高脂血症对兔动脉壁一氧化氮系统的影响及药物的干预效果

将雄性纯种新西兰家兔36只随机分为三组,喂饲胆固醇形成实验性高胆固醇血症,部分加用麝香保心丸喂养;同时采用定量RT-PCR等技术,观察高脂血症对动脉壁一氧化氮系统代谢的影响,以及麝香保心丸的保护作用.结果表明:高脂饮食可造成动脉一氧化氮代谢的紊乱,降低动脉壁内皮型一氧化氮合酶(eNOS)基因的表达(P相似文献   

Mortality and morbidity of diabetes in Papua New Guinea

Summary A 95% follow-up of all known diabetic patients in one racial group in Papua New Guinea was performed. Mortality was high with an average life-span of 4–5 years from the time of diagnosis. Microvascular diabetic complications were detected in over half of the surviving diabetic patients whose average duration of known disease was 3.8 years. At present, diabetes mellitus is both a rapidly fatal and morbid disease in Papua New Guinea.     

兔腹主动脉粥样硬化支架植入后血管壁及内膜改变

目的通过建立兔腹主动脉粥样硬化植入支架动物模型,探讨支架植入后血管壁和内膜变化及发生机制.方法采用兔腹主动脉内膜剥脱术加含1.5%高胆固醇的高脂饮食来建立动脉粥样硬化动物模型,并在此基础上建立兔粥样硬化腹主动脉植入支架模型,并通过组织病理学检查,来揭示支架植入后血管壁和内膜组织形态学变化和病变的发生机制.结果在动脉粥样的动物模型基础上所建立兔腹主动脉粥样硬化植入支架动物模型,经组织形态学和免疫组化检查显示:动物模型目标血管段管腔内膜明显增厚、血管出现不同程度的狭窄,新生内膜中有大量增殖细胞核抗原(PCNA)高表达(着色强度IS:5.268±0.475)的血管平滑肌细胞(VSMC)和泡沫细胞及细胞外基质(ECM).经计算机图像分析仪测定其组织形态学指标分别为残余管腔面积[(9.67±0.18)mm2]、最大内膜厚度[(1.33±0.05)mm]、内膜面积[(5.78±0.23)mm2]和狭窄程度[(31.02±1.91)%].结论本实验成功地建立了兔腹主动脉粥样硬化植入支架动物模型,并认为支架术后血管新生内膜中VSMC过度增殖是导致支架植入后管腔内膜明显增厚的可能原因.     

Glucose inhibits replication of cultured human endothelial cells

Summary Diabetes is an important risk factor for atherosclerosis but the mechanism of the risk is unknown. As endothelial injury is considered to be an early event in the development of atherosclerosis, the effect of glucose on endothelial cell replication was studied. Concentrations of glucose of 11.2, 16.8 and 22.4 mmol/l inhibited DNA synthesis in cultured human umbilical venous endothelial cells by 8.1±10.8, 24.3±8.8 and 30.9±7.4%, respectively. Glucose also inhibited the proliferative response of endothelial cells to experimental wounds in the cell layer. Sorbitol (22.4 mmol/l) inhibited endothelial cell DNA synthesis by 50±13.6%, but mannitol (22.4 mmol/l) inhibited DNA synthesis by only 3±24.3%. It is suggested that in diabetic subjects, high blood glucose levels may cause endothelial injury, or inhibit its repair, and hence allow the exposure of the arterial media to plasma and its constituents.     

Platelet activation in normo- and hyperlipoproteinemias

Summary In the last few years it became obvious that platelets are involved in the development of atherosclerotic diseases. This involvement of platelets has been taken into account in the response to injury hypothesis of atherosclerosis. The hypothesis is based on the assumption that atherosclerotic lesions result from endothelial injury, followed by the interaction of, vessel wall constituents with lipoproteins, macrophages, and platelets.In the first part of this review, general aspects of platelet activation are summarized and the pathways of platelet aggregation as well as their involvement in blood coagulation are discussed.The second part of this paper describes the influence of cholesterol, lipoproteins, and apolipoproteins upon the activation and metabolic behavior of, platelets. Physiological and pathophysiological processes particularly occurring in different types of hyperlipoproteinemias and atherosclerotic disorders are discussed in this context.     

Pilot Results of the Early Detection by Ultrasound of Carotid Artery Intima-Media Thickness Evaluation (EDUCATE) study

BACKGROUND: Limitations of current models for risk stratification are known. Noninvasive imaging is being advocated as an adjunct to improve risk prediction; however, studies documenting outcomes are rare. Therefore, we aimed to evaluate the negative and positive predictive values of carotid atherosclerosis for future cardiovascular events. METHODS: The Early Detection by Ultrasound of Carotid Artery intima media Thickness Evaluation (EDUCATE) study prospectively enrolled 253 consecutive young to middle-aged adults undergoing elective coronary angiography. Bilateral carotid ultrasound and lipid profiles were performed. Carotid atherosclerosis was defined as intima media thickness >/=1.0 mm in the main body, or focal plaque within the body, bulb, or proximal branch. Future events included major (death, myocardial infarction, stroke) and minor (revascularization and new onset heart failure). RESULTS: Of the enrolled patients 236 completed all tests; mean age was 51 +/- 8 years; 58% women. Sensitivity, specificity, and negative predictive values for carotid atherosclerosis in predicting severe coronary artery disease were 72%, 49% and 79%, with an odds ratio (OR) of 2.2 (95% confidence interval [CI] 1.2-4.0). Of patients suffering major events, 90% had carotid atherosclerosis. Only 1 of 95 without carotid atherosclerosis experienced a major event. Kaplan-Meier analysis revealed differences in event-free survival in favor of subjects without carotid atherosclerosis for major (P = .051) and any event (P = .015). Cox analysis revealed a hazard ratio (HR) of 2.7 (95% CI 1.2-6.2; P = .020) for predicting future events. The relationship remained significant after adjusting for traditional risk factors (HR 2.5, 95% CI 1.1-5.9; P = .034). CONCLUSIONS: Carotid atherosclerosis is associated with severe coronary artery disease and future events. Negative carotid ultrasound is associated with excellent prognosis.     

DWI阴性的急性缺血性卒中患者的临床特点和原因分析

目的探讨弥散加权成像(diffusion weighted imaging,DWI)阴性的急性缺血性卒中患者的临床特点、影像学表现、病因。方法回顾性分析自2012年1月~2014年7月首都医科大学附属北京天坛医院神经内科急诊溶栓绿色通道就诊的DWI阴性的疑似急性缺血性卒中患者,收集其人口学特征、临床表现、影像数据,进行病因学分类。结果连续收集134例溶栓医生初步判断为DWI阴性的疑似急性缺血性卒中患者,其中男性90例,女性44例,中位数年龄57岁(四分位数间距50~70),从发病到完成DWI检查的中位数时间266.5 min(四分位数间距205.3~362.5)。中位数美国国立卫生研究院卒中量表(National Institutes of Health Stroke Scale,NIHSS)评分2(四分位数间距1~3)。33例患者住院进一步诊治。有27例(81.8%)被诊断为缺血性卒中,另有6例(18.2%)诊断为其他疾病。27例诊断为缺血性卒中的住院患者中,9例(33.3%)经重新读片后发现缺血灶,5例(18.5%)症状加重后复查出现缺血灶,1例(3.7%)未加重但复查出现缺血灶,1例(3.7%)症状加重后复查DWI仍无缺血灶但有可以解释症状的磁共振血管成像(magnetic resonance angiography,MRA)大血管闭塞/狭窄或灌注加权成像(perfusion weighted imaging)低灌注区,6例(22.2%)虽DWI阴性但MRA有可以解释症状的大血管闭塞/狭窄或PWI有低灌注区,5例(18.5%)DWI阴性且未见大血管异常。诊断为缺血性卒中的27例患者,根据急性卒中治疗低分子肝素试验病因分型法(Trial of Org 10172 in Acute Stroke Treatment,TOAST)的分型标准,15例(55.6%)为大动脉粥样硬化,11例(40.7%)为小动脉闭塞,1例(3.7%)病因不明。住院患者中,除1例(3.0%)患者出院时明显残疾外,其余32例(97.0%)患者出院时结局良好。101例患者在急诊治疗后出院。其中80例(79.2%)DWI阴性且未见其他异常,5例(5.0%)经重新读片后发现缺血灶,14例(13.9%)虽DWI阴性但MRA有可以解释症状的大血管闭塞/狭窄或PWI低灌注区修正诊断为缺血性卒中,2例(2.0%)诊断为其他疾病。结论 DWI阴性的急性缺血性卒中,多数为小卒中。大动脉粥样硬化性闭塞/狭窄和小动脉闭塞是主要病因。在急诊溶栓绿色通道中,溶栓医生初步判断为DWI阴性的疑似急性缺血性卒中患者,存在读片遗漏、显影延迟的可能和病情加重的风险。     

急性脑梗死患者同型半胱氨酸与颈动脉斑块的相关性研究

目的探讨急性脑梗死患者血清同型半胱氨酸(homocysteine,HCY)与颈动脉斑块的关系。方法回顾性分析北京朝阳医院西区2013年6月~2014年6月神经内科住院的急性脑梗死患者196例,通过彩色多普勒超声仪测定颈动脉粥样硬化斑块的有无,测定内中膜厚度及其最大斑块厚度。在发病4 d内检测其血清HCY浓度。患者按照有无斑块分为斑块组(n=152)和无斑块组(n=44)。组间比较采用秩和检验,HCY与颈动脉斑块最大厚度的关系采用Spearman秩相关检验。颈动脉斑块形成的危险因素分析采用Logistic回归分析。结果无斑块组(n=44)的HCY中位数是11.6μmol/L,斑块组(n=152)的HCY的中位数是14.0μmol/L,秩和检验P=0.011。Spearman相关检验发现HCY与颈动脉最大斑块厚度呈显著正相关,相关系数r=0.247,P0.001。Logistic回归分析,发现年龄[比值比(odds ratio,OR)1.089,95%可信区间(confidence interval,CI)1.050~1.131,P=0.0001]、男性性别(OR 4.304,95%CI 1.738~10.660,P=0.002)、高血压史(OR 3.864,95%CI 1.750~8.534,P=0.001)是影响斑块形成的独立危险因素,而HCY(OR 1.026,95%CI 0.973~1.081,P=0.344)对斑块形成的影响无显著性。但是,对于非心源性脑梗死亚组(n=183)分析发现HCY是斑块形成的独立危险因素(OR 1.267,95%CI 1.006~1.430,P=0.003)。结论对于急性脑梗死患者,斑块组血清HCY高于无斑块组,血清HCY与颈动脉最大斑块厚度呈正相关。在非心源性脑梗死患者中HCY是颈动脉斑块形成的独立危险因素。     

Glycolaldehyde and maleyl conjugated human serum albumin as potential macrophage‐targeting carriers for molecular imaging purposes

Maleylated bovine serum albumin is a known ligand for targeting macrophages and has potential as a carrier for molecular imaging purposes. We present a novel synthesis of glycolaldehyde‐conjugated human serum albumin (GA‐HSA) and maleylated human serum albumin (Mal‐HSA). Seventeen modifications of fluorescently tagged GA‐HSA and Mal‐HSA molecules with different degrees of conjugation were prepared. The comparative uptake studies, using 12 of these modifications, were done in vitro on mouse monocytes/macrophages (RAW264.7), and evaluated qualitatively by confocal microscopy and quantitatively by flow cytometry. The GA modifications are taken up by the macrophages approximately 40% better than the maleyl modifications at low concentrations (≤3 μm ), while at higher concentrations it appears that the maleyl modifications are taken up around 25–44% better than the GA‐modified HSA. However, high uptake at low concentrations will be beneficial for in vivo localizing inflammation in areas with low penetration of the probe as in an atherosclerotic plaque. Further, another advantage of GA‐HSA is that GA competes less than the maleyl group for the free reactive amine sites that are to be used for conjugation of metal chelating ligands (e.g. tetraazacyclododecanetetraacetic acid and triazacyclononanetriacetic acid). Metal ions such as Gd³⁺ and Mn²⁺ can be chelated for positive Magnetic Resonance (MR) contrast and positron emitting ions such as ⁶⁴Cu²⁺ and ⁶⁸Ga³⁺ for Positron Emission Tomography (PET) imaging. These are important properties, especially, when considering the MR contrast possibilities owing to the low sensitivity of the technique, and would motivate the use of GA‐HSA before Mal‐HSA. © 2014 The Authors. Contrast Media & Molecular Imaging published by John Wiley & Sons, Ltd.     

超敏C反应蛋白与2型糖尿病患者动脉粥样硬化的相关性研究

目的探讨血清超敏C反应蛋白(hs-CRP)与2型糖尿病患者颈动脉粥样硬化的相关性。方法收集83例2型糖尿病患者和40例体检健康者血清,根据患者血清低密度脂蛋白胆固醇(LDL-C)水平将糖尿病组患者分为LDL-C水平增高组和LDL-C水平正常组,测定所有受检者血清hs-CRP水平及糖尿病患者颈动脉内膜中层厚度(IMT)。结果 hs-CRP水平在LDL-C增高组、正常组及对照组之间呈逐渐下降趋势,两两比较,差异具有统计学意义(P0.01);hs-CRP浓度与LDL-C浓度呈正相关(r=0.4781,P0.05);2型糖尿病患者中合并颈动脉粥样硬化者血清hs-CRP阳性率明显高于无颈动脉病变者(P0.01)。结论 2型糖尿病患者血清hs-CRP水平显著升高,且与患者LDL-C浓度及颈总动脉粥样硬化形成有一定的相关性。