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PNPLA3 gene polymorphism and response to lifestyle modification in patients with nonalcoholic fatty liver disease 下载免费PDF全文
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Tien‐Yao Tsai Iat‐Lon Leong Ka‐Shun Cheng Lian‐Ru Shiao Tzu‐Hui Su Kar‐Lok Wong Paul Chan Yuk‐Man Leung 《Fundamental & clinical pharmacology》2019,33(1):52-62
A pathological feature in atherosclerosis is the dysfunction and death of vascular endothelial cells (EC). Oxidized low‐density lipoprotein (LDL), known to accumulate in the atherosclerotic arterial walls, impairs endothelium‐dependent relaxation and causes EC apoptosis. A major bioactive ingredient of the oxidized LDL is lysophosphatidylcholine (LPC), which at higher concentrations causes apoptosis and necrosis in various EC. There is hitherto no report on LPC‐induced cytotoxicity in brain EC. In this work, we found that LPC caused cytosolic Ca2+ overload, mitochondrial membrane potential decrease, p38 activation, caspase 3 activation and eventually apoptotic death in mouse cerebral bEND.3 EC. In contrast to reported reactive oxygen species (ROS) generation by LPC in other EC, LPC did not trigger ROS formation in bEND.3 cells. Pharmacological inhibition of p38 alleviated LPC‐inflicted cell death. We examined whether heparin could be cytoprotective: although it could not suppress LPC‐triggered Ca2+ signal, p38 activation and mitochondrial membrane potential drop, it did suppress LPC‐induced caspase 3 activation and alleviate LPC‐inflicted cytotoxicity. Our data suggest LPC apoptotic death mechanisms in bEND.3 might involve mitochondrial membrane potential decrease and p38 activation. Heparin is protective against LPC cytotoxicity and might intervene steps between mitochondrial membrane potential drop/p38 activation and caspase 3 activation. 相似文献
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F Boomsma F A van der Hoorn A J Man in 't Veld M A Schalekamp 《Clinica chimica acta; international journal of clinical chemistry》1988,178(1):59-69
We report a reliable method for determining DOPA levels in plasma and cerebrospinal fluid. The method is based on complete conversion of DOPA to dopamine and quantification by HPLC-ECD of the dopamine formed. Lower limit of detection was 0.5 nmol/l. No differences in plasma DOPA levels were found between normal children (0-15 yr, n = 60), normal adults (n = 39) and patients with essential hypertension (n = 40) or Parkinson's disease (no DOPA therapy, n = 30). In normal individuals and in patients with essential hypertension venous plasma levels were higher than arterial levels (10.2 vs 9.3 nmol/l, p less than 0.001, V/A ratio 1.11 (SD 0.08), n = 15). Sympathetic stimuli (standing, tilting, bicycle exercise, tyramine) did not influence DOPA levels. In untreated depressed patients (n = 10) and in non-parkinsonian neurological patients (n = 12) cerebrospinal fluid levels of DOPA were 4.5 (SD 2.4) and 5.2 (SD 1.3) nmol/l respectively. A direct method for the measurement of DOPA by HPLC-ECD after deproteinization of plasma is also described and compared with the conversion method. Good agreement was found when plasma DOPA levels exceeded 0.25 mumol/l (y(conversion method) = 0.943x (direct method) + 0.118; n = 60; r = 0.985). The direct method, because of greater simplicity and the possibility of simultaneous measurement of the DOPA metabolite 3-O-methyldopa, is the method of choice with plasma samples from DOPA-treated patients. In non-DOPA treated individuals the conversion method is superior and has proved to be an accurate and sensitive method for the determination of DOPA levels in plasma and cerebrospinal fluid. 相似文献
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胰岛素瘤的超声诊断:与其他诊断方法比较 总被引:1,自引:0,他引:1
目的:探讨超声等方法对胰岛素瘤的定位诊断价值。材料和方法:对42例经过手术和病理证实的胰岛素瘤患者术前定位诊断的各种方法进行回顾性分析,并与其他诊断方法对比分析其各自的定位符合率。结果:定位诊断符合率分别为B超31%(13/42)、EUS55.6%(5/9)、IOUS100%(10/10)、超声引导下PTPC100%(3/3)、CT59.5%(25/42)、MRI50%(6/12)、选择性DSA27.3%(3/11)及ASVS90%(9/10)。彩超(CDUS)对胰岛素瘤良、恶性有鉴别作用。结论:遵循循序渐进原则,先后选用B超(含CDUS)、EUS、CT等已可解决80%以上的定位诊断,然后再做MRI及ASVS;对仍未作出定位者,只要定性诊断明确即有手术探查指征,因为IOUS能提供可靠的定位信息。 相似文献