Clinical outcomes after percutaneous coronary intervention for early versus late and very late stent thrombosis: a systematic review and meta-analysis

Journal of Thrombosis and Thrombolysis - Whether the clinical outcomes of stent thrombosis (ST) are different when stratified by time of occurrence remains unclear. The objective of this study was...     

Fas/FasL、Bcl-2/Bax、Caspase-8在大鼠非酒精性脂肪性肝病中的作用机制

目的:探讨肝细胞凋亡及其相关因素Fas/FasL、Bcl-2/Bax蛋白及Caspase-8 mRNA的表达在大鼠非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)中的作用.方法:采用改良高脂饮食建立大鼠NAFLD模型,以正常饮食设立对照组.HE染色观察肝脏脂肪变、炎症活动和纤维化程度,采用流式细胞仪法测肝细胞凋亡百分数;免疫组织化学法检测Fas、FasL、Bcl-2及Bax在肝组织中表达情况;实时荧光定量PCR法检测肝脏Caspase-8 mRNA的表达.结果:NAFLD模型组脂肪变性明显,纤维化和炎症活动度记分均显著高于正常对照组.流式细胞仪检测显示,与对照组比较,实验组大鼠肝细胞凋亡百分数增加,随造模时间延长凋亡率增加更明显(均P<0.01);免疫组织化学染色显示随着肝脏脂肪变加重,Fas、FasL蛋白染色加深,阳性细胞数增加;Bcl-2、Bax在对照组的表达均为散在弱阳性,实验组4、8、12wk阳性细胞数渐增加,并在脂肪变明显的部位着色深且随着脂肪肝的进展,Bcl-2/Bax比率进行性下降.实时荧光定量PCR法显示Caspase-8 mRNA表达量在高脂组中显著高于对照组(均P<0.01),且随肝脏脂肪变及炎症加重呈进行性上升.结论:在NAFLD发生过程中,肝细胞凋亡促进NAFLD大鼠病情进展;Fas、FasL、Caspase-8 mRNA相关调控蛋白的活化是引起NAFLD脂肪变性、炎症及纤维化的重要因素.细胞凋亡调节蛋白Bax、Bcl-2表达上调,二者表达的相对比例发生异常,这可能是NAFLD中肝细胞发生凋亡的重要原因之一.     

Effect of calcitonin gene-related peptide on angiotensin II-induced proliferation of rat vascular smooth muscle cells

The present study was designed to examine the effect of calcitonin gene-related peptide (CGRP) on angiotensin II-induced proliferation of cultured rat vascular smooth muscle cells. Vascular smooth muscle cells were grown from explants of Sprague-Dawley rat aorta. Vascular smooth muscle cells (between passages 5 and 10) were incubated with 0.1% neonatal calf serum for 48 h, and then treated with angiotensin II (100 nM) in the absence or presence of CGRP for 24 h. The viability, DNA synthesis and cell cycle of vascular smooth muscle cells were measured. Western blotting was used to determine the activity of intracellular extracellular regulated kinase (ERK1/2). Angiotensin II significantly decreased the viability and proliferation of vascular smooth muscle cells, decreased the proliferation index, and increased the activity of ERK1/2; the effects of angiotensin II were inhibited by CGRP (1-100 nM) in a concentration-dependent manner. In conclusion, CGRP significantly inhibits angiotensin II-induced proliferation of vascular smooth muscle cells, an effect related to a decrease in the activation of mitogen-activated protein kinase pathway.     

The protective effects of ligustrazine on ischemia-reperfusion and DPPH free radical-induced myocardial injury in isolated rat hearts

Previous investigations have suggested that tumor necrosis factor-alpha (TNF-alpha) can contribute to myocardial damage during ischemia-reperfusion. In the present study, we examined whether the cardioprotective effects of ligustrazine are related to inhibition of TNF-alpha production in the rat models of ischemia-reperfusion and 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical-induced myocardial injury. Ischemia for 20 min and reperfusion for 40 min caused a decline in cardiac function (left ventricular pressure, +/- d p/d t(max), heart rate and coronary flow) and an increase in the release of creatine kinase in coronary effluent and the content of TNF-alpha in myocardial tissues. Similarly, perfusion with DPPH (100 nM) for 30 min significantly decreased cardiac function, and increased the release of creatine kinase and the content of TNF-alpha. Ligustrazine at the concentration of 40 or 80 mg/L markedly improved cardiac function and reduced the release of creatine kinase and the content of TNF-alpha in myocardial tissues in hearts subjected to ischemia-reperfusion or DPPH perfusion. These results suggest that the cardioprotection afforded by ligustrazine is related to a reduction of TNF-alpha content by inhibition of free radical production in isolated rat hearts.     

Inhibition of experimental autoimmune anterior uveitis by adenovirus-mediated transfer of the interleukin-10 gene.

AIMS: The aim of this study was to investigate the efficiency of adenoviral-mediated transfer of the interleukin (IL)-10 gene for inhibition of experimental autoimmune anterior uveitis, a rat model of human acute anterior uveitis. Uveitis was induced in the Lewis rat by simultaneous injection of melanin-associated antigen intraperitoneally (i.p.) and into the left footpad. The animals were treated by systemic administration of adenoviral construct expressing IL-10 (Ad-IL-10) or Ad-Mock carrying no cytokine transgene. RESULTS: A significant reduction in ocular inflammation was noted for rats that received one or two divided i.p. administrations of Ad-IL-10 (one 10 x 10(9) and two 5 x 10(9) particles of adenoviral construct, respectively), as judged by reduced clinical scores and decreased leukocyte infiltration in the anterior chamber and confirmed by histological examinations, relative to control animals. Systemic Ad-IL-10, treatment also revealed a higher serum level of IL-10, compared to the controls. CONCLUSIONS: The results suggest that systemic adenovirus-mediated IL-10 gene therapy has an anti-inflammatory effect on immune-mediated ocular inflammation and that this approach may be promising for the treatment of acute anterior uveitis.     

1型糖尿病大鼠骨髓内皮祖细胞衰老与非对称二甲基精氨酸浓度升高有关

目的研究非对称二甲基精氨酸与1型糖尿病大鼠骨髓内皮祖细胞衰老之间的关系。方法单次腹腔注射链脲佐菌素(65 mg/kg)建立1型糖尿病大鼠模型,检测血糖、骨髓内皮祖细胞衰老、血浆非对称二甲基精氨酸水平以及内皮祖细胞中二甲基精氨酸-二甲胺水解酶2和SIRT1的mRNA表达。结果与对照组比较,糖尿病大鼠血浆非对称二甲基精氨酸水平显著升高(0.67±0.06μmol/L比0.55±0.07μmol/L)、内皮祖细胞衰老率增加(39%±8%比11%±2%)、二甲基精氨酸-二甲胺水解酶(0.56±0.17比1.00±0.22)和SIRT1(0.08±0.17比1.00±0.39)的mRNA表达下调。结论糖尿病大鼠内皮祖细胞衰老与非对称二甲基精氨酸水平升高有关,其机制可能涉及SIRT1/二甲基精氨酸-二甲胺水解酶2途径。     

Metabolism of high density lipoproteins in liver cancer

Liver plays a vital role in the production and catabolism of plasma lipoproteins. It depends on the integrity of cellular function of liver, which ensures homeostasis of lipid and lipoprotein metabolism. When liver cancer occurs these processes are impaired and high-density lipoproteins are changed.     

Relationship between protective effects of rosiglitazone on endothelium and endogenous nitric oxide synthase inhibitor in streptozotocin-induced diabetic rats and cultured endothelial cells

BACKGROUND: Previous investigations have indicated that the level of asymmetric dimethylarginine (ADMA) is increased in diabetic patients and animals, and rosiglitazone has a protective effect on the endothelium. In the present study, we tested the relationship between protective effects of rosiglitazone and ADMA in streptozotocin (STZ)-induced diabetic rats and cultured endothelial cells. METHODS: Blood samples were collected from carotid artery. Vasodilator responses to acetylcholine (ACh) in the isolated aortic rings were measured, and serum concentrations of glucose, lipid, nitrite/nitrate, ADMA and tumour necrosis factor-alpha (TNF-alpha) were determined. Cultured endothelial cells were treated with ADMA, and the concentrations of intercellular adhesion molecule (ICAM-1), TNF-alpha, and the activity of nuclear factor-kappaB (NF-kappaB) were determined. RESULTS: Vasodilator responses to ACh were decreased markedly and the serum concentrations of TNF-alpha, nitrite/nitrate and ADMA were increased significantly in diabetic rats. Rosiglitazone (3, 10 or 30 mg/kg) produced a significant reduction of the inhibition of vasodilator responses to ACh, but had no effect on the serum concentrations of glucose, lipid, nitrite/nitrate and ADMA in diabetic rats. ADMA (30 microM) significantly increased the activity of NF-kappaB and elevated the levels of ICAM-1 and TNF-alpha, and pre-treatment with rosiglitazone (10 or 30 microM) markedly inhibited the increased activity of NF-kappaB and reduced the elevated levels of TNF-alpha and ICAM-1 induced by ADMA in cultured endothelial cells. CONCLUSIONS: Rosiglitazone improves endothelial function in diabetic rats, which is related to the reduction of the inflammatory response induced by ADMA.     

Visual outcome in primary macula-off rhegmatogenous retinal detachment treated with scleral buckling.

BACKGROUND AND PURPOSE: To evaluate the visual outcome of primary macula-off rhegmatogenous retinal detachment after successful scleral buckling. METHODS: A retrospective, non-controlled case series study was conducted in 93 patients (93 eyes) who underwent primary successful scleral buckling procedure for retinal detachment. Factors including duration of macular detachment, patient age, preoperative best-corrected visual acuity (VA), surgical management of subretinal fluid, and refractive error were analyzed statistically to determine their association with final visual outcome. RESULTS: Postoperative VA of 20/50 or better was found in 53.6% of eyes with duration of macular detachment within 7 days, and 29.7% of eyes with macular detachment for more than 7 days (Fisher's exact test, p = 0.019). VA better than 20/50 was found in 61% of eyes with preoperative VA better than 20/400 and in 33.9% with preoperative VA worse than 20/400 (Fisher's exact test, p = 0.008). Patients aged 30 years or less achieved better mean postoperative VA than those aged 31 to 50 and those aged 50 years and older (ANOVA, p = 0.003). Patients with low-grade myopia (< -6D) regained significantly better mean postoperative VA as compared with high myopia (> -6D) and emmetropic eyes (0 to +3D) (ANOVA, p < 0.001). Subretinal fluid drainage procedure did not affect postoperative visual result. Multivariate logistic regression analysis revealed that the duration of macular detachment was the only variable affecting the visual result. CONCLUSION: Scleral buckle surgery performed within the first week, preoperative vision more than 20/400, age younger than 30 years old, and low-grade myopia were associated with significantly better visual recovery from macular-off rhegmatogenous retinal detachment.