同型半胱氨酸与糖尿病微血管病变的相关性及药物干预后的变化

目的探讨同型半胱氨酸与糖尿病微血管病变的相关性及药物干预后的变化。方法2型糖尿病患者200例,根据患者微 血管并发症情况分为无微血管病变组和合并微血管病变组,所有患者治疗前及治疗6个月后进行血脂、血糖、肾功能及血清同 型半胱氨酸测定。另外按年龄和性别匹配的原则选择同期进行体检的健康受试者100例作为正常对照组。结果（1）无血管病 变组和合并微血管病变组患者常规测量收缩压（SBP）、舒张压（DBP）、甘油三酯（TG）、血脂测定包括总胆固醇（TC）、低密度脂 蛋白（LDL）、血糖测定包括空腹血糖（FBG）、餐后2 h 血糖（2 h PBG）、糖化血红蛋白（HbA1）、肾功能测定包括血清尿素氮 （SUN）、血清肌酐（Scr）和血浆同型半胱氨酸（HCY）水平均显著高于正常对照组（P<0.01）,HDL水平显著低于正常对照组（P< 0.01）;（2）合并微血管病变组患者的SBP、DBP、SUN、SCr和HCY水平显著高于无血管病变组（P<0.01）;（3）多因素logistic回归 分析显示舒张压、尿素氮、血清肌酐和同型半胱氨酸水平是糖尿病患者发生微血管并发症的危险因素;（4）治疗后无微血管病变 组和合并微血管病变组组患者HCY水平均较治疗前显著降低（P<0.01）。结论高同型半胱氨酸水平是糖尿病微血管病变的高 危因素,经治疗后可降低患者同型半胱氨酸水平。     

痛风病人同型半胱氨酸和炎症指标的病例对照研究

目的探讨痛风与同型半胱氨酸和炎症指标关系。方法采用频数匹配1∶1病例对照研究方法,病例组和对照组各调查379例。调查收集研究对象的基本信息、饮酒、疾病史,测量身高、体重,测定血常规、尿酸、同型半胱氨酸、超敏C-反应蛋白。结果经单因素分析发现年龄、职业、文化、收入、痛风家族史、BMI、血小板、中性粒细胞、白细胞、尿酸、同型半胱氨酸、超敏C反应蛋白暴露率与痛风有关(P0.01);≥3个关节痛风的尿酸、同型半胱氨酸,中性粒细胞、白细胞水平高于3个关节痛风(P0.01或0.05)。二分类logistic回归分析发现,在控制年龄、职业、文化等个体特征因素后,尿酸、同型半胱氨酸、超敏C反应蛋白是痛风的危险因素。其中高尿酸血症与非高尿酸血症相比OR值为4.3(95%CI,2.9~6.4);同型半胱氨酸15.0μmol/L和30.0μmol/L与≤15.0μmol/L相比OR值分别为2.9(95%CI,1.9~4.2)和5.6(95%CI,2.4~13.2);超敏C反应蛋白≥3.0 mg/L和≥10.0 mg/L与3.0 mg/L相比OR值为2.4(95%CI,1.6~3.7)和5.1(95%CI,2.8~9.1);同时检测尿酸、同型半胱氨酸、超敏C反应蛋白ROC曲线AUC最大(P0.01)。多分类回归分析发现高尿酸血症与非高尿酸血症相比,≥3个关节痛风OR值为10.0(95%CI,4.2~24.0);同型半胱氨酸15.0μmol/L和30.0μmol/L与≤15.0μmol/L相比,≥3个关节痛风OR值分别为7.8(95%CI,3.5~17.4)和23.2(95%CI,7.1~76.3);超敏C反应蛋白≥3.0 mg/L和≥10.0 mg/L与3.0 mg/L相比,≥3个关节痛风OR值为2.5(95%CI,1.3~4.9)和7.2(95%CI,3.2~16.3)。结论尿酸、同型半胱氨酸、超敏C反应蛋白是痛风的危险因素,并与疾病的严重程度有关。     

血浆同型半胱氨酸与急性脑梗死后认知功能障碍的相关性研究

目的:探讨血浆同型半胱氨酸（Hcy）水平对急性脑梗死后认知功能障碍的影响。方法:连续纳入急性脑梗死患者228例,根据蒙特利尔认知评估量表的评估结果分为无认知障碍组和认知障碍组,对2组患者认知功能损害的潜在影响因素进行单因素分析,对有统计学意义的指标进行多元logistic回归分析,并依据Hcy水平进行脑梗死后认知功能障碍的相对危险度评价。结果:logistic回归分析显示,年龄、接受高等教育、糖尿病和Hcy水平均是脑梗死后认知功能障碍的影响因素（OR值分别为0.94、1.21、1.86、2.35）。认知功能障碍组患者血浆Hcy水平为（14.87±5.85）μmol/L,明显高于无认知障碍组的（12.78±5.68）μmol/L（P<0.01）;高Hcy血症患者脑梗死后认知功能障碍发生率高于非高Hcy血症患者（P<0.05）,相对危险度为1.92,95%CI为1.125~3.289。结论:Hcy水平是急性脑梗死后认知功能障碍的重要影响因素,高Hcy血症患者脑梗死后认知功能障碍的风险增高。     

Apelin-13通过AMPK通路抑制同型半胱氨酸诱导的内皮细胞损伤

目的 观察Apelin-13对同型半胱氨酸(Hcy)诱导的血管内皮细胞损伤的保护作用并探讨其可能的作用机制。方法采用10 mmol/L Hcy处理人脐静脉内皮细胞(HUVECs)24 h,诱导内皮细胞的损伤。采用不同浓度(0.1 μmol/L、1.0 μmol/L和10.0 μmol/L)的Apelin-13预处理1 h,再加入含Hcy的培养基中继续孵育24 h,观察细胞的损伤情况。采用MTT法测定细胞活力,比色法测定细胞培养液中乳酸脱氢酶(LDH)的活性。采用Western Blot检测HUVECs中磷酸化的腺苷酸活化蛋白激酶(AMPK)蛋白表达。结果与对照组比较,Hcy组细胞的存活率显著降低,细胞培养液中LDH活力显著性升高(均P＜0.05)。与Hcy组组比较,Apelin-13(1.0和10.0 μmol/L)预处理组细胞的存活率均显著升高,细胞培养液中LDH活力显著性降低(均P＜0.05)。Hcy组HUVECs细胞中p-AMPK蛋白的表达与对照组比较没有显著性差异(均P＞0.05)。与Hcy组比较,Apelin-13(1.0和10.0 μmol/L)预处理组HUVECs细胞中p-AMPK蛋白的表达显著性下调(均P<0.05)。AMPK抑制剂Compound C部分取消了Apelin-13的内皮细胞保护作用。结论Apelin-13抑制了同型半胱氨酸诱导的内皮细胞损伤,其机制与可能与上调AMPK的磷酸化有关。     

Enhanced platelet aggregation, high homocysteine level, and microvascular disease in diabetic muscle infarctions: implications for therapy

Muscle infaction is a rare complication in patients with diabetes mellitus, probably because of the rich vascular supply of this tissue. We describe a patient with type 1 diabetes who had infarction of the muscles in her right thigh. We report, for the first time, that the patient, in addition to an advanced microvascular disease in the muscle, had increased plasma total homocysteine levels and increased platelet aggregation. These pathologies might have a synergistic effect on the development of this rare complication and should be treated aggrssively to prevent further episodes.     

Functional and reactive hyperemia are unaltered by homocysteine in conscious dogs

Summary The purpose of this study was to test the hypothesis that L-homocysteine thiolactone (L-HCTL), through its reaction with adenosine to formS-adenosylhomocysteine, may modulate myocardial functional and reactive hyperemic responses. Reactive hyperemic responses to 10-sec occlusions or 400-msec diastolic occlusions of the circumflex coronary artery and functional hyperemic responses to ventricular extra-activations were studied in a chronic heart-blocked dog preparation during a control period and following L-HCTL (40 mg/kg). In two additional dogs multiple venous blood samples and left ventricular myocardial biopsies were obtained following L-HCTL to measure changes in plasma homocysteine and tissueS-adenosylhomocysteine. Despite a 75-fold increase in peak plasma homocysteine and a 26-fold increase in tissueS-adenosylhomocysteine, L-HCTL did not alter myocardial functional and reactive hyperemic responses.The rapid increase in myocardialS-adenosylhomocysteine confirmed cellular entry of homocysteine and its reaction with endogenous adenosine. The failure of L-HCTL to alter functional and reactive hyperemic responses suggests that either such treatment does not affect myocardial release of adenosine or that adenosine is not an important regulator of coronary flow.Supported in part by the National Institutes of Health Grants HL 18468 and AM 12828 and the Medical Research Service of the Veterans Administration. Dr. Sadick is a recipient of an Overseas Research Fellowship from the Australian National Heart Foundation. Parts of this work were presented at the 56th Scientific Sessions, American Heart Association, Anaheim, California, November, 1983.     

Significant association of deficiency of hemoglobin, iron and vitamin B12, high homocysteine level, and gastric parietal cell antibody positivity with atrophic glossitis

J Oral Pathol Med (2012) 41 : 500–504 Background: Atrophic glossitis (AG) is considered to be a marker of nutritional deficiency. In this study, we evaluated whether there was an intimate association of the deficiency of hemoglobin, iron, vitamin B12 or folic acid, high blood homocysteine level, and serum gastric parietal cell antibody (GPCA) positivity with AG. Methods: The blood hemoglobin, iron, vitamin B12, folic acid, and homocysteine concentrations and the serum GPCA level in 176 AG patients were measured and compared with the corresponding levels in 176 age‐ and sex‐matched healthy control subjects. Results: We found that 39 (22.2%), 47 (26.7%), 13 (7.4%), and 3 (1.7%) AG patients had deficiencies of Hb (men < 13 g/dl, women < 12 g/dl), iron (<60 μg/dl), vitamin B12 (<200 pg/ml), and folic acid (<4 ng/ml), respectively. Moreover, 38 (21.6%) AG patients had abnormally high blood homocysteine level, and 47 (26.7%) AG patients had serum GPCA positivity. AG patients had a significantly higher frequency of Hb, iron, or vitamin B12 deficiency, of abnormally elevated blood homocysteine level, or of serum GPCA positivity than healthy control subjects (all P‐values = 0.000). However, no significant difference in frequency of folic acid deficiency was found between AG patients and healthy control subjects. Conclusion: We conclude that there is a significant association of deficiency of hemoglobin, iron and vitamin B12, abnormally high blood homocysteine level, and serum GPCA positivity with AG.     

A magnetic nanoparticles-based method for DNA extraction from the saliva of stroke patients

C677T polymorphism in the methylenetetrahydrofolate reductase （MTHFR） gene is a risk factor for stroke, suggesting that widespread detection could help to prevent stroke. DNA from 70 stroke pa- tients and 70 healthy controls was extracted from saliva using a magnetic nanoparticles-based method and from blood using conventional methods. Real-time PCR results revealed that the C677T polymorphism was genotyped by PCR using DNA extracted from both saliva and blood samples. The genotype results were confirmed by gene sequencing, and results for saliva and blood samples were consistent. The mutation TT genotype frequency was significantly higher in the stroke group than in controls. Homocysteine levels were significantly higher than controls in both TT genotype groups. Therefore, this noninvasive magnetic nanoparticles-based method using saliva samples could be used to screen for the MTHFR C677T polymorphism in target populations.