高糖通过活化半胱氨酸天冬氨酸蛋白酶3途径诱导人腹膜间皮细胞凋亡

目的 探讨高糖损伤人腹膜间皮细胞(HPMC)的机制。方法 (1)分离培养HPMC,以细胞形态、免疫细胞化学染色作细胞鉴定;(2)第2代HPMC分别经含1.5%、2.5%、4.25%葡萄糖的M199培养基培养48h后(以正常M199培养基和含4.25%甘露醇的M199培养基为对照),检测HPMC caspase-3活性和HPMC凋亡情况;(3)分别用25μmol/L、50μmol/L、和100μmol/LZ-VAD.fmk和4.25%葡萄糖共同刺激体外培养的HPMC(以DMSO和4.25%葡萄糖为对照),流式细胞仪观察HPMC凋亡情况,同时检测50μmol/L Z-VAD.fmk组和葡萄糖对照组caspase-3活性。结果 (1)HPMC caspase-3活性和凋亡率与葡萄糖浓度呈正相关(r分别为0.9506和0.9868,P<0.01),且HPMC caspase-3活性与凋亡率呈正相关(r=0.9860,P<0.01)。与M199对照组相比,2.5%葡萄糖组和4.25%葡萄糖组HPMC caspase-3活性和凋亡率显著增加(P<0.05),而1.5%葡萄糖组及4.25%甘露醇组HPMC caspase-3活性和凋亡率无显著差异(P>0.05)。(2)4.25%葡萄糖组caspase-3活性显著高于4.25%甘露醇组(P<0.05),但4.25%甘露醇组caspase-3活性与对照组相比无显著差异(P>0.05)。(3)与对照组相比,Z-VAD,fmk组HPMC凋亡率(P<0.05)和caspase-3活性(P<0.05)显著下降,且HPMC凋亡率与Z-VAD.fmk呈负相关(r=-0.8836,P<0.01)。结论 (1)高糖能以     

青中年人群微量白蛋白尿患病率与心血管疾病危险因素的关系

目的　探讨微量白蛋白尿患病率与心血管疾病危险因素的关系。方法　选择 775例 (男 32 6例 ,女 4 4 9例 )年龄 2 0～ 5 0岁的社区人群 ,测定其体重指数 (BMI)、血压、空腹血糖、血脂谱 ;收集晨尿检测尿白蛋白、尿肌酐浓度 ,并计算尿白蛋白 /尿肌酐的比率。根据有无高血糖、高血压或高三酰甘油 /低高密度脂蛋白胆固醇 (高TG/低HDL C)血症分为 4组 ,即正常组 (A组 )、1种代谢紊乱组 (B组 )、2种代谢紊乱组 (C组 )及代谢综合征组 (D组 ) ,评价微量白蛋白尿与代谢紊乱的关系。结果　①糖尿病患者微量白蛋白尿的患病率为 2 2 .2 % ,显著高于正常血糖者 (5 .2 % ,P =0 .0 0 2 ) ;高TG/低HDL C血症者微量白蛋白尿的患病率为 8.3% ,显著高于正常血脂者 (4.0 % ,P =0 .0 12 ) ;高血压患者与正常血压者的差异无显著性。②随代谢紊乱加重 ,尿白蛋白浓度显著升高 (协方差分析 ,P <0 .0 1) ,微量白蛋白尿患病率升高 (趋势分析 ,P =0 .0 0 3)。③ 4组间尿肌酐浓度、尿白蛋白 /尿肌酐的差异无显著性。结论　①糖尿病、高TG/低HDL血症人群的微量白蛋白尿的发病率显著升高。②随代谢紊乱加重 ,微量白蛋白尿患病率亦升高     

Fecal stream is essential for adaptive induction of glucose-coupled sodium transport in the remnant ileum after total proctocolectomy

Our previous studies demonstrated that sodium glucose cotransporter 1 (SGLT-1) was induced in the remnant ileum of total colectomized rats via the action of factors other than hyperaldosteronism. The aim of the present study was to clarify whether fecal stream is required for the enhancement of SGLT-1-mediated sodium transport. Twenty-seven pairs of ileal tissues were obtained from the proximal and distal side, respectively, of loop ileostomy after total proctocolectomy. Mucosae were mounted in an Ussing chamber to evaluate glucose-coupled sodium transport. Levels of SGLT-1 mRNA in proximal and distal mucosae were compared by Northern blotting. Villous height and crypt depth were measured to test for correlations between mucosal structure and SGLT-1-mediated sodium transport or mRNA expression levels. Both glucose-coupled sodium transport and expression of SGLT-1 mRNA were significantly lower in distal mucosae relative to proximal mucosae. In distal mucosae, villous height, but not crypt depth, was significantly lower than in proximal mucosae, demonstrating a positive correlation between villous height and SGLT-1 function and expression. Comparative studies of proximal and distal mucosae demonstrated that in addition to hormonal changes, fecal stream is required for full induction of the sodium transport system (which includes SGLT-1-mediated transport) in the remnant ileum following total proctocolectomy. Presented in part at the Forty-Sixth Annual Meeting of The Society for Surgery of the Alimentary Tract, Chicago, Illinois, May 14–19, 2005 (poster presentation). This work was supported by Grants-in-Aid for Scientific Research 10557118 and 14657295 from the Ministry of Education, Science and Culture of Japan to K. Fukushima, and by Kanae Foundation to K. Fukushima.     

高血糖对急性颅脑伤预后的影响

对ＩＣＵ收治的６１例急性闭合性颅脑伤患者入院２４ｈ血糖水平与急性期格拉斯哥昏迷评分、颅脑伤不同类型及预后进行分析。结果提示：格拉斯哥昏迷评分与血糖水平经回归分析呈显著负相关（ｒ＝－０．９６４，Ｐ＜０．０１）；不同类型颅脑伤患者以脑挫裂伤组血糖最高。高血糖组患者病死率明显高于非高血糖组，死亡组患者血糖明显高于恢复不良组及恢复良好组。作者认为，血糖测定有助于了解颅脑伤的严重程度，同时可以估计患者的预后，在颅脑伤的救治过程中加强血糖监测是必要的。     

Pathogenesis of progressive muscular dystrophy: studies on free radical metabolism in an animal model

Evidence to suggest the presence of abnormal metabolism of oxygen free radicals in progressive muscular dystrophy is presented using an animal model. In the superficial pectoral muscles of dystrophic chickens, enzyme activities regulating the metabolism of oxygen free radicals, i.e., catalase, superoxide dismutases and glutathione peroxidase, were significantly elevated within 1 week of hatching. Activities of related enzymes, i.e., glutathione reductase, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase were also elevated. In contrast, the specific activity of phosphofructokinase, the rate-limiting enzyme of the glycolytic pathway, was normal during the first 4-week period. These results suggest that there is an increased turnover of oxygen free radicals in the dystrophic muscle. This concept appears important in a further investigation of the pathogenesis and treatment of progressive muscular dystrophies.     

Scopolamine abolishes cerebral blood flow response to somatosensory stimulation in anesthetized cats: PET study

The effect of the cholinergic blocker, scopolamine on the cerebral blood flow (CBF) response to vibrotactile stimulation of a fore paw was studied using high-resolution positron emission tomography and H₂¹⁵O in 5 pentobarbital-anesthetized cats. Before scopolamine injection, the CBF response to the stimulation was found in the contralateral somatosensory cortex (mean ratio (contralateral/ipsilateral) control: stimulated1.02 ± 0.02: 1.17 ± 0.05; P < 0.01). After intravenous injection of scopolamine (0.35 mg/kg), the CBF response was abolished. However, the cerebral metabolic rate of glucose (CMRGlu) response to the same stimulation was unchanged after scopolamine injection in the same cats. We concluded that scopolamine abolishes the CBF response but not neuronal response to stimulation. We suggest that cholinergic mechanisms may play an important role for mediating CBF coupling to neuronal activity during physiological stimulation.     

Relationship between maternal glycaemia and birth weight in glucose-tolerant women from different ethnic groups in New Zealand.

AIM: The aim of this study was to compare the population attributable fraction(PAF) for a large baby (> or =4 kg) due to glycaemia, weight and smoking in glucose-tolerant women from different ethnic groups. METHODS: A retrospective review of screening for gestational diabetes (GDM)and associated birth weight was undertaken in New Zealand European (n= 529), Maori (n= 540) and Pacific (n= 916) women. The proportion with a large baby was compared by 1-h post 50-g glucose challenge test tertile and maternal weight tertile. RESULTS: Large babies were more common from Pacific and European than Maori women (24.3%, 18.8%, 8.9%, respectively; P<0.001). Birth weight increased significantly with increasing glucose among Pacific women (P<0.001) even after adjusting for maternal weight and other confounders. The risk of having a large baby was 2.56 (1.82-3.60)-fold greater in women in the highest maternal weight tertile (> or =84 kg), with a significantly greater PAF in Pacific women(27.2%, 12.9%, 16.4%, respectively; P<0.001). The odds ratio (OR) of having a large baby increased with even mildly elevated maternal 1-h glucose concentrations [OR for 5.6-6.2 mmol/l: 1.54 (1.11-2.14); for > or =6.3 mmol/l: 2.06 (1.50-2.82)], with no ethnic differences in PAF (11.1-11.8%, 16.7-18.7%, respectively). Smoking and being Maori were associated with smaller babies. CONCLUSIONS: Increased maternal weight and glycaemia are associated with a greater proportion of large babies among glucose-tolerant women. Growth of Pacific babies may be more sensitive to a higher maternal glucose when the mother is obese.     

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.     

琼脂糖凝胶电泳法测定糖化血红蛋白及其临床应用

目的　采用琼脂糖凝胶电泳的方法测定糖化血红蛋白 (Hb Alc) ,了解 Hb Alc与空腹血糖的关系。方法　取正常人及糖尿病人 EDTA- K2抗凝全血 2 32例 ,制成血红蛋白溶液 ,使用法国 sebia公司 sebia HYDRASYS电泳仪及光密度计扫描仪 ,用琼脂糖凝胶进行电泳分离和光密度计扫描定量测定 Hb Alc;在全自动生化分析仪上用己糖激酶法测定空腹血糖。结果　对照组的 Hb Alc平均值 (% )为 x± s=5 .4 1± 0 .94 ,血糖的平均值 (mmol/ L )为 x± s=4 .92± 0 .87;糖尿病人的 Hb Alc平均值 (% )为 x± s=11.0 6± 4 .3,血糖的平均值 (mmol/ L )为 x± s=10 .86± 3.0 4 ,P<0 .0 1,血糖值与Hb Alc值有显著相关性 ,r=0 .985 ,回归方程 Y=1.10 15 x 1.815。结论　该方法标本用量少 ,分辨率高 ,重复性好 ,结果不受温度及胎儿血红蛋白的影响 ,Hb Alc可作为糖尿病控制的指标