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排序方式: 共有254条查询结果,搜索用时 15 毫秒
221.
Yamagishi H Koike T Ohara S Horii T Kikuchi R Kobayashi S Abe Y Iijima K Imatani A Suzuki K Hishinuma T Goto J Shimosegawa T 《World journal of gastroenterology : WJG》2008,14(13):2049-2054
AIM: To compare rabeprazole (RPZ; 10 mg) with Lansoprazole orally disintegrating tablets (LPZ; 30 mg OD) in terms of antisecretory activity and blood drug concentration after a single dose. METHODS: Eight H pylori-negative cytochrome P450 (CYP) 2C19 extensive metabolizers were assigned to receive a single oral dose of RPZ 10 mg or LPZ 30 mg OD. Twelve hour intragastric pH monitoring was performed on the day of treatment. Blood samples were also collected after the administration of each drug. RESULTS: LPZ 30 mg OD induced a significantly earlier rise in blood drug concentration than RPZ 10 mg; consequently, LPZ 30 mg OD induced a significantly earlier rise in median pH in the third and fourth hours of the study. CONCLUSION: In H pylori-negative CYP2C19 extensive metabolizers, LPZ 30 mg OD induced a significantly faster inhibition of gastric acid secretion than RPZ 10 mg. 相似文献
222.
Kogushi M Matsuoka T Kawata T Kuramochi H Kawaguchi S Murakami K Hiyoshi H Suzuki S Kawahara T Kajiwara A Hishinuma I 《European journal of pharmacology》2011,657(1-3):131-137
Thrombin is a powerful agonist for platelets, the action of which is mediated by the thrombin receptor protease-activated receptor-1 (PAR-1). Recently, we discovered that E5555 (1-(3-tert-butyl-4-methoxy-5-morpholinophenyl)-2-(5,6-diethoxy-7-fluoro-1-imino-1,3-dihydro-2H-isoindol-2-yl) ethanone hydrobromide) is a potent thrombin receptor antagonist. We evaluated the anti-platelet and anti-thrombotic effects of E5555. E5555 inhibited the binding of a high-affinity thrombin receptor-activating peptide ([(3)H]haTRAP) to PAR-1 with a half maximal inhibitory concentration (IC(50)) value of 0.019μM. E5555 showed potent inhibitory effects on human platelet aggregation induced by thrombin and TRAP with IC(50) values of 0.064 and 0.031μM, respectively, but had no effect on platelet aggregation induced by either ADP or collagen. Similarly, E5555 showed potent and selective inhibitory effects on guinea pig platelet aggregation induced by thrombin and TRAP with IC(50) values of 0.13 and 0.097μM, respectively. The antithrombotic activity of E5555 in vivo was evaluated in a photochemically-induced thrombosis (PIT) model using guinea pigs. Oral administration of E5555 at 30 and 100mg/kg prolonged the time to occlusion by 1.8-fold and 2.4-fold, respectively, compared with controls. Furthermore, E5555 did not prolong bleeding time in guinea pigs at the highest tested dosage of 1000mg/kg. The drug interactions between E5555 and tissue plasminogen activator (tPA) were evaluated. Intravenous administration of 1mg/kg tPA significantly prolonged bleeding time, and its effects were not altered by the oral co-administration of 300mg/kg E5555. These results suggest that E5555 could be a therapeutic option for atherothrombotic disease. 相似文献
223.
Guerrero AP Hishinuma ES Andrade NN Nishimura ST Cunanan VL 《The International journal of social psychiatry》2006,52(4):343-359
BACKGROUND: Because of socioeconomic and acculturative challenges faced by immigrant families, Filipino adolescents in Hawai'i may be at risk for academic, behavioral and emotional difficulties. AIM: To determine, among Filipino adolescents in Hawai'i, whether measures of economic hardship and lower socioeconomic status (SES) correlate positively with poor school performance, aggressive behavior, substance use, anxiety, and depression; and whether family support and cultural identification correlate negatively with these difficulties. METHODS: 216 Filipino adolescents from four public high schools in Hawai'i (1993-1994) were given surveys that assessed basic demographic information, measures of family support and other social variables, and measures of school performance, depression, anxiety, aggression and substance use. RESULTS: In the total sample, low SES seemed to correlate with poor school performance and behavioral and emotional difficulties. In both the total sample and the sub-sample of adolescents with lower SES, family support was a universally strong protective factor. Learning genealogy was positively correlated with school performance, and speaking a language other than English was inversely correlated with substance use (in the whole sample) and depression (in the lower SES sub-sample). CONCLUSIONS: For Filipino adolescents (in both the whole and lower-SES samples), family support was an important protective factor against academic, behavioral and emotional difficulties. The role of cultural identification as a risk or protective factor among Filipino adolescents deserves further investigation. 相似文献
224.
225.
Mitsuo Mita Takuto Kuramoto Kazushi Ito Natsuko Toguchi‐Senrui Shigeru Hishinuma Michael P Walsh Masaru Shoji 《Clinical and experimental pharmacology & physiology》2010,37(3):350-357
1. In the present study, we compared the responsiveness of de‐endothelialized caudal artery smooth muscle strips, isolated from Type 2 diabetic Goto‐Kakizaki (GK) and normal Wistar rats, to α1‐adrenoceptor stimulation (cirazoline) and membrane depolarization (K+). 2. The contractile and myosin 20 kDa light chain (LC20) phosphorylation responses to 0.3 μmol/L cirazoline of caudal artery strips isolated from 12‐week‐old GK rats were significantly reduced compared with those of age‐matched Wistar rats, whereas the contractile and LC20 phosphorylation responses to 60 mmol/L K+ were unaltered. 3. Stimulation of fura 2‐AM‐loaded strips from GK rats with 0.3 μmol/L cirazoline induced a significantly smaller rise in [Ca2+]i (by ~20%) compared with that in strips from Wistar rats, whereas comparable Ca2+ transients were evoked by K+ in both. 4. Using quantitative polymerase chain reaction, no significant differences were detected in the mRNA expression of α1A‐, α1B‐ and α1D‐adrenoceptor subtypes between GK and Wistar rats. 5. Cirazoline (1 μmol/L)‐ and caffeine (20 mmol/L)‐induced contractions in the absence of extracellular Ca2+ were unaltered in GK rats, suggesting that the release of Ca2+ from the sarcoplasmic reticulum in response to cirazoline does not differ between GK and Wistar rats. 6. The results of the present study suggest that Ca2+ entry from the extracellular space via α1‐adrenoceptor‐activated, Ca2+‐permeable channels, but not via membrane depolarization and voltage‐gated L‐type Ca2+ channels, is impaired in caudal artery smooth muscle of GK rats. 相似文献
226.
Male and female BALB/c X DBA/2 F1 mice were treated with a diet containing 0.02% 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]-indole (Trp P-1), a hepatocarcinogenic tryptophan pyrolysate component, and the capacities of subcellular fractions of the liver to catalyze the mutagenic activation of Trp P-1 and its analogue Trp P-2 (4-demethylated Trp P-1) were examined by the in vitro Salmonella test with strain TA 98. In mice on control diet, both 9000 X g supernatant (S-9) and microsomal fractions from female mice livers displayed only 1.1- to 1.3-fold higher capacities for the mutagenic activation of either Trp P-1 or Trp P-2 than did those from male mice livers. When mice were treated with the Trp P-1 diet for 1 week, the S-9 activity in male mice for the Trp P-1 mutagenesis did not change, but that in females was increased to 2.5-fold of the female control. Treatment of mice with the dietary Trp P-1 for 2 weeks increased the S-9 activities to 2.8-fold in males and 4.9-fold in females of the same sex controls and the increased S-9 activities were not significantly changed by additional Trp P-1 feeding for 2 weeks. Similar changes in the S-9 activity were observed for the Trp P-2 mutagenesis. The overall changes in the S-9 activities induced by feeding Trp P-1 were reflected in the isolated microsomes. However, microsomes derived from the same volume of S-9 used exhibited only about one-half (Trp P-1) or one-third (Trp P-2) of the activity of the respective complete S-9 mixtures. Addition of liver cytosolic fractions (105,000 X g supernatants) from untreated or Trp P-1-treated mice to microsomes resulted in enhanced activities. Cytosols alone did not activate the compounds to mutagens. The microsome-mediated mutagenicity of either Trp P-1 or Trp P-2 was diminished by removal of NADPH from the assay system. It was also inhibited by addition of 7,8-benzoflavone and to a lesser extent by SKF 525A. Enzyme(s) for the mutagenic activation of Trp P-1 was induced by an i.p. injection of 3-methylcholanthrene to mice and to a lesser extent by an injection of phenobarbital, but no sex differences were observed in these enzyme inductions as opposed to the Trp P-1 feeding.(ABSTRACT TRUNCATED AT 400 WORDS) 相似文献
227.
Characteristics of the binding of [3H]-mepyramine to intact human U373 MG astrocytoma cells: evidence for histamine-induced H1-receptor internalisation. 下载免费PDF全文
1. The kinetics of the binding of 5 nM [3H]-mepyramine to sites on intact human U373 MG astrocytoma cells, sensitive to inhibition by 2 microM pirdonium, were temperature-dependent. At 37 degrees C the half-time for association was 0.9 +/- 0.4 min and at 4 degrees C 19 +/- 3 min. Dissociation of bound [3H]-mepyramine was fast at 37 degrees C, t0.5 1.5 +/- 0.3 min, but at 6 degrees C dissociation initiated by dilution or addition of unlabelled mepyramine was negligible over 120 min. The very slow dissociation at 6 degrees C made it possible to reduce the level of pirdonium-insensitive binding from 56 +/- 5% to 39 +/- 5% by washing the cells in ice-cold medium before filtration. 2. The binding of [3H]-mepyramine sensitive to 2 microM temelastine, measured after 10 min equilibration at 37 degrees C, failed to saturate and was resolved into an hyperbola and an apparently linear component, whereas the fit to the binding of [3H]-mepyramine sensitive to 2 microM pirdonium was not significantly improved over that to an hyperbola. The mean Kd for the binding of [3H]-mepyramine to the saturable component, 2.5 +/- 0.4 nM, was in close agreement with the value of 3.5 nM for mepyramine derived from inhibition of histamine H1-receptor-mediated inositol phosphate formation in U373 MG cells. 3. Curves for the inhibition of the binding of 5 nM [3H]-mepyramine to U373 MG cells by histamine H1-receptor antagonists were biphasic and were fitted to a two site-model. Affinities calculated from the best-fit IC50 values for the high-affinity site correlated well with those expected for binding to H1-receptors. 4. The percentages of the high-affinity site in curves of the inhibition of [3H]-mepyramine binding to intact U373 MG cells by two tertiary amine antagonists, norpirdonium and 4-methyldiphenhydramine, 68 +/- 3 and 63 +/- 4%, were significantly greater than the percentages of the high-affinity site in the inhibition curves of their quaternary derivatives, 50 +/- 1 and 45 +/- 3%, respectively. Similarly, the percentage of the high-affinity site for unlabelled mepyramine, 65 +/- 7%, was greater than for the non-cell penetrant H1-antagonist temelastine, 42 +/- 5%. 5. Incubation of U373 MG cells with 100 microM histamine at 37 degrees C, followed by washing twice in ice-cold medium and then incubation with 1-15 nM [3H]-mepyramine for 120 min at 4 degrees C, resulted in a decrease in the binding of [3H]-mepyramine sensitive to 2 microM pirdonium, compared to control cells not exposed to histamine. The binding of [3H]-mepyramine in the absence of pirdonium was not altered by histamine pretreatment, whereas the level of the pirdonium-insensitive binding was significantly increased, except after 1 min exposure to histamine. The decreases in the pirdonium-sensitive binding after 5, 10 and 60 min incubation with 100 microM histamine were 41 +/- 6, 56 +/- 6 and 67 +/- 8%, respectively, but the decrease after 1 min incubation with histamine, 16 +/- 8%, was not statistically significant. 6. The results are consistent with the binding of [3H]-mepyramine to intact U373 MG cells being to both plasma membrane and intracellular histamine H1-receptors. The high-affinity binding sensitive to the non-cell penetrant quaternary compounds and to temelastine is thus to plasma membrane H1-receptors. On exposure to 100 microM histamine receptors are translocated to the intracellular pool, since the change in the high-affinity binding of [3H]-mepyramine is primarily in the level of the pirdonium-insensitive binding, rather than in the total binding. 相似文献
228.
Iwao Ozawa Yoshiro Ogata Junichi Matsui Shoichi Hishinuma 《Journal of Hepato-Biliary-Pancreatic Surgery》1996,3(1):46-50
Hepatocellular carcinoma with tumor thrombus in the portal trunk and collateral veins in the hepatoduodenal ligament is usually considered to be unresectable. To resect the tumor, it is necessary to handle the portal trunk and bile duct after the hepatic artery and liver parenchyma have been transected without dissection of the hepatoduodenal ligament. In this way, we were able to perform right lobectomy with removal of the tumor thrombus in the portal trunk, avoiding profuse bleeding due to transection of the collateral veins. Our procedure is associated with certain problems, one being whether the tumor thrombus can be separated from the endothelium of the portal vein, and another being related to the radical extent of this operation. The major issue is the radical nature of this procedure. It is presumed that the collateral veins can be extirpated to achieve a curative operation. 相似文献
229.
H Shimizu Y Koyama I Ozawa T Inada S Hishinuma K Kotake T Ikeda Y Ogata M Hagiwara K Suzuki 《Gan no rinsho》1990,36(11):2047-2052
Reported is the case of an esophageal cancer presenting a renal metastasis, which was detected and resected as the only recurrent focus. The patient was a 62-year-old male. Five months after an esophagectomy, a left renal mass was detected by abdominal computerized tomography, and a rise in the SCC antigen. The urinary cytology suggested a renal metastasis of the esophageal cancer. Thus, chemotherapy and irradiation was performed, followed by a resection. The histology of the resected mass showed a squamous cell carcinoma, similar to the findings at the primary site. A renal metastasis of an esophageal carcinoma usually is latent, but not rarely found on postmortem examination. A nephrectomy for a renal metastasis of an esophageal cancer is rare, and only 8 cases are reported in the literature. 相似文献
230.
H Sato F Ishizawa H Hirayama T Hishinuma M Mizugaki 《Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan》1992,112(3):199-202
Quenching effects of anthraquinones on the extra-weak chemiluminescence (CL) derived from lipid peroxidation in rat brain homogenates were investigated. Such anthraquinone derivatives as emodin, rhein, and alizarin quenched the CL, while anthraquinone did not quench the CL. A linear relationship between CL-quenching activity and inhibitory rate of malondialdehyde production of various compounds was demonstrated. This technique is useful for the screening method of antioxidants. 相似文献