Reduced peripheral blood mitochondrial DNA content is not a risk factor for Type 2 diabetes.

AIMS: Mitochondrial depletion in pancreatic beta cells is known to reduce glucose stimulated insulin secretion. We aimed to determine whether the offspring of patients with early onset Type 2 diabetes had reduced peripheral blood mitochondrial content relative to control subjects and whether this could lead to a predisposition to type 2 diabetes in later life. METHODS: We measured the levels of mitochondria relative to a single copy genomic target by real time polymerase chain reaction in a series of peripheral blood samples taken from the offspring of Caucasian patients with Type 2 diabetes and matched controls. Measures of insulin sensitivity and beta cell function were also taken. RESULTS: In contrast with previous studies, mitochondrial DNA content was not decreased in the offspring of patients with Type 2 diabetes relative to matched controls in our cohort. Conversely, we noted a small proliferation in mitochondrial numbers in our case subjects. In agreement with these findings, no correlations with either insulin sensitivity or beta cell function were noted. CONCLUSIONS: Our results indicate that reduced mitochondrial DNA content in peripheral blood is not a risk factor for the development of Type 2 diabetes in the offspring of patients with early onset Type 2 diabetes.     

复方通络中药改善肥胖患者血管内皮细胞功能障碍研究

目的观察复方通络中药对单纯性肥胖患者血管内皮依赖性舒张功能障碍的干预效应，探讨其作用机制。方法应用高分辨血管超声检查选择血管内皮依赖性舒张功能障碍[以血流介导的肱动脉扩张率（FMD）表示]肥胖患者（65例），随机分为通络中药治疗组和对照组。治疗组32例，对照组33例。治疗组给予辛香疏络2号胶囊，3g／次，每日3次；对照组给予淀粉胶囊，3g／次，每日3次。共用药12周，分别测定用药前后FMD、肱动脉内径（D0），同时检测辛香疏络2号治疗前后患者血清总胆固醇（TC）、三酰甘油（TG）的变化。结果治疗后治疗组FMD较对照组明显增加（P〈0．01），TC、TG较治疗前及对照组明显下降（P〈0．01）。结论复方通络中药辛香疏络2号胶囊可明显改善肥胖患者血管内皮障碍，调节血脂可能是其改善血管内皮功能机制之一。     

Association of diabetes-related emotional distress with diabetes treatment in primary care patients with Type 2 diabetes.

AIMS: To characterize the determinants of diabetes-related emotional distress by treatment modality (diet only, oral medication only, or insulin). METHODS: A total of 815 primary care patients with Type 2 diabetes completed the Problem Areas in Diabetes (PAID) Scale and other questions. We linked survey data to a diabetes clinical research database and used linear regression models to assess the associations of treatment with PAID score. RESULTS: PAID scores were significantly higher among insulin-treated (24.6) compared with oral-treated (17.8, P < 0.001) or diet-treated patients (14.7, P < 0.001), but not different between oral- vs. diet-treated patients (P = 0.2). Group scores remained similar, but the statistical significance of their differences was reduced and ultimately eliminated after sequential adjustment for diabetes severity, HbA(1c), body mass index, regimen adherence, and self-blood-glucose monitoring. Insulin-treated patients reported significantly higher distress than oral- or diet-treated patients on 16 of 20 PAID items. 'Worrying about the future' and 'guilt/anxiety when ... off track with diabetes' were the top two serious problems (PAID >or= 5) in all treatment groups. Not accepting diabetes diagnosis was a top concern for oral- and diet-treated patients, and unclear management goals distressed diet-treated patients. CONCLUSIONS: Primary care patients treated with insulin reported higher diabetes-related emotional distress compared with oral- or diet-treated patients. Greater distress was largely explained by greater disease severity and self-care burdens. To improve diabetes-specific quality of life, clinicians should address patients' sense of worry and guilt, uncertain acceptance of diabetes diagnosis, and unclear treatment goals.     

M_2和β_1受体抗体与慢性肺源性心脏病关系的实验研究

目的用缺氧方法制备的肺源性心脏病(肺心病)大鼠为对象,研究肺心病中M2和β1受体抗体的含量及其与疾病的关系。方法选取健康雄性Wistar大鼠36只,随机分为3组:单纯缺氧组,缺氧加注射FeCl3组,健康对照组。SA-酶联免疫吸附测定(ELISA)法检测血清M2和β1受体抗体变化。最后处死大鼠观察心脏指标,并分析它与抗体滴度的相关性。结果血清中M2和β1受体抗体随缺氧时间延长而升高,滴度分别到第3周达高峰M2受体抗体为1∶80(单纯缺氧组)和1∶53(缺氧加注射FeCl3组),β1受体抗体为1∶60(单纯缺氧组)和1∶45(缺氧加注射FeCl3组),并且P/N值从第2周开始有阳性意义,到第3周同样达高峰M2和β1受体抗体分别为2.88(单纯缺氧组)、2.76(缺氧加注射FeCl3组)和3.25(单纯缺氧组)、3.99(缺氧加注射FeCl3组)。而肺心病大鼠心脏指标最终改变为R/(L+S)0.333±0.027(单纯缺氧组),0.348±0.033(缺氧加注射FeCl3组),R/BW×10-30.58±0.13(单纯缺氧组),0.60±0.15(缺氧加注射FeCl3组),(L+S)/BW×10-32.000±0.024(单纯缺氧组),2.081±0.037(缺氧加注射FeCl3组),并且抗体滴度与心脏改变呈正相关。结论M2和β1受体抗体阳性率及抗体滴度在大鼠肺心病模型中明显增高,表明肺心病的发生发展与M2和β1受体的自身抗体密切相关。     

MMP-2、TIMP-2、VEGF和bFGF在血管瘤增生及消退过程中的变化

目的 探讨基质金属蛋白酶-2（MMP-2）及其抑制剂（TIMP-2）、血管内皮生长因子（VEGF）和碱性成纤维细胞生长因子（bFGF）在血管瘤增生、消退过程中的变化。方法 采用免疫组织化学链霉亲和素-过氧化酶（SP）法，检测增生期血管瘤32例、消退期血管瘤10例、血管畸形17例及小儿正常皮肤10例标本中MMP-2、TIMP-2、VEGF及bFGF的表达。结果 MMP-2、VEGF及bFGF在增生期血管瘤中的表达明显高于消退期血管瘤、血管畸形和正常皮肤，其差异有统计学意义；TIMP-2在消退期血管瘤中的表达明显高于增生期血管瘤、血管畸形和正常皮肤，其差异有统计学意义。结论 MMP-2、VEGF及bFGF可能促进血管瘤血管生成，从而促进血管瘤增生，而TIMP-2可能促进血管瘤消退。     

天麻钩藤饮对脑缺血大鼠的神经保护机制研究

目的 观察天麻钩藤饮对脑缺血大鼠学习记忆能力,VEGF及其受体VEGFR-2/FLK-1的影响,探讨天麻钩藤饮的脑保护作用机制.方法 采用大鼠双侧颈动脉永久性结扎制备脑缺血模型,于术后次日开始给予天麻钩藤饮[5g/(kg·d)]灌胃,分别于2周及4周通过Morris水迷宫观察大鼠行为学的改变,免疫组化观察VEGF及FLK-1的改变.结果 模型组大鼠的潜伏期较假手术组明显延长,记忆能力明显下降.治疗组较模型组明显好转,4周较2周更为明显.2周模型组VEGF、FLK-1主要在神经元表达,较假手术组明显增多,4周表达下降;治疗组VEGF、FLK-1在神经元的表达较模型组明显增多,4周仍高表达.结论 该研究提示,天麻钩藤饮可能通过促进VEGF和特异性受体FLK-1的表达,启动神经元保护机制,发挥脑保护作用,改善脑缺血后大鼠的行为学表现.     

A -243A-->G polymorphism upstream of the gene encoding GAD65 associates with lower levels of body mass index and glycaemia in a population-based sample of 5857 middle-aged White subjects.

AIMS: The glutamate decarboxylase gene (GAD2) encodes GAD65, an enzyme catalysing the production of the gamma-aminobutyric acid (GABA) which interacts with neuropeptide Y to stimulate food intake. It has been suggested that in pancreatic islets, GABA serves as a functional regulator of pancreatic hormone release. Conflicting results have been reported concerning the potential impact of GAD2 variation on estimates of energy metabolism. The aim of this study was to elucidate potential associations between the GAD2-243A-->G polymorphism and levels of body mass index (BMI) and estimates of glycaemia. METHODS: Using high-throughput chip-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, the GAD2-243A-->G (rs2236418) polymorphism was genotyped in a population-based sample (Inter99) of 5857 middle-aged, unrelated Danish White subjects. RESULTS: The G-allele was associated with modestly lower BMI (P = 0.01). In a case-control study of obesity, the G-allele frequency in 2582 participants with BMI < 25 kg/m2 was 19.5% (18.4-20.6) compared with 17.1% (15.5-18.8) in 968 participants having BMI > or = 30 kg/m2 (P = 0.03), odds ratio 0.9 (0.7-1.0). Of the 5857 subjects, GG carriers had lower fasting plasma glucose levels (mmol/l) [AA (n = 3859) 5.6 +/- 0.8; AG (n = 1792) 5.5 +/- 0.8; GG (n = 206) 5.5 +/- 0.8, P = 0.008] and lower 30-min oral glucose tolerance test (OGTT)-related plasma glucose levels (AA 8.7 +/- 1.9; AG 8.6 +/- 1.9; GG 8.6 +/- 2.0, P = 0.04), adjusted for sex, age and BMI. Analysing subjects who were both normoglycaemic and glucose tolerant (n = 4431) GG carriers still had lower fasting plasma glucose concentrations: AA (n = 2895) 5.3 +/- 0.4; AG (n = 1383) 5.3 +/- 0.4; GG (n = 153) 5.2 +/- 0.4 (P = 9.10(-5)). CONCLUSION: The present study suggests that the GAD2-243A-->G polymorphism in a population of middle-aged White people associates with a modest reduction in BMI and fasting and OGTT-related plasma glucose levels.     

Addition of Transdermal or Inhaled Long-Acting β 2-Agonists in Adult Asthmatic Patients Treated with Inhaled Corticosteroids: Switchover Study from Tulobuterol Patch to Salmeterol Dry Powder Inhaler

Sixty-four patients with persistent asthma receiving 200 to 800 μ g of fluticasone propionate daily were enrolled in this switchover study. The patients applied a tulobuterol patch 2 mg every 24 hours for 4 weeks followed by inhalation of salmeterol 100 μ g bid for 4 weeks. The mean values for morning and evening peak expiratory flow improved significantly compared with baseline during the 4 weeks of tulobuterol patch treatment. Further improvement was seen on switching to salmeterol treatment, which was significant even in the first week, and continued until the final week of the study. Use of salmeterol alone resulted in a significant increase in the percentage of forced expiratory volume in 1 second %FEV1 from baseline, with 51% of patients feeling that the treatment was effective (vs. 37% on tulobuterol). These data suggest that salmeterol can achieve better control in asthmatic patients after switching from using tulobuterol patches.