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21.
Protective effects of SEA0400, a novel and selective inhibitor of the Na+/Ca2+ exchanger,on myocardial ischemia-reperfusion injuries 总被引:8,自引:0,他引:8
Takahashi K Takahashi T Suzuki T Onishi M Tanaka Y Hamano-Takahashi A Ota T Kameo K Matsuda T Baba A 《European journal of pharmacology》2003,458(1-2):155-162
The Na(+)/Ca(2+) exchanger (NCX) is involved in myocardial ischemia-reperfusion injuries. We examined the effects of 2-[4-[(2,5-difluorophenyl)methoxy]phenoxy]-5-ethoxyaniline (SEA0400), a potent and selective inhibitor of NCX, on myocardial ischemia-reperfusion injury models. In canine cardiac sarcolemmal vesicles and rat cardiomyocytes, SEA0400 potently inhibited the Na(+)-dependent 45Ca(2+) uptake with an IC(50) value of 90 and 92 nM, compared with 2-[2-[4-(4-nitrobenzyloxy)phenyl]isothiourea (KB-R7943, 7.0 and 9.5 microM), respectively. In rat cardiomyocytes, SEA0400 (1 and 3 microM) attenuated the Ca(2+) paradox-induced cell death. In isolated rat Langendorff hearts, SEA0400 (0.3 and 1 microM) improved the cardiac dysfunction induced by low-pressure perfusion followed by normal perfusion. In anesthetized rats, SEA0400 (0.3 and 1 mg/kg, i.v.) reduced the incidence of ventricular fibrillation and mortality induced by occlusion of the left anterior descending coronary artery followed by reperfusion. These results suggest that SEA0400 is a most potent NCX inhibitor in the heart and that it has protective effects against myocardial ischemia-reperfusion injuries. 相似文献
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23.
Ryohei Hasegawa Fumio Furukawa Kazuhiro Toyoda Hidetaka Sato Michihito Takahashi Yuzo Hayashi 《Cancer science》1990,81(5):483-488
Intravesical instillation of 2-phenyl-1,4-benzoquinone (PBQ), a metabolite of sodium o -phenylphenate (Na-OPP), at a concentration of 0.1% in saline caused acute epithelial injury, prolonged inflammation and epithelial hyperplasia in female F344 rats. Ten such instillations of PBQ within 5 weeks resulted in the development of preneoplastic lesions of the urinary bladder epithelium when followed by 5% sodium saccharin feeding for 31 weeks. Since neither urothelial damage nor tumor-initiating activity was observed with either Na-OPP itself or another metabolite, phenylhydroquinone, PBQ may play an essential role in Na-OPP urinary bladder carcinogenesis. 相似文献
24.
Hideya Niimura Akira Matsunaga Koichiro Kumagai Kazuo Ohwaki Masahiro Ogawa Hiroo Noguchi Kazue Yonemura Keijiro Saku 《Circulation journal》2004,68(8):740-746
BACKGROUND: Brugada syndrome is a form of idiopathic ventricular fibrillation characterized by right bundle-branch block pattern and ST elevation in the right precordial leads of the ECG. The SCN5A gene encodes the alpha-subunit of the human heart sodium channel, which plays a critical role in cardiac excitability, and mutations of SCN5A could underlie Brugada syndrome. METHODS AND RESULTS: To detect mutations of SCN5A, DNA samples from 12 Japanese patients with Brugada syndrome were analyzed using direct sequencing. Two patients had novel mutations, G292S and S835L, but no other mutations of SCN5A were detected in the remaining patients. The first mutation, G292S, was identified adjacent to the pore-lining region between the DIS5 and DIS6 transmembrane segments of SCN5A, and the second mutation, S835L, was in the intracellular loop connecting the DIIS4 to DIIS5. Both mutations were not detected in 100 unrelated control subjects. CONCLUSION: Two novel SCN5A mutations have been found in Japanese patients with Brugada syndrome. 相似文献
25.
26.
Toshikazu Ushijima Masahiro Tsutsumi Ryuichi Sakai Yukihito Ishizaka Fumimaro Takaku Yoichi Konishi Michihito Takahashi Takashi Sugimura Minako Nagao 《Cancer science》1991,82(9):965-968
Five pancreatic carcinomas induced by N -nitrosobis(2-hydroxypropyl)amine in Syrian golden hamsters were analyzed for activation of Ki- ras at codons 12 and 13, using the polymerase chain reaction and direct sequencing. The Ki- ras gene was shown to be activated in four of the five carcinomas, and the results were further confirmed by subcloning and sequencing. All the mutations involved a G-to-A transition at the second position of codon 12, which resulted in a change at the amino acid level from glycine to aspartic acid. This mutation is identical with that reported for pancreatic tumors of Syrian hamsters induced by N -nitrosobis(2-oxopropyl)amine. 相似文献
27.
28.
Multiple forms of immunoreactive renin in human adrenocortical tumour tissue from patients with primary aldosteronism 总被引:1,自引:0,他引:1
K Mizuno M Ojima S Hashimoto M Tani S Niimura N Kunii R Yabe H Watari T Inagami S Fukuchi 《Clinical science (London, England : 1979)》1987,72(6):699-704
There is increasing evidence which suggests that the adrenal gland contains the renin-angiotensin cycle. The localization of renin has been reported to be mainly in the zona glomerulosa rather than the fasciculata medullary portion. In the present study we have investigated extracts from aldosteronomas (n = 3), which are believed to derive from the zona glomerulosa cells. In addition, we have attempted to characterize the biochemical properties of the adrenal renin. Sizable quantities of renin-like activity (32.0 +/- 7.7 ng of angiotensin I generated h-1 mg-1 of protein, mean +/- SEM) were detected in the extracts. This renin-like activity was inhibited by anti-renin antibody raised against pure renin (mean, 95% of the total renin-like activity), indicating that it was not due to the non-specific action of proteases such as cathepsin D. The optimum pH of the tissue renin-like enzyme was 6.0 for rat plasma substrate. Differences were found, however, in the molecular mass (36,000, 37,000, 44,000 and 48,000), binding to concanavalin A and isoelectric points (4.40, 4.68 and 5.00). These results confirm the existence of specific renin in aldosteronoma. Renin microheterogeneity could be evidence for local production of the enzyme. 相似文献
29.
Ichino N Osakabe K Nishikawa T Sugiyama H Kato M Kitahara S Hashimoto S Kawabe N Harata M Nitta Y Murao M Nakano T Arima Y Shimazaki H Suzuki K Yoshioka K 《World journal of gastroenterology : WJG》2010,16(38):4809-4816
AIM:To construct and evaluate a new non-invasive fibrosis index for assessment of the stage of liver f ibrosis. METHODS:A new f ibrosis index (Fibro-Stiffness index) was developed in 165 of 285 patients with chronic hepatitis C, and was validated in the other 120 patients where liver biopsy was performed. Its usefulness was compared with liver stiffness (LS) measured by FibroScan, the aminotransferase-to-platelet ratio index, the Forns index and the FibroIndex. RESULTS: The Fibro-Stiffness index consists of... 相似文献
30.
Yukiko Aono Yuji Yamazaki Junichi Yasutake Takehisa Kawata Hisashi Hasegawa Itaru Urakawa Toshiro Fujita Michihito Wada Takeyoshi Yamashita Seiji Fukumoto Takashi Shimada 《Journal of bone and mineral research》2009,24(11):1879-1888
X‐linked hypophosphatemia (XLH), characterized by renal phosphate wasting, is the most common cause of vitamin D‐resistant rickets. It has been postulated that some phosphaturic factor plays a causative role in XLH and its murine homolog, the Hyp mouse. Fibroblast growth factor 23 (FGF23) is a physiological phosphaturic factor; its circulatory level is known to be high in most patients with XLH and Hyp mice, suggesting its pathophysiological role in this disease. To test this hypothesis, we treated Hyp mice with anti‐FGF23 antibodies to inhibit endogenous FGF23 action. A single injection of the antibodies corrected the hypophosphatemia and inappropriately normal serum 1,25‐dihydroxyvitamin D. These effects were accompanied by increased expressions of type IIa sodium‐phosphate cotransporter and 25‐hydroxyvitamin‐D‐1α‐hydroxylase and a suppressed expression of 24‐hydroxylase in the kidney. Repeated injections during the growth period ameliorated the rachitic bone phenotypes typically observed in Hyp mice, such as impaired longitudinal elongation, defective mineralization, and abnormal cartilage development. Thus, these results indicate that excess actions of FGF23 underlie hypophosphatemic rickets in Hyp mice and suggest a novel therapeutic potential of the FGF23 antibodies for XLH. 相似文献