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S Ashida

Publications and source records attributed to S Ashida.

At least 37 records · Page 2Linked to original sources
PubMed1992

Effects of the new cognition-enhancing agent nefiracetam in rats with cerebral embolism.

The effects of nefiracetam (DM-9384, CAS 77191-36-7) on the learning behavior and cholinergic and GABAergic neuronal transmitter systems of rats with experimentally-induced cerebral embolism were investigated. Cerebral embolisms were induced in male Wistar rats by injection of 800 microspheres 50 microns in diameter via the left internal carotid artery under 2% halothane anesthesia. Daily oral administration of nefiracetam (30 mg/kg/d) was started 9 days after embolization. Nefiracetam caused significant (p < 0.05) improvement of deficits in the learning of both water maze and passive avoidance tasks beginning 22 days after embolization of the rats. The drug also significantly restored decreases in cortical choline acetyltransferase (p < 0.05) and hippocampal glutamic acid decarboxylase activities (p < 0.01) in the embolized cerebral hemisphere and significantly increased cortical choline acetyltransferase (p < 0.05) and acetylcholinesterase activities (p < 0.05) in the contralateral cerebral hemisphere 21 days after embolization. These results demonstrate that nefiracetam improves cognitive dysfunction in the late phase in embolized rats and suggest that the effect is at least partly due to the increase in glutamic acid decarboxylase, choline acetyltranseferase and acetylcholinesterase activities.

Acetylcholinesterase↗
PubMed1991

A thromboxane A2 synthase inhibitor, DP-1904, prevents rat renal injury.

The effects of DP-1904, a thromboxane (TX) A2 synthase inhibitor, on renal function were investigated by analysis of prostanoid metabolism in hydronephrotic and ischemic rat kidney models, and in isolated perfused normal and hydronephrotic rat kidneys. The increase in production of TXB2 in hydronephrotic or ischemic kidneys was significantly suppressed by intraperitoneal DP-1904 (10 mg/kg), with the 6-keto-prostaglandin F1 alpha to TXB2 ratio being significant increased. Urine volume, glomerular filtration rate and renal plasma flow were all improved. DP-1904 (0.3 micrograms/min) blocked the effects of infused arachidonic acid on isolated perfused normal rat kidneys thus reducing TXB2 levels and perfusion pressure but the pressor response to norepinephrine or angiotensin II remained unchanged. In isolated perfused hydronephrotic rat kidneys, DP-1904 suppressed the increase in perfusion pressure and TXB2 production caused by platelet-activating factor. These findings suggested that DP-1904 improved renal failure by specifically inhibiting TXA2 production.

6-Ketoprostaglandin F1 alpha↗
PubMed1991

Production and localization of enzymes on soft gel cultivation.

Production and localization of glutaminase and leucine aminopeptidase (LAP) in soft gel cultivation were compared with those in koji and liquid cultivations. The enzymes were detected only in the whole-mycelial-mat fraction by soft gel cultivation, but in both intracellular and extracellular fractions by the other two methods. The enzyme species of glutaminase and LAP in soft gel cultivation were analyzed by ion exchange and gel filtration column chromatographies. Three species of glutaminase and four (or five) species of LAP were formed in the whole-mycelial-mat fraction. The intracellular and extracellular fractions of the koji and liquid cultivations contained different species of enzymes.

Agar↗
PubMed1990

Role of platelets as a factor aggravating cerebral ischemia.

In order to clarify the role of platelets as a factor aggravating cerebral ischemia, an experimental model of ischemia was investigated using thrombocytopenic rats. In addition, the prostacyclin derivative (OP-41483) and the thromboxane A2 synthetase inhibitor (OKY-046), both of which inhibit platelet aggregation, were tested for possible beneficial effects on cerebral ischemia. Cerebral ischemia was produced in spontaneously hypertensive male rats using bilateral common carotid artery ligation (BLCL). Thrombocytopenia was produced with an antiplatelet antiserum which reduced the platelet count to less than 6 x 10(4)/microliters by 24 h. OP-41483 was administered four times hourly (500 ng/kg x 4, i.p.), beginning 1 h prior to BLCL. Similarly, OKY-046 was injected four times hourly (10 mg/kg x 4, i.p.). Brain metabolites such as ATP, lactate and pyruvate and water content were determined after 3 h of cerebral ischemia. Brain levels of ATP in the ischemic rats with thrombocytopenia were higher than those of the ischemic rats without thrombocytopenia. In addition, thrombocytopenia reduced the increase of lactate and water content in the ischemic brain. Animals treated with OP-41483 also maintained higher levels of ATP and lower levels of lactate and water compared to animals given a vehicle. OKY-046 significantly reduced brain water content, but had no effect on the ischemic alteration of brain metabolite levels. These results indicate that platelets play an important role in the progression of metabolic change during ischemia.

Adenosine Triphosphate↗
PubMed1990

Effects of antihypertensive drugs on experimental cerebral ischemia in spontaneously hypertensive rats.

The effects of antihypertensive drugs on ischemic cerebral damage were investigated using the bilateral carotid artery occlusion (BCAO) model in SHR. Oral budralazine and nifedipine, at doses that increased cerebral blood flow (CBF) in SHR in our previous study (Tanaka, S. et al., Folia Pharmacol, Japan, 87, 1986), significantly improved cerebral energy failure after the BCAO, but prazosin which does not increase CBF had no effect on the energy failure. These results suggest that the amelioration by these antihypertensive drugs of the energy failure after the BCAO results from its CBF-increasing effects in SHR.

Adenosine Triphosphate↗
PubMed1990

Uricosuric and diuretic activities of DR-3438 in dogs and rabbits.

The purpose of this study was to evaluate the uricosuric and diuretic properties of the new diuretic agent DR-3438. In the conventional clearance studies in urate-loaded dogs, intravenous injection of DR-3438 (3-30 mg/kg) resulted in dose-related increases in fractional excretion of urate (FEua), urine flow and sodium excretion. At doses causing similar natriuresis, tienilic acid (50 mg/kg, i.v.) markedly increased the FEua value, whereas indacrinone (1 mg/kg, i.v.) had no significant effect on it. Trichloromethiazide (1 mg/kg, i.v.) and furosemide (0.3 mg/kg, i.v.) tended to decrease the FEua. Thus, the uricosuric activity of DR-3438 (30 mg/kg) was 0.6-fold that of tienilic acid and 3.4-fold that of indacrinone. In contrast, in urate-loaded rabbits that exhibit net tubular secretion of urate, intravenous DR-3438 (30 mg/kg) produced a significant decrease in FEua. Stop-flow studies in dogs revealed that DR-3438 (30 mg/kg) blocks both urate reabsorption and p-aminohippurate secretion in the proximal segment of the nephron and strongly inhibits reabsorption of water, sodium and potassium in the distal segments. These results suggest that DR-3438 exerts uricosuric activity through blocking urate transport in the proximal tubules and diuretic and saluretic activities by inhibiting water and sodium reabsorption in the distal segment of the nephron.

Animals↗
PubMed1989

Thromboxane A2 synthetase inhibitors. 2. Syntheses and activities of tetrahydronaphthalene and indan derivatives.

A series of 1-imidazolylalkyl-substituted or 5-thiazolylalkyl-substituted tetrahydronaphthalenecarboxylic acid and indancarboxylic acid derivatives were prepared and tested for the inhibitory activities of thromboxane A2 (TXA2) production in vitro and ex vivo. Most of the compounds showed potent TXA2 synthetase inhibitory activities in vitro and had long duration of inhibition of TXA2 production in rats when orally or intravenously administrated. The imidazole analogues had slightly less potency in vitro than the thiazole analogues, but the activities of the imidazole analogues in ex vivo models were equal or superior to the activities of the thiazole analogues. 6-(1-Imidazolyl-methyl)-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid hydrochloride hemihydrate (47a, DP-1904) was chosen for clinical studies.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Cyclic guanidines. 17. Novel (N-substituted amino)imidazo[2,1-b]quinazolin-2 ones: water-soluble platelet aggregation inhibitors.

A series of novel 1,2,3,5-tetrahydroimidazo[2,1-b]quinazolin-2-one derivatives substituted with a secondary amino group has been prepared and tested for the activities of inhibiting platelet aggregation in rats in vitro and ex vivo. Most of the compounds were found to be the potent inhibitors of platelet aggregation. Some of the active compounds were soluble in water and effective via iv infusion in rats. Structure-activity relationships have indicated that a lipophilic secondary amino group located at position 6 or 7 contributed to retention of potent activity. Among the compounds studied, 7-piperidino-1,2,3,5-tetrahydroimidazo[2,1-b]quinazolin-2- one (13 g,DN-9693) was the most favorable compound.

Animals↗
PubMed1984

Platelet-aggregating activities of metastasizing tumor cells. II. Variety of the aggregation mechanisms.

The mechanisms by which B16, 3LL and MH134 tumor cells induce platelet aggregation were studied. The B16 and 3LL tumors, which have high or moderate procoagulant activities, aggregated platelets only in the presence of Ca2+ and plasma factors. MH134, which had much lower procoagulant activity, aggregated platelets even in the absence of these factors. The induction of aggregation by B16 and 3LL could be prevented by thrombin inhibitors but not by the ADP scavenger, suggesting that thrombin, generated by procoagulant activities of tumor cells themselves, might play a major role in initiating aggregation. MH134-induced aggregation was not affected by any of the inhibitors, indicating that the mechanisms by which MH134 initiate platelet aggregation are independent of both thrombin and ADP.

Adenosine Diphosphate↗
PubMed1981

Cyclic guanidines. 14. Imidazo[1,2-a]thienopyrimidin-2-one derivatives as blood platelet aggregation inhibitors.

A series of novel 1,2,3,5-tetrahydroimidazo[1,2-a]thieno[2,3-d]-, -[3,2,-d]-, and -[3,4-d]pyrimidin-2-one derivatives has been prepared and tested for the activity of inhibiting platelet aggregation in rats in vitro and ex vivo. These compounds were synthesized through the following reactions: sodium borohydride reduction of 2,4-dichlorothienopyrimidines, followed by ethoxycarbonylmethylation and successive amination. Most of the compounds were found to be potent inhibitors of blood and platelet aggregation. Structure-activity relationships have indicated the essential contribution of the lactam structure and lipophilic substituents on the thiophene ring to the effective interaction of the compounds with a receptor site on the platelet. Among the compounds studied, 1,2,3,5,6,7,8,9-octahydro-[1]benzothieno[2,3-d]imidazo[1,2-a]pyrimidin-2-one (9m) exhibited the most favorable activity.

Animals↗