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91.
The in vitro and in vivo effects of 3-formylamino-7-methylsulfonylamino-6-phenoxy-4H-1-benzopyran-4-on e (T-614, CAS 123663-49-0), a new antiinflammatory agent, on arachidonic acid metabolism were investigated in comparison with those of reference drugs. Although the inhibitory effect of T-614 on the synthesis of prostaglandins by rabbit renal microsomes was very weak (IC50 of 58 micrograms/ml), T-614 effectively inhibited the prostaglandin E2 (PGE2) generation by mouse fibroblasts stimulated with bradykinin with an IC50 value of 0.47 micrograms/ml. The suppressive effect of T-614 on the PGE2 generation in fibroblasts was also found when cells were stimulated with Ca ionophore A23187, but not when induced with arachidonic acid. T-614 suppressed the A23187-induced PGE2 generation by rat macrophages, but not the leukotriene B4 production. In addition, 5-lipoxygenase activities in guinea-pig peritoneal exudated cells were not inhibited. In in vivo experiments, at doses of more than 1 mg/kg, T-614 reduced the PGE2 contents in inflammatory exudate of rat carrageenin-sponge type inflammation, but it was almost inactive in inhibiting gastric prostaglandins production up to 100 mg/kg. T-614 also did not affect the urinary PGE2 excretion in rats, and slightly inhibited the thromboxane synthesis in rat blood. Furthermore, the convulsion-induced increase of PGE2 in mouse brain was inhibited by T-614. These data suggest that T-614 inhibits the production of cyclooxgenase-mediated products with apparently different mode from classical non-steroidal antiinflammatory drugs, and may partly explain the discrepancy in pharmacological properties between this compound and other drugs. 相似文献
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Kazuhiko Sonoyama Haruaki Ninomiya Osamu Igawa Yasuhiro Kaetsu Yoshiyuki Furuse Toshihiro Hamada Junichiro Miake Peili Li Yasutaka Yamamoto Kazuhide Ogino Akio Yoshida Shin-ichi Taniguchi Yasutaka Kurata Satoshi Matsuoka Toshio Narahashi Goshi Shiota Yoshihisa Nozawa Hiroaki Matsubara Masatsugu Horiuchi Yasuaki Shirayoshi Ichiro Hisatome 《Hypertension research》2006,29(11):923-934
We examined the effects of angiotensin II (Ang II) on inward rectifier K+ currents (IK1) in rat atrial myocytes. [125I]Ang II-binding assays revealed the presence of both Ang II type 1 (AT1) and type 2 (AT2) receptors in atrial membrane preparations. Ang II inhibited IK1 in isolated atrial myocytes with an IC50 of 46 nmol/l. This inhibition was abolished by the AT, antagonist RNH6270 but not at all by the AT2 antagonist PD123319. Treatment of cells with pertussis toxin or a synthetic decapeptide corresponding to the carboxyl-terminus of Gialpha-3 abolished the inhibition by Ang II, indicating the role of a Gi-dependent signaling pathway. Accordingly, Ang II failed to inhibit IK1 in the presence of forskolin, dibutyryl-cAMP or protein kinase A catalytic subunits. In spite of the increased binding capacities for [125I]Ang II, Ang II failed to affect IKI in cells from spontaneously hypertensive rats (SHR). AT, immunoprecipitation from atrial extracts revealed decreased amounts of Gialpha-2 and Gialpha-3 proteins associated with this receptor in SHR as compared with controls. The reduced coupling of AT, with Gialpha. proteins may underlie the unresponsiveness of atrial IK1 to Ang II in SHR cells. 相似文献
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Cysts and tumors of the seminal vesicle are uncommon, and their coexistence is extremely rare. We report a case of multiple papillary tumors inside a seminal vesicle cyst associated with ipsilateral renal agenesis in a 17-year-old man. Surgical excision of the cyst and tumors was performed without any morbidity and histology revealed well differentiated papillary adenocarcinoma. 相似文献
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Results of low- and high-dose-rate interstitial brachytherapy for T3 mobile tongue cancer. 总被引:2,自引:0,他引:2
Naoya Kakimoto Takehiro Inoue Toshihiko Inoue Shumei Murakami Souhei Furukawa Ken Yoshida Yasuo Yoshioka Hideya Yamazaki Eiichi Tanaka Kimishige Shimizutani 《Radiotherapy and oncology》2003,68(2):123-128
PURPOSE: To evaluate the treatment results of low-dose-rate (LDR) and high-dose-rate (HDR) interstitial brachytherapy (ISBT) for T3 mobile tongue cancer. MATERIAL AND METHODS: Between 1974 and 1992, 61 patients with T3 mobile tongue cancer were treated with LDR ISBT using (192)Ir hairpins with or without single pins. In addition, between 1991 and 1999, 14 patients were treated with HDR ISBT. For nine patients treated with ISBT alone, the total dose was 59-94 Gy (median 72 Gy) within one week in LDR ISBT and 60 Gy/10 fractions/5 days in HDR ISBT. For 66 patients treated with a combination therapy of external beam radiotherapy (EBRT) and ISBT, the total dose was 12.5-60 Gy (median 30 Gy) of EBRT and 50-112 Gy (median 68 Gy) within 1 week in LDR ISBT or 32-60 Gy (median 48 Gy)/8-10 fractions/5-7 days in HDR ISBT. RESULTS: The 2- and 3-year local control rates of all patients were both 68%. The 2- and 3-year local control rates of patients treated with LDR ISBT were both 67%, and those with HDR ISBT were both 71%. The local control rate of patients treated with HDR ISBT was similar to those with LDR ISBT. CONCLUSIONS: ISBT for T3 mobile tongue cancer is effective and acceptable. The treatment result of HDR ISBT is almost similar to that of LDR ISBT for T3 mobile tongue cancer. 相似文献
100.
Takafumi Nagaoka Yoichi Katayama Toshikazu Kano Kazutaka Kobayashi Hideki Oshima Chikashi Fukaya Takamitsu Yamamoto 《Neuromodulation》2007,10(3):206-215
Objective. Employing [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) to assess the correlation between the effect of deep brain stimulation (DBS) on the subthalamic nucleus (STN) and the regional cerebral metabolic rate of glucose (rCMRGlc) in advanced Parkinson's disease patients (N = 8). Materials and Methods. On the basis of patients’ diary records, we performed FDG‐PET during the off‐period of motor activity with on‐ or off‐stimulation by STN‐DBS on separate days and analyzed the correlation between changes in motor symptoms and alterations in the rCMRGlc. Result. When FDG‐PET was performed, the motor score on the unified Parkinson's disease rating scale (UPDRS) was 64% lower with on‐stimulation than with off‐stimulation (p < 0.001, Wilcoxon single‐rank test). STN‐DBS increased the rCMRGlc in the posterior part of the right middle frontal gyrus, which corresponded to the premotor area, and the right anterior lobe of the cerebellum (p < 0.005, paired t‐test). No region exhibited a decrease in rCMRGlc. Among the items of the UPDRS motor score, the changes in resting tremor and rigidity of the left extremities showed a significant correlation with the changes in rCMRGlc observed in the right premotor area (p < 0.02 and p < 0.05, respectively, Spearman's rank correlation). Conclusions. STN‐DBS either activates the premotor area or normalizes the deactivation of the premotor area. These FDG‐PET findings obtained are consistent with the idea that STN‐DBS modifies the activities of neural circuits involved in motor control. 相似文献