巻号一覧
51 巻 (1989)
- 4 号 p. 455-
- 3 号 p. 309-
- 2 号 p. 151-
- 1 号 p. 1-
51 巻, 4 号
選択された号の論文の18件中1～18を表示しています
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Syozo MATSUOKA, Mayumi FUTAGAMI, Hiroyuki OHNO, Katsuhiro IMAKI, Tadao ...1989 年 51 巻 4 号 p. 455-463
発行日: 1989年
公開日: 2006/08/25
ジャーナル フリーThe effect of ONO-3307 (4-sulfamoyl phenyl-4-guanidinobenzoate methanesulfonate), a new protease inhibitor, was studied on various proteases in vitro and in an experimental thrombosis model in vivo. ONO-3307 competitively inhibited trypsin, thrombin, plasma kallikrein, plasmin, pancreatic kallikrein and chymotrypsin; and their Ki values were 0.048 μM, 0.18 μM, 0.29 μM, 0.31 μM, 3.6 μM and 47 μM, respectively. In addition, ONO-3307 inhibited both elastase release from N-formyl-Met-I-eu-Phe (fMLP) -stimulated leukocytes and tissue thromboplastin release from endotoxin-stimulated leukocytes. To examine the effects of ONO-3307 on disseminated intravascular coagulation (DIC), we developed an experimental thrombosis model. ONO-3307 (10 mg/kg/hr) completely inhibited the deposition of radioactive fibrin in kidney and lung. Gabexate mesilate (50 mg, /kg/hr) was also effective in this model, but the effect of nafamostat mesilate was unclear. These results indicate that ONO-3307 exhibits a wide range of inhibitory effects on various proteases, and ONO-3307 may be useful for the treatment of protease-mediated diseases such as thrombosis and DIC.抄録全体を表示PDF形式でダウンロード (457K) -
Ryoji KOJIMA, Mikio ITO, Yoshio SUZUKI1989 年 51 巻 4 号 p. 465-473
発行日: 1989年
公開日: 2006/08/25
ジャーナル フリーWe investigated the effect of latamoxef (LMOX) on the binding of tobramycin JOB) to brush border membranes (BBMs) isolated from rat kidney cortex by calcium precipitation. The simultaneous treatment with TOB (0.2 mM) and LMOX (10 and 20 mM) to the BBMs fraction (about 250 μg protein) significantly inhibited the binding of TOB to BBMs. The addition of the reaction mixture of TOB (0.2 mM) and LMOX (4, 10 and 20 mM) which was preincubated for 3 hr at 37°C, to the BBMs fraction resulted in less binding of TOB to the membranes than that observed in the case of simultaneous treatment with both drugs. Although [14C]-labeled LMOX was taken up by BBMs temperature and timedependently, the pretreatment with LMOX showed no obvious differences in inhibition of the TOB binding to BBMs, as compared with the result from simultaneous treatment with both drugs. Additionally, the binding of TOB to the LMOXtreated BBMs that were resuspended in fresh medium after the pretreatment with LMOX for 10 min at 37°C was similar to that of TOB to the non-treated BBMs. These results indicate that LMOX inhibits the binding of TOB to BBMs not by binding to BBMs but by interacting with TOB.抄録全体を表示PDF形式でダウンロード (506K) -
Keitaro HASHIMOTO, Kozo WATANABE, Seiichiro MOCHIZUKI, Akira TOMIYAMA1989 年 51 巻 4 号 p. 475-482
発行日: 1989年
公開日: 2006/08/25
ジャーナル フリーAntiarrhythmic effects of the new drug KT-362, which was reported to suppress Na and Ca currents of cardiac cells and also to suppress intracellular Ca release in isolated smooth muscle preparations, were examined using two-stage coronary ligation-, digitalis and adrenaline-induced ventricular arrhythmias in the dog. Intravenous KT-362 at 10 mg/kg suppressed coronary ligation arrhythmia both at 24 and 48 hr after ligation, and the minimum effective plasma concentrations for arrhythmias induced by 24 hr coronary ligation and 48 hr coronary ligation were 6.1±1.7 and 8.6±2.7 μg/ml, respectively. Antiarrhythmic effects were accompanied by transient hypotension. Oral administration of 70-100 mg/kg was also effective on 24 hr coronary ligation arrhythmia. However, there was no prominent hypotension in these experiments. Intravenous KT-362 at 3 mg/kg suppressed digitalis arrhythmia; and the minimum effective plasma concentration was 3.3±1.2 μg/ml, which was lower than the effective plasma concentrations for coronary ligation arrhythmias. Intravenous KT-362 at 1 mg/kg also suppressed adrenaline arrhythmia; and the minimum effective plasma concentration was 1.0±0.1 μg/ml, the lowest among the effective plasma concentrations. These pharmacological profiles of KT362 are quite different from those of class 4 Ca antagonists, but similar to those of class 1 drugs such as propafenone. Though KT-362 has a hypotensive effect, it is effective on canine ventricular arrhythmias; thus its clinical usefulness for supraventricular and ventricular arrhythmias is expected.抄録全体を表示PDF形式でダウンロード (435K) -
Hironori TANAKA, Koji TAKEUCHI, Susumu OKABE1989 年 51 巻 4 号 p. 483-492
発行日: 1989年
公開日: 2006/08/25
ジャーナル フリーSubcutaneous administration of mepirizole (60 and 200 mg/kg) and cysteamine (100 and 300 mg/kg) to fasted rats consistently induced localized villous damage to the proximal duodenum after 6 to 8 hr. The severity of the damage in animals treated with the low doses remained unchanged at 12 hr. With the high doses, however, well-defined deep ulcers were evident by that time, the incidence being high. The agents caused a significant accumulation of highly acidic gastric contents for 6 to 8 hr, but the accumulated gastric contents had markedly decreased by 12 hr. The intraduodenal pH in these animals was significantly lowered for 8 hr with the low doses, but for 12 hr with the high doses. Both mepirizole and cysteamine significantly delayed gastric emptying which was quantitated by weighing the food residue in refed animals. This delay in emptying was observed for 6 to 8 hr with the low doses and for 12 hr with the high doses. We conclude that this prolonged accumulation of gastric contents for up to 8 hr, resulting in a continuous lowering of the intraduodenal DH for 12 hr, is a crucial factor for the progression from duodenal villous damage to visible ulcers in response to mepirizole and cysteamine.抄録全体を表示PDF形式でダウンロード (534K) -
Junichi KURIHARA, Tatsuhiro SAHARA, Hitoshi KATO1989 年 51 巻 4 号 p. 493-499
発行日: 1989年
公開日: 2006/08/25
ジャーナル フリーIn a canine model of transient global cerebral ischemia, the correlation between the decrease in baroreflex sensitivity (BRS) following 5-min ischemia and the degree of ischemia or post-ischemic hypoperfusion was investigated. Although the medulla oblongata and the cerebral cortex suffered a similar degree of ischemia, the extent of post-ischemic decrease in BRS was inversely correlated with the residual blood flow during ischemia in the medulla, but not with that in the cerebral cortex. A similar degree of post-ischemic hypoperfusion occurred in the medulla and the cerebral cortex. However, the extent of decrease in BRS was not correlated with the degree of hypoperfusion, and the cortical EEG was not significantly affected. These results suggest that the decrease in BRS may be due to the functional damage in the medulla and that the selective decrease in BRS without concomitant impairment of the EEG cannot be ascribed to the regional difference in the degree of ischemia or post-ischemic hypoperfusion.抄録全体を表示PDF形式でダウンロード (356K) -
Kiyoshi OIZUMI, Hiroshi NISHINO, Masaaki MIYAMOTO, Junichiro FUKUSHIGE ...1989 年 51 巻 4 号 p. 501-508
発行日: 1989年
公開日: 2006/08/25
ジャーナル フリーCS-905 is a potent dihydropyridine calcium blocker that has a gradual and long-lasting antihypertensive action with little tachycardia in SHR. In this study, we investigated chronic and acute effects of CS-905 on renal functions in SHR. To examine the chronic effects, 23 week-old male SHR were treated with CS-905 (1 or 3 mg/kg/day, p.o.) or 0.3% CMC (carboxymethylcellulose). After the 15 weektreatment, the agent dose-relatedly lowered systolic blood pressure measured 24 hr after the final administration (184±2 and 173±3 mmHg at 1 and 3 mg/kg/day vs. 218±4 mmHg for the control group). Natriuresis and the reduction of urinary protein excretion were also observed in the CS-905 treated groups. Urinary NAG (N-acetyl-β-D-glucosaminidase) activity tended to decrease, but not significantly. Histopathological changes observed in the SHR kidney were reduced by chronic treatment with CS-905. On a single oral administration in 38 week-old SHR, CS-905 caused natriuresis at a dose of 3 mg/kg, but did not affect urinary protein excretion and urinary NAG activity. These effects of CS-905 on renal functions may be beneficial in the treatment of hypertension.抄録全体を表示PDF形式でダウンロード (544K) -
Hironori TANAKA, Koji TAKEUCHI, Susumu OKABE, Motonobu MURAKAMI1989 年 51 巻 4 号 p. 509-519
発行日: 1989年
公開日: 2006/08/25
ジャーナル フリーMepirizole (200 mg/kg) and cysteamine (100 mg/kg) induced epithelial cell damage in the proximal duodenum of rats within 30 min after s.c. administration. The injury induced was severe 60 min later. Gastric acid secretion determined in intact animals was stimulated by these agents 30 and 60 min later when the intraluminal pH of the duodenum was significantly decreased. Duodenal blood flow was significantly decreased beginning 5 min after administration up to 60 min. Oral treatment with sodium bicarbonate (300 mg/kg), cimetidine (100 mg/kg), omeprazole or NC-1300 (gastric proton pump inhibitors, 30 mg/kg) and 16, 16-dimethyl prostaglandin E2 (10μg/kg) protected the epithelium from damage induced by the two duodenal ulcerogens. Epithelial cell damage in the duodenum in response to mepirizole and cysteamine appears to be related to the increased gastric acid secretion followed by lowered intraduodenal pH of the duodenum having decreased blood flow.抄録全体を表示PDF形式でダウンロード (589K) -
Tadashi NAGAMATSU, Junko KOJIMA, Mikio ITO, Nobuyuki KONDO, Yoshio SUZ ...1989 年 51 巻 4 号 p. 521-530
発行日: 1989年
公開日: 2006/08/25
ジャーナル フリーThe antinephritic effects of PGE1, TEI-5178 and TEI-6122 on crescentictype anti-glomerular basement membrane (GBM) nephritis in rats were investigated. The test compounds were subcutaneously administered every day for 39 days after the injection of anti-GBM serum. PGE1 (2.0 mg/kg/day), TEI-5178 (0.25 or 0.5 mg/ kg/day) and TEI-61 22 (0.25 or 0.5 mg/kg/day) significantly reduced urinary protein by 30 to 50% of that of the control at the late stage of nephritis. These test compounds also suppressed the increase of blood urea nitrogen and the development of alteration in the glomeruli by the 40th day. Both TEI-5178 (0.5 mg/kg/day) and TEI-6122 (0.5 mg/kg/day) significantly suppressed the production of antibody to rabbit γ-globulin in nephritic rats. This was not the case with PGE1, however. In additional experiments to clarify the antinephritic mechanisms of the test compounds, it was found that 15 min after one subcutaneous injection of PGE1, (1.0 mg/kg), TEI-5178 (0.5 mg/kg) or TEI-6122 (0.5 mg/kg), systolic blood pressure in the nephritic rats was transiently reduced by 50 to 60%. On the other hand, these test compounds augmented renal blood flow (20-50%) from 45 min after the injection. The relationship between the antinephritic effect and these subsequent findings will be discussed.抄録全体を表示PDF形式でダウンロード (499K) -
Katsuaki ITO, Takaaki IKEMOTO, Shitomi AOKI, Mikio OTA1989 年 51 巻 4 号 p. 531-538
発行日: 1989年
公開日: 2006/08/25
ジャーナル フリーWe compared the effects of ryanodine and 9, 21 -didehydroryanodine (DH-ryanodine), which are present in commercial preparations of ‘ryanodine’, on the contractions of rat and guinea pig aortae induced by 20 mM caffeine and tested the dependence of the action of each substance on external Ca2+. With the first protocol, the aortae were incubated with ryanodine or DH-ryanodine for 20 min in Ca2+-containing medium, and caffeine was added at 2 min incubation in Ca2+-free medium. With the second protocol, each substance was added when the external medium was changed to Ca2+-free medium, and 20 min later, caffeine was applied. Ryanodine and DH-ryanodine inhibited the caffeine-induced contractions in a similar way; i.e., with maximal effects at 3 μM and lesser effects at 10μM. The potencies of inhibition by both substances were similar except that the effect of ryanodine at 1.5μM was more potent than that of DH-ryanodine with the second protocol. The response by muscles previously loaded with Ca2+ to a second application of caffeine was more greatly inhibited by both compounds (use-dependent effect). The inhibition of the contraction due to the first or second application of caffeine was greater when either agent was applied in Ca2+-containing medium than in Ca2+-free medium. These results indicate that ryanodine and DH-ryanodine are similar in their effects on caffeine-induced Ca2+ release in vascular smooth muscle and that cellular Ca2+ levels may affect the action of ryanodine.抄録全体を表示PDF形式でダウンロード (445K) -
Noboru NAKAHARA, Yoshinori IGA, Yasunari SAITO, Fumio MIZOBE, Gosei KA ...1989 年 51 巻 4 号 p. 539-547
発行日: 1989年
公開日: 2006/08/25
ジャーナル フリーThe effects of FKS-508 [AF102B; cis 2-methylspiro(1, 3-oxathiolane5, 3')quinuclidine], a selective M1 muscarinic receptor agonist, were examined to predict the possible activity on memory disorders using a T-maze and radial-arm maze task in experimental amnesia models. The amnesia models were produced by bilateral intracerebroventricular injection of ethylcholine aziridinium ion (AF64A), a selective cholinotoxin, in rats. Repeated administrations of FKS-508 (5 mg/kg/day, i.p.) for 5 weeks significantly ameliorated impaired performance of AF64A-treated rats (AF64A-rats) in a delayed alternation task in the T-maze. Repeated administrations of FKS-508 (1 and 5 mg/kg/day, p.o.) for 5 weeks significantly ameliorated acquisition failures of AF64A.-rats in a radial-arm maze task. Single administration of FKS-508 (1 and 5 mg/kg, p.o.) significantly reduced the incorrect choices of AF64A-rats in a radial-arm maze task with 6 hr-delay time. No abnormalities in general behaviors, such as loss of appetite and ataxia, were observed in rats treated with FKS-508 repeatedly during 5 weeks. Our present results showed that FKS508 can ameliorate memory impairments in AF64A-rats with central cholinergic hypofunction without causing any behavioral abnormalities. FKS-508 may be considered as a candidate for the clinical examination of the cholinergic hypothesis of senile dementia of the Alzheimer type.抄録全体を表示PDF形式でダウンロード (549K) -
Masami FUJIWARA, Kensuke SHIBATA, Noriyasu TAKAYANAGI, Kenji MATSUNARI ...1989 年 51 巻 4 号 p. 549-554
発行日: 1989年
公開日: 2006/08/25
ジャーナル フリーThe in vitro and in vivo effects of the newly synthesized compound TOK-8801 (N-(2-phenylethyl)-3, 6, 6-trimethyl-5, 6-dihydroimidazo[2, 1-b]thiazole2-carboxamide) on immune responses were investigated in comparison with that of levamisole (LMS). TOK-8801 enhanced the anti-sheep red blood cells (SRBC) plaque forming cells (PFC) response and mitogen-induced proliferative responses in murine splenocytes and thymocytes in vitro at concentrations of 10-7-10-5 M, while LMS augmented these responses at 10-4M. The stimulatory effect of TOK-8801 as well as LMS on the antibody production was eliminated by the removal of T cells. TOK-8801 (0.5 mg/kg, p.o.) suppressed the in vivo generation of anti-SRBC PFC in normal mice, but the compound restored the depressed antibody production in restraint-stress mice which was mainly caused by helper T cell defects. From these results, TOK-8801 was shown to have an immunomodulatory activity in the antibody production.抄録全体を表示PDF形式でダウンロード (320K) -
Mitsuyoshi NINOMIYA, Tomoko TANI, Motohiko UEDA1989 年 51 巻 4 号 p. 555-562
発行日: 1989年
公開日: 2006/08/25
ジャーナル フリーIn the His bundle and ventricular electrograms of Langendorff-perfused guinea pig hearts driven at a cycle length of 450 or 700 msec, S-1389 (711 389-S), a new antiarrhythmic agent, above 3×10-7 or 10-6 M increased the basal conduction times in the following order: His-Purkinje system >ventricular and atrial muscles > atrioventricular (AV) node. Slowing of the ventricular and AV nodal conduction of extrasystoles with variable coupling intervals was also caused by 5-1389. S-1389 above 10-6 or 3×10-6 M significantly prolonged the functional and/or effective refractory periods of the AV node and ventricle. Disopyramide (3×10-6-3×10-5M) also produced similar effects, but they were much less potent than those of S-1389. Although disopyramide did not produce the rate-dependent increases in the atrial and AV nodal conduction times and in the AV nodal refractory period, S-1389 increased these parameters rate-dependently.抄録全体を表示PDF形式でダウンロード (469K) -
Kenji HIRATE, Hisashi KURIBARA, Sakutaro TADOKORO1989 年 51 巻 4 号 p. 563-567
発行日: 1989年
公開日: 2006/08/25
ジャーナル フリーCharacteristics of acquisition and retention of the one-training and repeated-training passive avoidance responses of the step-through type were investigated in 3 lines of so-called Wistar strain rats: HLA:Wistar, JLA:Wistar and Std: Wistar and in F344/Du Crj rats. In the adaptation and the first acquisition trials in the repeated-training task, Std:Wistar rats took comparatively longer latency times to enter the dark chamber from an illuminated runway than the other lines and strain of rats. In contrast, JLA:Wistar rats took a number of trials to stay for 300 sec or longer in the runway. HLA:Wistar, Std:Wistar and F344/Du Crj rats showed similar response !atencies in the first retention trial. J LA:Wistar rats showed the shortest latencies among 3 lines of Wistar and F334/Du Crj rats, exhibiting much poorer acquisition and retention abilities than the other rats. The response latencies in the retention trials were longer in the order of HLA:Wistar =≥ F344/Du Cri > Std:Wistar > JAL:Wistat rats. These results suggest that there are marked breeder differences in their passive avoidance response even in the rats that have the same strain name.抄録全体を表示PDF形式でダウンロード (300K) -
Motonobu MURAKAMI, Jung Keun YOO, Sanae TERAMURA, Ko YAMAMOTO, Hiroshi ...1989 年 51 巻 4 号 p. 569-571
発行日: 1989年
公開日: 2006/08/25
ジャーナル フリーWe examined the role of gastric ammonia in the development of gastric lesions in rats. Exposure of the gastric mucosa to ammonia (30 mM) produced microscopic injury, but no macroscopic lesion was observed. However, exposure of the stomach to ammonia in rats subjected to ischemia resulted in macroscopic gastric lesions. The macroscopic lesions were markedly inhibited by pretreatment with taurine, a scavenger of hypochlorous acid (HOCI) and monochloramine (NH2CI). These results indicate that ammonia is deleterious to gastric mucosa, and monochloramine may be involved in the pathogenesis of ammonia-induced mucosal lesions.抄録全体を表示PDF形式でダウンロード (152K) -
Yoshio NAKAJIMA, Naomi WADA1989 年 51 巻 4 号 p. 572-576
発行日: 1989年
公開日: 2006/08/25
ジャーナル フリーThe effect of eperisone-HCI on the spinal stretch reflex was investigated in cats anesthetized with urethane-chloralose. The reflex activity, elicited by muscle stretches, was recorded from the split ventral root and analyzed using a crosscorrelation histogram between the motoneuronal spikes and muscle stretches. Eperisone-HCI was intravenously applied at a dose of 5 mg/kg. It was found that eperisone weakly inhibited the reflex activity of tonic motoneurons (approximately 30%), and that of the phasic ones was either moderately (approximately 70%) or completely (100%) inhibited by eperisone. The cross-correlation analysis suggested that the membrane potentials of both tonic and phasic motoneurons are equally lowered by eperisone or that monosyn.p tic transmission from primary afferents of muscle spindles to motoneurons is inhibited by eperisone.抄録全体を表示PDF形式でダウンロード (267K) -
Shigeki MIYAKE, Hiroshi SHIGA, Toshio SADA, Kiyoshi OIZUMI, Hiroyuki K ...1989 年 51 巻 4 号 p. 577-580
発行日: 1989年
公開日: 2006/08/25
ジャーナル フリーAfter the use of two radionuclides in the tracer microspheres technique in the rat was verified, we examined the central and peripheral hemodynamic effects of RS-1893, an orally active cardiotonic agent. An intravenous infusion of RS-1893 at a dose of 3 μg/kg/min gradually decreased blood pressure and increased heart rate and cardiac output. Blood flows in the kidney and stomach were increased. There was no organ in which blood flow was decreased despite the fall in blood pressure. These data suggest that RS-1893 dilates blood vessels in the whole body, especially in the kidney and stomach.抄録全体を表示PDF形式でダウンロード (233K) -
Yoshinori ITOH, Ryozo OISHI, Masahiro NISHIBORI, Kiyomi SAEKI1989 年 51 巻 4 号 p. 581-584
発行日: 1989年
公開日: 2006/08/25
ジャーナル フリーThe turnover rates, rate constants and half-life values of neuronal histamine (HA) in 10 nuclei of the rat hypothalamus were estimated from the depletion of HA induced by α-fluoromethylhistidine (α-FMH: 100 mg/kg, i.p.), a specific inhibitor of histidine decarboxylase, on the presumption that α-FMH depletable HA pools represent neuronal ones. Marked variation in the HA turnover rates were observed among the hypothalamic nuclei, ranging from 5.7 to 19.5 pmole/mg protein/hr.抄録全体を表示PDF形式でダウンロード (223K) -
Kiyoshi NAGATA, Masaaki MIYATA, Miki SHIMADA, Yasushi YAMAZOE, Ryuichi ...1989 年 51 巻 4 号 p. 585-588
発行日: 1989年
公開日: 2006/08/25
ジャーナル フリーHepatic level of mRNA for P-450g was determined in male and female rats of Sprague-Dawley, ACI and Fischer strains using a specific oligonucleotide probe. The mRNA level in female Sprague-Dawley and Fischer rats was undetectable in accordance with a very low or undetectable level of P-450g protein. The mRNA was detected in all male ACI rats, in which high levels of P-450g protein were detected. In Fischer male rats, mRNA for P-450g was clearly detected in the liver, but P-450g protein was not detected. Moreover, the mRNA was detected in the liver of all male Sprague-Dawley rats, irrespective of the expressed level or absence of P-450g protein. As a most plausible explanation of the observed discordance in the levels of P-450g mRNA and protein, translation of unstable protein for microheterogenous P-450g is discussed.抄録全体を表示PDF形式でダウンロード (213K)
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