Type II pneumocytes modulate surfactant production in response to cigarette smoke constituents: Restoration by vitamins A and E

This study was to evaluate the effects of cigarette smoke constituents upon type II pneumocyte surfactant production in vitro, and how vitamins A and E may alter the response. Freshly isolated type II pneumocytes from Sprague–Dawley rats were incubated 20 h in medium with fetal bovine serum that was or was not treated with cigarette smoke. The number of adherent cells was inversely related to the dose of smoke or benzo(a)pyrene. Despite the decreased number of treated cells, the total amount of surfactant per culture well was unchanged, whereas surfactant production per cell was significantly increased (P < 0.05). Vitamin A concentration was significantly (P < 0.05) lower in the smoke-treated serum compared with untreated serum. When vitamin A or E was added to the cigarette smoke-treated serum, cell adherence and surfactant production returned to control values. In conclusion, cigarette smoke constituents or benzo(a)pyrene alone decreased the number of adherent type II pneumocytes, but did not alter surfactant amounts because of an increased production of surfactant per cell. Type II pneumocytes seem to adjust surfactant production dependent upon the number of type II pneumocytes to produce it and vitamin A or E enhance cell attachment in the presence of the smoke toxins.     

Altered islet Beta-cell function before the onset of Type 1 (insulin-dependent) diabetes mellitus

Summary To define the glucose to insulin dose-response relationship before the onset of diabetes, we studied 22 nondiabetic co-twins of patients with Type 1 (insulin-dependent) diabetes mellitus and nine control subjects. All had intravenous glucose tests at 0.02, 0.1 and 0.5 g/kg and were followedup prospectively for at least 6 years. Seven twins developed diabetes a mean of 7 months later; the remaining 15 are now unlikely to develop diabetes. The seven pre-diabetic twins had higher fasting insulin levels than control subjects (4.2±2.0 vs 1.8±1.8 nmol/l; p<0.05); but lower glucose clearance (1.0±0.5 vs 1.9±0.7 %/min; p<0.05), first phase insulin response at 0.5 g/kg (21.1±23.2 vs 143±50 nmol/l; p<0.0001), and total insulin responses at 0.1 g/kg (p<0.05) and 0.5 g/kg (p<0.00005). Using a curve-fitting programme, the normal glucose to insulin relationship was lost in prediabetic twins who had lower coefficient of determination (R²) than control subjects (p<0.01). In contrast, 15 low-risk twins and their nine control subjects had similar fasting glucose and insulin levels, glucose clearance, R² and insulin secretory responses to different glucose loads. The positive predictive values of subnormal R² and subnormal first phase insulin response were 67 % and 58 % respectively. These observations demonstrate an altered glucose to insulin dose-response relationship and loss of maximum insulin secretory response to glucose before the onset of Type 1 diabetes.     

The Swedish childhood diabetes study — a multivariate analysis of risk determinants for diabetes in different age groups

Summary In a nationwide incident case-referent study stepwise univariate analysis has revealed several risk determinants for childhood diabetes mellitus. In a multivariate analysis we have determined the set of risk determinants that would independently predict childhood Type 1 (insulin-dependent) diabetes. Possible interactions between the risk determinants and differences in risk profiles with different ages at onset were also examined. Reported familial insulin-treated and non-insulin-treated diabetes were significant risk factors in all age groups, as was also a low frequency of milk intake. The frequency of infections and a high intake of foods rich in nitrosamine tended to interact (OR 11.8, p=0.053) indicating a synergistic effect. A Cox regression analysis revealed that stressful life events during the last year was the only variable that tended to affect the age at onset (p=0.055). This indicated that psychological stress may rather precipitate than induce Type 1 diabetes. A short breast-feeding duration (OR=3.81), and an increased body height (OR=3.82) contributed significantly to the predictive model in only the youngest age group (0–4 years). An increased frequency of infections in the year preceding onset (OR=2.15) and no vaccination against measles (OR=3.33) contributed significantly to the model only in the age group 5–9 years. Various nutrients had different impacts on the risk of developing Type 1 diabetes in different age groups. It is concluded that in the genetically susceptible child, risk factors which are associated with eating habits, frequency of infections, vaccination status, growth pattern and severe psychological stress affect the risk of developing diabetes independently of each other. The set of risk determinants varies with the age at onset. A high frequency of infections and a high frequency of nitrosamine-rich food intake seem to have a synergistic effect on the risk of developing diabetes in childhood.     

2型糖尿病患者载脂蛋白E基因多态性的研究

目的：探讨中国人2型糖尿病患者载脂蛋白E（apoE)基因多态性及其与血脂和载脂蛋白水平的关系。方法：采用聚合酶链反应－限制性酶切片段长度多态性法，分别对74例2型糖尿病患者及191例血脂、血糖正常且无糖尿病史者的apoE基因型、空腹血脂及载脂蛋白AI、AⅡ、B100、CⅡ、CⅢ及E进行全面分析。结果：2型糖尿病患者的血清甘油三酯（TG）、总胆固醇（TC），低密度脂蛋白胆固醇（LDLC），非高密度脂蛋白胆固醇（nHDLC),载脂蛋白B100、CⅡ、CⅢ、E水平及TG／HDLC比值较对照组显著升高（P＜0．01）；血清高密度脂蛋白胆固醇（HDLC），apoE/apoCⅢ比值显著降低（P＜0．05）。2型糖尿病组与对照组apoE基因频率分布无显著性差异（P＞0．05）。携带ε2等位基因组血清TG／HDLC比值较E3／3基因型显著降低；而携带ε4等位基因组血清apoAⅡ水平较E3／3基因型及携带ε2等位基因组显著升高（P＜0．001）。结论：2型糖尿病患者apoE基因多态性与血TG／HDLC及apoAⅡ有一定关联。     

Hyperglycaemia compensates for the defects in insulin-mediated glucose metabolism and in the activation of glycogen synthase in the skeletal muscle of patients with Type 2 (non-insulin-dependent) diabetes mellitus

Summary Insulin resistance and a defective insulin activation of the enzyme glycogen synthase in skeletal muscle during euglycaemia may have important pathophysiological implications in Type 2 (non-insulin-dependent) diabetes mellitus. Hyperglycaemia may serve to compensate for these defects in Type 2 diabetes by increasing glucose disposal through a mass action effect. In the present study, rates of whole-body glucose oxidation and glucose storage were measured during fasting hyperglycaemia and isoglycaemic insulin infusion (40 mU·m^–2min^–1, 3 h) in 12 patients with Type 2 diabetes. Eleven control subjects were studied during euglycaemia. Biopsies were taken from the vastus lateralis muscle. Fasting and insulin-stimulated glucose oxidation, glucose storage and muscle glycogen synthase activation were all fully compensated (normalized) during hyperglycaemia in the diabetic patients. The insulin-stimulated increase in muscle glycogen content was the same in the diabetic patients and in the control subjects. Besides hyperglycaemia, the diabetic patients had elevated muscle free glucose and glucose 6-phosphate concentrations. A positive correlation was demonstrated between intracellular free glucose concentration and muscle glycogen synthase fractional velocity insulin activation (0.1 mmol/l glucose 6-phosphate: r=0.65, p<0.02 and 0.0 mmol/l glucose 6-phosphate: r= 0.91, p<0.0001). In conclusion, this study indicates an important role for hyperglycaemia and elevated muscle free glucose and glucose 6-phosphate concentrations in compensating (normalizing) intracellular glucose metabolism and skeletal muscle glycogen synthase activation in Type 2 diabetes.     

慢性肾脏病患者肾组织蛋白酶B的表达及意义

目的 探讨慢性肾脏病患者肾组织蛋白酶B(cathepsin B，CB)的表达及其与肾组织纤维化的关系。方法 采用免疫组织化学SP法和计算机图像分析系统检测肾组织CB、IV型胶原的表达情况，并以体视学多能目镜测试系统对肾活检组织病理切 片进行形态计量，计算硬化肾小球比率及病变肾小管肾间质比率。结果 CB在近曲小管表达最高，在肾小球和肾小管其他部位表达较少。轻度纤维化组和中度纤维化组CB的表达明显低于无纤维化组。CB表达与Ⅳ型胶原表达、病变肾小管肾间质比率及硬化肾小球比率呈显著负相关。结论 CB主要在肾近曲小管表达，其表达成少是细胞外基质(extracellular matrtx，ECM)降解减少的原因之一，参与肾组织纤维化的发生机制。     

中枢和外周脑钠素(BNP)调节醛固酮分泌的不同作用

将BNP和AT-Ⅱ、ACTH AVP单独或BNP与这3种肽分别合并在大鼠icv或iv注入后观察血Ald浓度的变化。实验结果表明:①iv给予AVP(5μg/3ml·h~(-1))、ACTH(5μg/3ml·h~(-1))和AT-Ⅱ(5 v.g/3 ml·h(-1)),1h后均能增加血Ald的浓度。iv给予BNP(5μg/3ml·h(-1))能明显抑制AVP和ACTH的刺激作用,而不影响AT-Ⅱ的刺激作用。②icv给予BNP(2 Vg/10 pl NS)能降低血Aid浓度。icv给予AVP(2μg/10μl NS)能增加血Aid浓度,但ACTH(2μg/10μl NS)和AT-Ⅱ(2μg/10μl NS)无此种作用。但如脑室同时给予BNP(2μg/10μlNS)却可明显刺激Aid分泌。③icv注入BNP对外周注入的3种多肽的刺激作用无任何影响。从上述的实验结果可看出:脑内BNP可“反常”地增加AT-Ⅱ、ACTH和AVP对Ald分泌的刺激作用,与外周抑制AVP,ACTH的刺激作用不同。而脑内BNP不影响这3种多肽的外周刺激作用。结论是脑内BNP以其独特的方式调节Ald的分泌,控制水盐代谢。     

枳鳖胶囊抗大鼠肝纤维化形态学及肝组织Ⅲ型胶原mRNA表达的实验研究

目的:观察枳鳖胶囊抗肝纤维化形态学和Ⅲ型胶原mRNA表达的变化。方法:选择66只健康清洁级SD大鼠,雌雄各半,随机分为:正常对照组,模型组,秋水仙碱组,枳鳖胶囊大、中、小剂量组。以40%四氯化碳花生油皮下注射结合高脂饲料、酒水饮料复合因素诱导大鼠肝纤维化模型。造模结束后,除正常组不予处理外,其他组分别以蒸馏水,秋水仙碱混悬液,高、中、低浓度枳鳖胶囊溶液灌胃,疗程36d。疗程结束后,观察大鼠新鲜肝脏的表面情况、色泽、质地等大体形态,测定肝组织Ⅲ型胶原mRNA的表达,光镜观察肝组织HE染色和网状纤维染色的病理形态学改变。结果:模型组大鼠肝细胞损害、肝脏脂肪变性和胶原纤维增生的程度最显著,Ⅲ型胶原mRNA的表达最强。枳鳖胶囊组上述改变明显减轻,且可抑制Ⅲ型胶原mRNA的表达,疗效优于秋水仙碱组。结论:枳鳖胶囊可较好地保护肝细胞,并能阻止肝纤维化进程甚或逆转肝纤维化病理改变,抑制胶原基因表达,抑制胶原基因表达可能是其抗肝纤维化的作用机理之一。     

Comparison of the diagnostic criteria for diabetes mellitus, WHO-1985, ADA-1997 and WHO-1999 in the adult population of Asturias (Spain).

AIMS: To estimate the prevalence of diabetes mellitus with three diagnostic criteria (WHO-1985 and 1999 and ADA-1997), evaluate their concordance and analyse the sensitivity and specificity of the different screening strategies for diabetes. METHODS: A cross-sectional population study with two-step sampling. One thousand and 34 people were selected randomly. A 75-g oral glucose tolerance test (OGTT) was performed and venous blood samples were obtained fasting and at 2 h. RESULTS: The prevalence of known Type 2 diabetes mellitus (DM-2) is 4%[95% confidence interval (CI) 2.8, 5.1]. By WHO-1985 criteria the prevalence of unknown DM-2 is 5.9% (4.5, 7.4); by ADA-1997 criteria 3.5% (2.5, 4.6) and by WHO-1999 criteria 7.3% (5.8, 8.8). Diagnostic overlap and statistical concordance (coefficient K) are WHO-1985/ADA-1997 29.3%, K=0.42; WHO-1985/WHO-1999 80%, K=0.88; ADA-1997/WHO-1999 48%, K=0.63. If only fasting glucose was used (following ADA-1997), 36.3% of those with diabetes (2-h glucose > or =11.1 mmol/l) would be diagnosed. If OGTT was performed (i) in those with a fasting glucose between 6.1 mmol/l and 6.9 mmol/l (9.8% of the population) we would diagnose 66.6%, and (ii) in all those between 5.7 mmol/l and 6.9 mmol/l (18.9% of the population) 81.8% would be diagnosed. CONCLUSIONS: The ADA criteria decrease the prevalence of DM in the adult population of Asturias by 2.4% and concordance with the classical criteria (WHO-1985) was only 29.3%. Using fasting glucose only (ADA-1997) diagnoses 36.3% of those with diabetes. The recent recommendations of the WHO-1999 increases this to 66.6%. To improve the diagnostic strategy for diabetes and detect up to 81.8% of patients, we propose the use of OGTT for all those with a fasting glucose between 5.7 mmol/l and 6.9 mmol/l.