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Biomedical subjects

A Akashi

Publications and source records attributed to A Akashi.

At least 73 records · Page 4Linked to original sources
PubMed1987

Studies on the antihypertensive properties of carvedilol, a compound with beta-blocking and vasodilating effects.

The purpose of this study was to examine the antihypertensive effect of carvedilol and the possible mode of its action. After single oral administration, carvedilol (3-30 mg/kg) produced dose-related decreases in systolic blood pressure (SBP) and heart rate in conscious hypertensive models: spontaneous hypertensive rats (SHR), renal hypertensive rats (one kidney, one clip), and deoxycorticosterone acetate (DOCA)/salt rats. Repeated administration of carvedilol (10 mg/kg, p.o., once daily for 5 days) caused a fall in SBP and bradycardia in SHR. The development of tolerance and the rebound phenomenon of SBP were not seen. In anesthetized SHR, the hypotensive response to carvedilol (0.3 mg/kg, i.v.), unlike that to propranolol, was accompanied by a significant reduction of total peripheral resistance. A tendency toward a decrease in plasma renin activity was observed after oral carvedilol in SHR. The hypotensive effect was not attenuated by the pretreatment of SHR with indomethacin. Further, carvedilol did not cause appreciable changes in the production of 6-ketoprostaglandin (PG) F1 alpha in the aortic rings of SHR. In anesthetized cats, carvedilol (0.1 mg/kg, i.v.) produced a significant decrease in blood pressure but the same dose in the cerebral ventricle caused no detectable fall in blood pressure. The significant fall in blood pressure was observed in both intact and debuffered cats. These results suggest that carvedilol may possess a broad hypotensive spectrum against various types of experimental hypertension, and that the endogenous PG system and the central cardiovascular control system may not be responsible for the antihypertensive effect of carvedilol.

Administration, Oral↗
PubMed1986

[Effect of an antihypertensive drug, budralazine, on glucose and lipid metabolism in diabetic SHR].

Budralazine was evaluated for its effects on glucose and lipid metabolism in diabetic SHR. SHR treated with 10% sucrose solution as drinking water for 3 months exhibited an impaired glucose tolerance with higher serum insulin levels and a reduction of sigma delta IRI/sigma delta BS. This model was, therefore, considered to resemble hypertensive patients with non-insulin-dependent diabetes (NIDD). Streptozotocin (30 mg/kg, i.v.)-treated SHR had a glucose intolerance with lower serum insulin levels and a reduction of sigma delta IRI/sigma delta BS, suggesting a similarity to hypertensive states with insulin-dependent diabetes (IDD) in humans. Repeated administration of budralazine (15-60 mg/kg/day, p.o.) had no effect on glucose tolerance, insulin secretion, serum electrolytes and lipid levels in Wistar rats, SHR, IDD-SHR and NIDD-SHR. Budralazine caused a significant decrease in systolic blood pressure in IDD-SHR and NIDD-SHR as well as in SHR. Repeated administration of furosemide (50-100 mg/kg/day, p.o.) resulted in a marked reduction in glucose tolerance, sigma delta IRI/sigma delta BS and serum potassium in Wistar rats. These effects of furosemide were more pronounced in SHR and IDD-SHR (IDD-SHR greater than SHR) and were reduced by either KC1 supplement or administration of triamterene. Thus, furosemide-induced glucose intolerance seems, at least partially, to be attributed to potassium loss which led to decreased insulin secretion. From these results, it is possible that budralazine may be useful for the treatment of hypertensive patients with diabetes.

Animals↗
PubMed1986

[Effect of an antihypertensive drug, budralazine, on the cerebral circulation in spontaneously hypertensive rats].

Budralazine was evaluated for its effect on the cerebral blood flow (CBF) in comparison with some antihypertensive drugs in spontaneously hypertensive rats (SHR). The oral doses for each drug were selected to reduce arterial blood pressure to near normotensive levels. Equihypotensive rats were also produced by a controlled-hemorrhage and used as a control group. The blood flows in the parietal cortex and caudate nucleus were measured using the hydrogen clearance method at the time points when the pressure levels averaged about 120 mmHg after administration of each of the drugs or controlled-hemorrhage. Budralazine (40 mg/kg) significantly increased the regional CBF by approximately 60% with a significant decrease in the cerebral vascular resistance. A similar effect was also observed with hydralazine (9 mg/kg). The CBF-increasing effect of nifedipine (7 mg/kg) was less potent than that of budralazine. Neither prazosin (6 mg/kg) nor alpha-methyldopa (1,000 mg/kg) increased the regional CBF. Such cerebrovascular responses were also observed with controlled-hemorrhage. Furthermore, budralazine given intravenously (3-10 mg/kg) caused a significant and dose-dependent increase (50-250%) in the regional CBF without affecting the arterial blood pressure. This effect of budralazine was partially attenuated by the pretreatment with either reserpine or 6-hydroxydopamine. It is possible that catecholaminergic control of cerebrovascular tone is at least in part involved in the mechanism whereby budralazine increases the CBF.

Animals↗
PubMed1985

Effects of 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (platelet activating factor) on cardiac function in perfused guinea-pig heart.

The direct cardiac action of 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (PAF) was studied in isolated perfused guinea-pig heart preparations. PAF produced a fall in left ventricular pressure, decreases in the rate of rise of the left ventricular pressure (dp/dt) and coronary flow, but had no effect on heart rate. These results indicate that PAF is a cardiodepressant with inotropic selectivity and this effect on heart is blocked by CV-3988, a specific PAF antagonist.

Animals↗
PubMed1985

Effect of timiperone, a new antipsychotic drug, on the sleep-wakefulness cycle in cats.

The effect of timiperone, a new antipsychotic drug, on the sleep-wakefulness cycle in cats was assessed by EEG, EMG and eye movement potential. Timiperone (0.03 to 0.3 mg/kg, i.p.) dose-dependently increased the slow wave sleep (SWS) time and decreased the paradoxical sleep (PS) time. Further, the onset of the first period of PS was delayed, and the number of PS phases tended to be decreased after the 0.3 mg/kg dose. These results suggest that the neurological control of the cerebral dopaminergic system might be at least in part attributable to the effect of timiperone on sleep mechanisms.

Animals↗
PubMed1985

[Surgical therapeutic planning for non-small cell lung cancer].

The survival rates of 380 resected cases of lung cancer in our hospital were analyzed according to curability and histological cell type. The overall 5-year survival rate for stage I a cases was 64.5%, that for stage I b 52.3%, and that for stage II 26.7%. However, there were distinct differences in survival rates between stages I a-II with mediastinal lymph node dissection and those without mediastinal lymph node dissection. Of these 380 tumors, many were advanced (for instance, stage III tumors comprised 180 cases). T3 tumors had better prognosis (40.7% showing 5-year survival) than N2 tumors (26.7% showing 5-year survival). Among stage III tumors, squamous cell carcinoma (T3: 41%, N2: 36.7% showing 5-year survival) had a better prognosis than adenocarcinoma (T3: 16.1%, N2: 21.4%). T3N2 tumors, however, had such a poor prognosis that the value of surgery in these cases seemed questionable. Adjuvant therapy should therefore be evaluated accurately in future to improve prognosis. It was stressed that a randomized controlled study would be needed to evaluate the effectiveness of adjuvant therapy.

Adenocarcinoma↗
PubMed1985

Changes in duodenal mucosal blood flow and mucus glycoprotein content during cysteamine-induced duodenal ulceration in rats.

The effects of cysteamine on duodenal mucosal blood flow and duodenal glycoprotein were studied during the development of duodenal ulceration in conscious rats. Cysteamine at an ulcerogenic dose (300 mg/kg s.c.) produced a remarkable decrease of duodenal mucosal blood flow which preceded the appearance of duodenal ulcers. The reduced blood flow was followed by a significant decrease of tissue levels of glycoprotein which also occurred prior to the time when duodenal injury had reached a maximum. Cysteamine was without significant effect on the rate of incorporation of 3H-glucosamine into duodenal glycoprotein at concentrations up to 10(-3) M. These results suggest that the reduction in duodenal mucosal blood flow in response to cysteamine could possibly contribute to a decrease of duodenal glycoprotein and that both may be at least in part responsible for the incidence of duodeno-ulcerogenecity.

Animals↗
PubMed1984

[Experimental cerebral ischemia after bilateral common carotid artery ligation in SHRSP, SHRSR and Wistar rats: correlation between blood pressure and degree of ischemia].

Three different pressure groups of rats, stroke-prone spontaneously hypertensive rats (SHRSP, 200-270 mmHg), stroke-resistant SHR (SHRSR, 160-240 mmHg), and Wistar rats (WR, 120-160 mmHg) were used to investigate the effect of prior existing hypertension on the severity of brain damage induced by ischemia. The cerebral ischemia was induced by bilateral common carotid artery ligation (BLCL) and the survival rate, cerebral blood flow, cerebral energy metabolites (ATP, lactate c-AMP) and water content were measured. Colloidal carbon perfusion was also performed. Sixteen-week-old male rats were used. The survival rate was observed until 24 hours after BLCL. Cerebral blood flow was measured in parietal cortex by hydrogen clearance method. ATP was measured by luciferin-luciferase method, and lactate by enzymatic method using LDH. c-AMP was measured by radioimmunoassay. Brain water content was measured by freeze-dry method. These measurements were done for animals surviving 6 hours of BLCL. Colloidal carbon perfusion was done according to Ames' Method. The survival rate was lower in the hypertension group. The survival of SHRSP and SHRSR were 20% compared to 71% in WR after 24 hours of BLCL. The cerebral circulation of SHRSP fell abruptly and was near to zero after one hour of BLCL. In SHRSR this fall of cerebral blood flow was prominent in the rats of higher blood pressure. On the other hand there was no apparent fall of cerebral blood flow in WR after BLCL. The cerebral energy metabolites. ATP and c-AMP showed the lowest level in SHRSP which had the negative correlation to blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1984

[An electroencephalographical study on timiperone, a new antipsychotic drug].

This investigation was undertaken to analyze the EEG synchronizing effects of timiperone in cats. The effects of timiperone on the brain-stem reticular and hypothalamic activating system, diffuse and specific thalamic projection system, and caudate spindle were investigated by the electroencephalographic method. Timiperone produced a weak inhibition of EEG arousal response induced by electrical stimulation of the sciatic nerve almost without affecting that which was induced by stimulation of the mesencephalic reticular formation. Furthermore, timiperone suppressed the activation of neocortical EEG in response to stimulation of the posterior hypothalamus more selectively than that of limbic EEG. Neither the recruiting response to stimulation of the centro-median nucleus of the thalamus nor the augmenting response to stimulation of the ventro-postero-lateral nucleus of the thalamus was modified by timiperone. In addition, timiperone significantly potentiated the caudate spindle. The EEG effects of haloperidol were qualitatively similar to those of timiperone. These results indicate that the synchronizing effect of timiperone may be mediated by a suppression of an ascending reticular activating system and may influence the conscious levels and sleep-wakefulness cycle in cats.

Animals↗
PubMed1984

Dulcerozine-induced duodenal ulcers in rats: a simple, highly-reliable model for evaluating anti-ulcer agents.

Dulcerozine-induced duodenal ulcers in rats were studied in order to establish the optimum conditions for a routine production of ulcers and to elucidate their possible pathogenesis. Single doses of dulcerozine administered either subcutaneously or orally produced a dose-related duodenal ulceration in rats. The ulcerogenic effect of dulcerozine was most potent when given subcutaneously to 24-hr fasted animals at 300 mg/kg. At this dose, deep or perforating ulcers were consistently produced within 18 hr, but mortality due to general toxicity of the agent was excluded at least up to 48 hr. Feeding of animals resulted in a significant reduction in susceptibility to dulcerozine. An antacid and antisecretory agents prevented dulcerozine-induced duodenal ulceration in a dose-dependent manner. Either pylorus ligation or vagotomy completely inhibited duodenal ulceration in response to dulcerozine. In addition, an ulcerogenic dose (300 mg/kg s.c.) of dulcerozine evoked a sustained gastric hypersecretion in pylorus ligated rats. These results suggest that a stimulating action on gastric secretion may be, at least in part, responsible for the ulcerogenic property of dulcerozine. The present study provides a new reliable model for investigations of the pathogenesis and therapy of duodenal ulcer disease.

Animals↗