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31.
Ali N Yoshizumi M Fujita Y Izawa Y Kanematsu Y Ishizawa K Tsuchiya K Yano S Sone S Tamaki T 《Journal of pharmacological sciences》2005,98(2):130-141
Vascular endothelial growth factor (VEGF) was reported to be a potent proangiogenic factor that plays a pivotal role in both physiological and pathological angiogenesis. M475271, 4-quinazolinamine, N-(2-chloro-5-methoxyphenyl)-6-methoxy-7-[(1-methyl-4-piperidinyl) methoxy]-(9Cl), is a new anilinoquinazoline derivative that showed selective inhibition of Src kinase activity and tumor growth in vivo. Here, we examined the effect of M475271 on VEGF-induced human umbilical vein endothelial cell (HUVEC) proliferation and migration and their intracellular mechanisms. Our findings showed that M475271 pretreatment resulted in a significant inhibition of VEGF-induced HUVEC proliferation, [(3)H]thymidine incorporation, and migration. M475271 inhibited VEGF-induced Flk-1 and Src phosphorylation and their association. Confocal laser microscopic examination confirmed the inhibitory effect of M475271 on VEGF-induced Flk-1/Src association. M475271 inhibited VEGF-induced extracellular signal-regulated kinase1/2 (ERK1/2) and p38 but not Akt activation in a concentration-dependent manner. M475271, PI3-K inhibitor, and p38 inhibitor inhibited VEGF-induced HUVEC proliferation and migration. However, a MEK1/2 inhibitor inhibited VEGF-induced proliferation but not migration. These findings suggest that M475271 attenuates VEGF-induced HUVEC proliferation and migration through the inhibition of signaling pathways involving Src, ERK1/2, and/or p38. Taken together, these data indicate that M475271 may be a useful candidate for inhibition of endothelial cell proliferation and migration relevant to angiogenesis. 相似文献
32.
33.
Ojanguren A Doenz F Qanadli SD Madoff DC Halkic N Bessoud B Denys A 《Journal of vascular and interventional radiology : JVIR》2005,16(7):1033-1036
Retained T-tubes are rare complications after biliary surgery. The authors present three cases of retained T-tubes in patients with transplanted liver that could not be removed by a standard manual traction. The authors describe a new simple percutaneous method that allows removal of these T-tubes without complication. 相似文献
34.
Denys A Lacombe C Schneider F Madoff DC Doenz F Qanadli SD Halkic N Sauvanet A Vilgrain V Schnyder P 《Journal of vascular and interventional radiology : JVIR》2005,16(12):1667-1674
PURPOSE: To describe the safety, complications, and liver regeneration associated with the left liver after embolization of the right portal vein (PV) in patients with hepatocellular carcinoma (HCC) developed in the setting of advanced liver fibrosis and cirrhosis. MATERIALS AND METHODS: Forty patients (31 men, nine women; mean age, 62 years) with HCC underwent PV embolization over a 4-year period. Embolization was performed from a left PV percutaneous access with use of n-butyl cyanoacrylate (NBCA) mixed with iodized oil. Computed tomography (CT) volumetry was performed before and 1 month after PV embolization to measure the left lobe volume as well as the functional liver ratio defined by the ratio between the left lobe and the total liver volume minus tumoral volume. PV pressure and liver enzyme levels were compared before and 1 month after the procedure and complications were registered. Factors potentially affecting regeneration (age, sex, diabetes, chemoembolization, functional liver ratio before PV embolization, and Knodell histologic score) were evaluated by one-way and stepwise regression analysis. RESULTS: PV embolization could be achieved successfully in all cases. Two patients had partial PV thrombosis on the 1-month follow-up CT and two patients developed transient ascites after PV embolization. The left lobe volume increase was 41% +/- 32% after PV embolization and the functional liver ratio increased from 28% +/- 10% to 36% +/- 10% (P < .0001). Hypertrophy of the left lobe was greater in patients with a low functional liver ratio before PV embolization and those with an F3 fibrosis score. Other factors had no influence on left lobe regeneration. CONCLUSION: PV embolization with use of NBCA is feasible in patients with advanced fibrosis and cirrhosis. Hypertrophy of the left lobe of the liver after PV embolization has a statistically significant correlation with lower functional liver ratio and lower degrees of fibrosis. 相似文献
35.
Hypercalcemia is a frequent finding in clinical practice. All possible causes must be considered in a patient with hypercalcemia. The association between both benign or malignant thyroid disease and primary hyperparathyroidism is well recognized. Up to 65% with primary hyperparathyroidism have associated thyroid abnormality. Hypercalcemia has also been associated with many malignant conditions. But, it is rarely seen in digestive tract cancer, such as carcinoma of gallbladder. Hypercalcemia syndrome is an absolutely rare entity. It is coexisting with hyperthyroidism, primary hyperparathyroidism and cancer of the gallbladder. 相似文献
36.
Tuncel D Yücesan C Erden E Savaş A Erden I Mutluer N 《Clinical neurology and neurosurgery》2005,107(3):249-252
Idiopathic hypertrophic cranial pachymeningitis (IHCP) consists of meningeal thickening due to chronic inflammation for which no cause such as infection, specific granulomatous disease, or malignancy is demonstrable. We present a case of IHCP with perifocal brain edema suggesting mass lesion with its magnetic resonance imaging (MRI) and pathologic findings. A 36-year-old woman was admitted to our hospital in August 2001 with a complaint of motor weakness in her left leg for 1 month. Magnetic resonance imaging with gadolinium revealed enhancement of the thickened dura mater and perifocal edema in the right frontoparietal region suggesting a mass lesion. Histological examination of the biopsy specimen revealed a dense fibrous cellular tissue. There was no obvious inflammatory infiltrate but in some areas between fibrous bundles one or two lymphocytes were detected. According to our knowledge, our patient is the second report in the literature of IHCP with focal edema causing a mass effect. 相似文献
37.
Yelmen KN 《The Tohoku journal of experimental medicine》2004,203(3):219-232
Acute hypoxia produces an increase in ventilation. When the hypoxia is sustained, the initial increase in ventilation is followed by a decrease in ventilation. Hypoxia causes changes in brain neurotransmitters depending on its severity and durations. The purpose of this study was to investigate the role of gamma-aminobutyric acid (GABA) and glutamate for hypoxic ventilatory response in rabbits. The experiments were performed in peripheral chemoreceptors intact and denervated rabbits anesthetized with Na-pentobarbitate. For intracerebroventricular (ICV) injections of reagents in each animal, cannula was placed in left lateral cerebral ventricle by stereotaxic method. After ICV injection of GABA (0.48 mg/kg), air breathing in both groups caused a depression of respiratory activity. On the other hand, after ICV injection of GABA, breathing of hypoxic gas mixture (8% O(2)-92% N(2)) in both groups produced the hypoxic hyperventilation. After ICV injection of GABA, blockade of GABA(A) receptors with bicuculline (0.2 mg/kg) did not prevent the hypoxic hyperventilation. In contrast, after ICV GABA injection, blockade of glutamate NMDA receptors with MK-801 (0.09 mg/kg) completely abolished the hypoxic hyperventilation observed while the animals were breathing hypoxic gas mixture. Our findings suggest that ICV injection of GABA causes respiratory depression in normoxic conditions, and that it increases ventilation in hypoxic conditions with or without peripheral chemoreceptor impulses by increasing glutamate. 相似文献
38.
Ali N Yoshizumi M Tsuchiya K Kyaw M Fujita Y Izawa Y Abe S Kanematsu Y Kagami S Tamaki T 《European journal of pharmacology》2004,485(1-3):127-135
Ebselen (2-phenyl-1, 2-benzisoselenazol-3[2H]-one) is a seleno-organic compound exhibiting both glutathione peroxidase and antioxidant activity. Although it has been reported that ebselen is effective against hydrogen peroxide (H(2)O(2))-induced cell death in several cell types, its effect on endothelial cell damage has not yet been elucidated. In the present study, we examined the effect of ebselen on H(2)O(2)-induced human umbilical vein endothelial cells (HUVECs) death, and its intracellular mechanism. Our findings showed that pretreatment of HUVECs with ebselen resulted in a significant recovery from H(2)O(2)-induced cell death in a concentration-dependent manner. In addition to the inhibition of lactate dehydrogenase (LDH) leakage, ebselen inhibited H(2)O(2)-induced cytochrome c release and caspase-3 activation and the resultant apoptosis in HUVECs. Moreover, it was observed that H(2)O(2) significantly stimulated activation of mitogen-activated protein (MAP) kinases, i.e., p38 MAP kinase, c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK1/2). Ebselen inhibited H(2)O(2)-induced p38 MAP kinase, but not JNK or ERK1/2 activation. Furthermore, SB203580 (4-[4-fluorophenyl]-2-[4-methylsulfinylphenyl]-5-[4-pyridyl]-1H-imidazole), a specific p38 MAP kinase inhibitor, inhibited H(2)O(2)-induced p38 MAP kinase phosphorylation, cytochrome c release, caspase-3 activation, as well as cell death in HUVECs. These findings suggest that ebselen attenuates H(2)O(2)-induced endothelial cell death through the inhibition of signaling pathways mediated by p38 MAP kinase, caspase-3, and cytochrome c release. Thus, inhibition of p38 MAP kinase by ebselen may imply its usefulness for prevention and/or treatment of endothelial cell dysfunction, which was suggested to be the first step in the development of atherosclerosis. 相似文献
39.
Kyaw M Yoshizumi M Tsuchiya K Kagami S Izawa Y Fujita Y Ali N Kanematsu Y Toida K Ishimura K Tamaki T 《Molecular pharmacology》2004,65(4):832-841
Angiotensin II (Ang II) plays an important role in several cardiovascular diseases associated with vascular smooth muscle cell (VSMC) growth and migration. Src activity is known to be required for the migration of a number of cell types. p130Cas was reported to be essential for cell migration and actin filament reorganization. Mitogen-activated protein (MAP) kinases were also reported to be critical regulatory factors for growth and migration of VSMC. However, precise intracellular mechanisms involving c-Src, p130Cas, and MAP kinases in Ang II-stimulated migration of VSMC have not been well elucidated. Here we demonstrated that Ang II rapidly and significantly stimulated tyrosine phosphorylation of Src and Cas and their association in rat aortic smooth muscle cells (RASMC). Ang II-stimulated tyrosine phosphorylation of Src and Cas and activation of ERK1/2 and JNK, but not p38, were potently inhibited by Src family tyrosine kinase inhibitors, herbimycin A (HA) and PP2. Ang II-stimulated Src and Cas association, tyrosine phosphorylation of Cas, and activation of ERK1/2 and JNK were suppressed in kinase-inactive Src (KI Src)-overexpressed RASMC. Ang II-stimulated JNK activation but not ERK1/2 activation was blocked in substrate domain-deleted Cas (DeltaSD Cas)-overexpressed RASMC. In addition, HA, PP2, ERK1/2 inhibitor, 2'-amino-3'-methoxyflavone (PD98059) and JNK inhibitor, and anthra[1,9-cd]pyrazol-6(2H)-one (SP600125) significantly inhibited Ang II-stimulated migration of RASMC. Ang II-induced colocalization of Src and Cas and migration were inhibited in both KI Src- and DeltaSD Cas-overexpressed RASMC. These findings suggest that Src and Cas are essentially but differentially involved in Ang II-stimulated migration of VSMC through the activation of ERK1/2 and JNK. 相似文献
40.
Vascular wall damage in rats induced by methidathion and ameliorating effect of vitamins E and C 总被引:2,自引:0,他引:2
Yavuz T Delibas N Yildirim B Altuntas I Candir O Cora A Karaman N Ibrisim E Kutsal A 《Archives of toxicology》2004,78(11):655-659
We examined the effect of subacute methidathion (MD) administration on vascular wall damage and evaluated the ameliorating effects of combination of vitamins E and C against MD toxicity. The experimental groups were: rats treated with corn oil (control group), rats treated with 5 mg/kg MD (MD), and rats treated with 5 mg/kg body weight MD plus vitamin E and vitamin C (MD+Vit). The groups were given MD by gavage on 5 days a week for 4 weeks at a daily dose 5 mg/kg (MD and MD+Vit) using corn oil as the vehicle. Vitamins E and C were injected at doses of 50 mg/kg intramuscularly and 20 mg/kg intraperitoneally, respectively, after the treatment with MD in the MD+Vit group. The levels of malondialdehyde (MDA) were determined in the aortic tissue. Histopathological examination was examined in the thoracic aortic tissue. MDA levels were higher in the MD group than the control group and lower in the MD+Vit group than MD group. MD administration led to irregulation, prominent breaks, and fragmentation of the elastic fibers but decrease in the irregulation and fragmantation of the elastic fibers with the combination of vitamins E and C in MD-treated rats. In conclusion, it is likely that subacute MD administration caused vascular wall damage, and that treatment with a combination of vitamins E and C after the administration of MD can reduce vascular wall damage caused by MD. 相似文献