mechanism of Tc(V)-DMS, a polynuclear pentavalent technetium complex of dimercaptosuccinic acid [Tc(V)-DMS], the development of medullary thyroid carcinoma (MTC) bearing mouse model was considered. Subcutaneously transplanted tumour was allowed to grow for 2, 4 and 6 weeks, and the influence of the tumour stage on the biodistribution of Tc(V)-DMS was screened. High radioactivity uptake in the tumour tissue was observed, and this accumulation showed a direct correlation with tumour growth and calcitonin secretion, the MTC marker detectable in the blood serum. The gathered data implicated some calcitonin-related factors as the mediator in the Tc(V)-DMS localization; participation of a phosphate-like oxoanion, TcO4(3-), is strongly suggested not only by the high radioactivity accumulation in the calcitonin-producing tumour but also by the accumulation in the bones of this model animal.

Animals↗
PubMed1991

Pharmacokinetics of SUN 1165, a new antiarrhythmic agent, in renal dysfunction.

The pharmacokinetics of a new Class I antiarrhythmic agent, SUN 1165, has been studied in 32 patients with varying degrees of renal impairment following a single oral dose of 50 mg. The apparent volume of distribution at steady state was 1.48 l.kg-1, the absorption rate constant was 2.2 h-1, and plasma protein binding was 26.8% in subjects with normal renal function. These variables were not altered with renal impairment. More than 60% of SUN 1165 given orally was excreted unchanged via the kidney, both by tubular secretion and glomerular filtration. The elimination rate constant, the apparent total body clearance and the apparent renal clearance were linearly correlated with the endogenous creatinine clearance. The half-time of elimination was 3.4 h in normal subjects and it was prolonged to 23.7 h in severe renal failure (creatinine clearance below 20 ml.min-1.1.48 m-2). Dosage adjustment of SUN 1165 is necessary in renal failure.

Acute Kidney Injury↗
PubMed1991

Liver atrophy after transcatheter arterial embolization and percutaneous ethanol injection therapy for a minute hepatocellular carcinoma.

A 63-year-old male patient with compensated cirrhosis underwent transcatheter arterial embolization (TAE) and percutaneous ethanol injection therapy (PEIT) for a minute hepatocellular carcinoma (HCC). Although the HCC was successfully treated, esophageal varices worsened and refractory ascites developed 3 months after the TAE and PEIT. Liver atrophy progressed rapidly compared to the natural course of liver cirrhosis.

Atrophy↗
PubMed1991

Gastrointestinal absorption of cadmium and metallothionein.

Intestinal uptake and transport of cadmium (Cd) to different organs were studied in control and oral zinc pretreated rats using an in situ intestinal loop model. Intestinal loop was incubated with either CdCl2 or Cd-metallothionein (Cd-MT) for 30 and 60 min in rats under anesthesia. Induction of MT by oral Zn pretreatment had little effect on intestinal uptake of Cd ion. However, when intestinal loop was incubated with exogenous Cd-MT, the uptake of Cd was significantly smaller than that from CdCl2 incubation. About 50% of the Cd in the intestine of control rat after CdCl2 incubation was recovered in the cytosol fraction and bound to high-molecular-weight (greater than 60 kDa) proteins. In both Zn pretreated rats incubated with CdCl2 and control rats incubated with Cd-MT, Cd was mostly recovered in the intestinal cytosol fraction (75-85%) and was mainly bound to MT. After 60 min incubation of control intestinal loop with CdCl2. Cd was detected mainly in liver with small amounts in kidney and pancreas: with Cd-MT incubation, Cd was detected only in the kidney. The deposition of Cd in the liver was markedly decreased by Zn pretreatment. Both the uptake of Cd-MT by intestine and the induction of MT synthesis in the intestine by Zn pretreatment were demonstrated by immunohistochemistry using a specific antibody to rat liver MT. The results suggest a slow uptake of exogenous Cd-MT from the intestine and transport to kidney in contrast to deposition of Cd in the liver from CdCl2. Although the intracellular presence of MT does not affect the uptake of Cd from lumen, it may decrease both the release of Cd from the intestine and its deposition in liver.

Animals↗
PubMed1991

Apparent enhancement by SCH 23390 of apomorphine-induced locomotor activity in mice.

Effects of the dopamine (DA) D1 antagonist SCH 23390 and the DA D2 antagonist (-)-sulpiride on apomorphine-induced characteristic changes in spontaneous motor activity were investigated in mice using the system we have devised for automatically analyzing animal behaviors in mice. Apomorphine (3 mg/kg, SC) markedly increased parameters of spontaneous motor activity such as locomotor activity and rearing time. Apomorphine-induced increase in locomotor activity had peaks at 5-20 and 30-50 min after administration, and its trough was closely related to the marked increase in rearing time induced by this agonist. Apomorphine-induced locomotor activity accumulated over a 40-min period from 5 to 45 min after apomorphine injection, during which apomorphine-induced increase in rearing time peaked, was significantly increased by intraperitoneal administration of 0.03 and 0.1 but not 0.01 mg/kg SCH 23390. Apomorphine-induced increase in rearing time was dose-dependently depressed by this antagonist. In contrast, (-)-sulpiride (10-40 mg/kg, IP) decreased apomorphine-induced increases in rearing time and locomotor activity rather than enhancing the latter parameter. These data suggest that the apparent enhancement by SCH 23390 of apomorphine-induced locomotor activity is mediated through DA D1 receptors and does not always correlate with depression of apomorphine-induced rearing behavior in mice.

Animals↗
PubMed1991

Desipramine enhances isolation-induced aggressive behavior in mice.

Effects of desipramine on aggressive behavior induced by long-term (6-7 weeks) isolation of mice were examined. Aggressive behavior was measured as duration of biting attack and/or wrestling during a 20-min observation period. Desipramine (5, 10 and 20 mg/kg, IP) and imipramine (10 and 20 mg/kg, IP) dose-dependently increased the duration of aggressive behavior in isolated mice, without inducing aggressive behavior in group-housed animals. Desipramine-induced increase in aggressive behavior was blocked by phentolamine (3 mg/kg, IP) and yohimbine (0.3 mg/kg, IP), but not prazosin (0.5 mg/kg, IP). Clonidine (0.001 mg/kg, IP), an alpha 2 agonist, significantly blocked desipramine-induced enhancement of aggressive behavior in isolated mice without affecting the basal aggression. These data suggest that long-term isolation may induce functional changes in the sensitivity of alpha 2 receptor in the noradrenergic system and that desipramine enhancement of aggressive behavior in isolated mice is modulated by drugs acting onto alpha 2 noradrenergic receptors.

Aggression↗
PubMed1991

Effects of forced shaking stress at low temperature on pentobarbital-induced sleeping in mice.

1. Effects of a new stressful manipulation, forced shaking stress at low temperature (4 degrees C) (FSLT stress), on sleeping induced by pentobarbital were investigated 70 min following its application. 2. Repeated application (7 times) decreased the duration of sleep induced by pentobarbital-Na (45 mg/kg, i.p.) in mice without affecting that induced by ketamine-HCl and chloral hydrate. This effect of FSLT stress disappeared 3 days after termination of application. 3. The latency of nociceptive response in hot-plate test increased in a naloxone-sensitive manner by single and repeated FSLT stress when tested immediately (2 min) after but not 70 min after the last stress application. 4. Diazepam (0.3 mg/kg, i.p.) significantly prolonged the duration of sleep induced by pentobarbital (45 mg/kg, i.p.) in stressed animals without changing that in unstressed animals. The effect of diazepam was blocked by Ro 15-1788 (10 mg/kg, i.p.), a specific benzodiazepine receptor antagonist. 5. Repeated FSLT stress thus appears to decrease pentobarbital sleep by inducing functional changes in the central nervous system and the GABAergic system may partially participate in FSLT stress-induced decrease in pentobarbital sleep.

Animals↗
PubMed1991

Cardiovascular changes induced by chemical stimulation of the amygdala in rats.

The role of the amygdaloid complex in the central regulation of the cardiovascular system was studied in unanesthetized, unrestrained rat. The injection of carbachol into the amygdaloid complex elicited a pressor response, whereas the injection of noradrenaline and 5-hydroxytryptamine into the same area caused no significant cardiovascular changes. The greatest pressor response was obtained when carbachol was injected into the central nucleus. Bradycardia and tachycardia occurred when injection of carbachol was made into dorso-central and medio-ventral parts of the amygdaloid complex, respectively. Concomitant with cardiovascular responses, the injection of carbachol into the amygdaloid complex produced behavioral changes including immobilization, body shaking, searching and rearing. The pressor response and bradycardia were suppressed by prior local injection into the amygdaloid complex of atropine but not hexamethonium. These results suggest that the cholinergic system mediated by activation of muscarinic receptors in the amygdaloid complex may play a role in the control of cardiovascular and autonomic function.

Amygdala↗
PubMed1991

Analysis of gastric carcinoma growth by endoscopic ultrasonography.

Endoscopic ultrasonography (EUS) was performed preoperatively in 82 patients with gastric carcinoma (40 with early and 42 advanced malignancy). Measurements of wall thickness were performed in each case and showed good correlation with histological findings. Wall thickening was found to consist of both tumorous and accompanying ulcerous tissue. Thus, increasing wall thickness, as demonstrated by EUS, may not necessarily mean progressive tumor growth. The EUS features of gastric carcinoma were analyzed and four distinct growth patterns found: predominantly intramural (IM) or intraluminal (IL) growth with preservation (Type 1) or destruction (Type 2) of the submucosal echo-rich layer. All early carcinomas displayed the IL-type growth pattern on EUS (98% IL1-type) and 81% of advanced tumors showed IM-type features. EUS was able to differentiate between early and advanced carcinoma in 98% of cases. The EUS pattern of submucosal destruction (type IM2 or IL2) corresponded to the expanding type tumor according to Ming's histopathological classification. On the other hand, 24 of 26 infiltrative tumors according to Ming were found on EUS to have an intramural growth pattern with preservation of the submucosa (type IM1). It is concluded that EUS is highly sensitive in predicting the tumor growth pattern in gastric carcinoma, providing important additional information to the currently used TNM staging system. Measurements of wall thickness are reliable but differentiation between tumorous growth and peritumorous changes is not possible.

Carcinoma↗
PubMed1991

Tc-99m(V) DMSA uptake in cardiac amyloidosis.

Tc-99m(V) DMSA scintigraphy was performed on two patients with primary cardiac amyloidosis. Scintigraphy performed (after radionuclide administration) showed accumulation in the myocardium.

Amyloidosis↗