内脂素、抵抗素在妊娠期糖尿病发病中的作用

目的探讨新近发现的两种脂肪细胞因子——内脂素和抵抗素,与胰岛素抵抗的关系及其在妊娠期糖尿病(GDM)发病中的作用。方法采用病例对照的研究方法,通过检测40例GDM孕妇和40例正常孕妇的血清内脂素(Visfa-tin)、抵抗素(Resistin)空腹血糖(FPG)和空腹胰岛素(FINS)水平,计算HOMA稳态模型胰岛素抵抗指数(IRI),比较两组胰岛素抵抗程度的差异,并进一步分析内脂素、抵抗素与胰岛素抵抗之间的关系及其在GDM发生过程中所起的作用。结果 (1)GDM组的血清内脂素、抵抗素、空腹血糖(FPG)、空腹胰岛素(FINS)和胰岛素抵抗指数(IRI)均明显高于对照组(P<0.01)。(2)相关分析表明:GDM孕妇的血清内脂素、抵抗素均与胰岛素抵抗指数(IRI)呈显著正相关(r=0.568,0.618,P=0.000),而内脂素与抵抗素之间亦呈密切正相关(r=0.919,P=0.000)。结论 (1)GDM孕妇的血清内脂素、抵抗素水平较正常孕妇明显增高。(2)内脂素、抵抗素均与胰岛素抵抗呈正相关。(3)血清内脂素、抵抗素水平增高以及二者对胰岛素敏感性调节所产生的综合效应是诱导妊娠期糖尿病发生或促进其发展的重要因素。     

硫化氢抑制小鼠胰岛素抵抗3T3-L1脂肪细胞系抵抗素的分泌

目的观察硫化氢(H2S)是否通过AMPK信号通路影响小鼠胰岛素抵抗3 T3-L1脂肪细胞系抵抗素的分泌。方法将细胞分为对照组、胰岛素抵抗3T3-L1组和50μmol/L Na HS组,利用ELISA法检测抵抗素(resistin)的分泌,Western blot检测AMP激活的蛋白激酶(AMPK)及乙酰辅酶A羧化酶(ACC)磷酸化蛋白的表达,实时荧光定量PCR(RT-PCR)检测resistin及AMPK mRNA表达。结果与对照组比较,给予Na HS后抵抗素分泌明显降低(P0.05)。正常和胰岛素抵抗细胞中AMPK和ACC磷酸化蛋白表达显著增加(P0.05)。AMPK通路特异性阻断剂compound C可减弱Na HS对AMPK及ACC蛋白磷酸化的作用,且降低正常和胰岛素抵抗细胞抵抗素的分泌。结论 H2S可能通过激活AMPK通路来抑制小鼠正常和胰岛素抵抗3 T3-L1脂肪细胞的抵抗素分泌。     

2型糖尿病患者血清抵抗素的检测及其与胰岛素抵抗的关系

目的 探讨检测血清抵抗素水平用于2型糖尿病诊断的意义,并分析其与胰岛素抵抗的关系. 方法 随机收集2型糖尿病患者117例、健康对照组109例,测定其空腹血糖、空腹胰岛素和抵抗素水平.比较上述指标在糖尿病患者和健康对照人群之间的差异.分析抵抗素用于糖尿病诊断的灵敏度、特异度、正确率和ROC曲线下面积.应用Pearson直线相关分析计算抵抗素与胰岛素抵抗指数的相关性. 结果 2型糖尿病患者的血清抵抗素、空腹血糖、空腹胰岛素及胰岛素抵抗指数均显著高于健康对照组(P<0.01).抵抗素用于糖尿病诊断的灵敏度为70.09%、特异度为64.22%、正确率为67.30%、ROC曲线下面积为0.695,诊断试验的准确度为中等.糖尿病患者的血清抵抗素水平与其胰岛素抵抗指数呈显著正相关(r=0.803,P<0.01). 结论 2型糖尿病的发生可能与抵抗素水平增高有关.检测血清抵抗素可用于糖尿病的辅助诊断,并可作为评价胰岛素抵抗程度的一种新的敏感指标.     

丝胶对Ⅱ型糖尿病大鼠肝胰岛素受体和胰岛素受体底物-2的调控作用

目的:研究丝胶对Ⅱ型糖尿病大鼠肝细胞胰岛素受体(IR)及胰岛素受体底物-2 (IRS-2)表达的影响.方法:SD大鼠随机分为5组,分别为正常对照组、糖尿病模型组、丝胶治疗组、阳性对照组、丝胶预防组.采用链脲佐菌素连续腹腔注射法制作Ⅱ型糖尿病大鼠模型.丝胶治疗组大鼠给予丝胶(2.4g·kg-1·d-1)灌胃35 d,阳性对照组大鼠给予二甲双胍(55.33 mg·kg-1·d-1)灌胃35 d,丝胶预防组大鼠于2％链脲佐菌素(25 mg/kg)连续腹腔注射之前给予丝胶(2.4g·kg-1·d-1)灌胃35d.采用葡萄糖氧化酶法检测各组大鼠的空腹血糖;SP免疫组织化学显色、蛋白免疫印迹和RT-PCR检测肝细胞中IR和IRS2的表达.结果:丝胶可明显上调糖尿病大鼠肝胰岛素受体和胰岛素受体底物-2mRNA表达,显著增加IR和IRS-2蛋白的表达.结论:丝胶可通过上调糖尿病肝IR和IRS-2的表达,改善胰岛素抵抗,起到降低血糖的作用.     

脂肪细胞在肝细胞胰岛素耐受过程中的作用

目的研究脂肪细胞在不同分化阶段对肝细胞胰岛素抵抗的影响。方法体外诱导3T3-L1脂肪前体细胞分化,细胞内脂滴增加,逐步分化成脂肪细胞。采用不同分化阶段脂肪细胞(未分化0d、中期分化4d、接近完全分化8d)与原代肝细胞共培养。Western印迹法检测共培养后肝细胞内胰岛素信号通路的反应性;葡萄糖同位素标记方法检测肝细胞糖原合成能力。结果以未共培养的肝细胞为对照组,共培养后肝细胞内胰岛素受体底物-2酪氨酸磷酸化(Tyr612)(pIRS-2)水平及Akt磷酸化(Ser473)(pAkt)水平均显著下调;肝糖原合成能力明显降低;与较成熟脂肪细胞共培养后,肝细胞pIRS-2及pAkt水平与其他分化阶段组共培养比较下调明显,肝糖原合成能力随着脂肪细胞的成熟而明显降低。结论脂肪细胞可能诱导肝细胞发生胰岛素抵抗,肝细胞胰岛素信号通路的阻滞程度与脂肪细胞的分化程度呈正相关。     

芥子碱硫氰酸盐抑制IR小鼠血脂血糖升高、动脉粥样硬化及肝细胞脂肪变性

目的:探究芥子碱硫氰酸盐(sinapine thiocyanate,ST)抑制胰岛素抵抗(insulin resistance,IR)小鼠血脂血糖升高、动脉粥样硬化及肝细胞脂肪变性的机制。方法:Apo E~(-/-)雄性小鼠60只随机分成对照组、生理盐水组、罗格列酮组和ST低、中、高剂量治疗组,每组10只。除对照组常规饲料喂养外,其余各组以高脂饲料饲养12周,ST低、中、高剂量组同时给予ST(10、30和90 mg·kg~(-1)·d~(-1))灌胃,罗格列酮组给予罗格列酮(1.33 mg·kg~(-1)·d~(-1))灌胃。最后3周,除对照组腹腔注射生理盐水外,其余各组腹腔注射地塞米松(0.8 mg·kg~(-1)·d~(-1))诱导IR。每周断尾采血检测空腹血糖水平,第12周末禁食12 h后处死动物取样,检测空腹胰岛素、肿瘤坏死因子α(TNF-α)、甘油三酯、总胆固醇及肝脂质等水平;将肝组织和主动脉固定包埋切片,HE染色。Western blot测定肝脂质代谢与骨骼肌MAPK信号通路相关蛋白表达。结果:ST呈剂量依赖性降低血脂、血糖及TNF-α等代谢相关指标的水平(P0.05),延缓肝细胞脂肪变性和动脉粥样硬化;并呈剂量依赖性调控肝脂质代谢信号通路(HMGR和SREBP-2等)及MAPK信号通路(ERK和p38等)蛋白表达(P0.05)。结论:ST抑制IR模型小鼠血脂血糖升高、动脉粥样硬化及肝细胞脂肪变性的机制可能与调控肝脂质代谢和骨骼肌MAPK信号通路相关蛋白表达有关。     

消退素D1改善2型糖尿病小鼠胰岛素抵抗

正胰岛素抵抗和慢性炎性反应密切相关。控制炎性反应的发生与发展有助于改善胰岛素抵抗。近期发现ω-3多不饱和脂肪酸的衍生物消退素D1(resolvin D1,RVD1)是一类新型的抗炎介质。其对胰岛素抵抗是否有改善作用仍不清楚,本研究探讨RVD1对2型糖尿病(T2DM)小鼠胰岛素抵抗的作用及其机制。1材料与方法1.1材料:SPF级6周龄C57BL/6雄性小鼠30只[北京维     

2型糖尿病合并高血压患者抵抗素与动脉粥样硬化的相关性研究

为探讨2型糖尿病合并高血压患者抵抗素与动脉粥样硬化(AS)的相关性,用彩色多普勒超声技术观察2型糖尿病(A组)29例患者,2型糖尿病合并高血压(B组)23例患者及20名对照组的颈动脉内中膜厚度(IMT)及斑块的变化;应用ELISA测定血浆抵抗素水平。结果表明:A组和B组抵抗素水平较对照组显著升高(P<0.01),且B组抵抗素较A组显著升高(P<0.05);抵抗素与IMT、SBP、FBG、HOMA-IR显著正相关,与FINS显著负相关;IMT与抵抗素、年龄、BMI、SBP、FBG、FINS、HbA1c、HOMA-IR显著正相关。本文提示抵抗素参与胰岛素抵抗(IR),在AS发生及发展中起着重要作用。     

2型糖尿病患者血浆抵抗素水平的变化及临床意义

2型糖尿病是常见的慢性病之一，它以靶组织对胰岛素抵抗及高血糖为主要特征，与肥胖具有高度相关性。抵抗素（Resistin）是2001年初Steppan等在小鼠脂肪组织中发现的一种新型蛋白质激素，动物实验表明抵抗索能影响糖代谢，具有对抗胰岛素作用，可能是肥胖导致胰岛素抵抗或糖尿病的发病机理之一。为此我们检测了57例2型糖尿病患者血浆抵抗素水平，并与40例体检健康者进行比较，以观察糖尿病患者血浆抵抗素水平的变化，并探讨其在2型糖尿病发病机理中的作用，现报告如下。     

抵抗素与胰岛素抵抗

抵抗素是最近发现的一种主要由脂肪细胞分泌的激素 ,因有对抗胰岛素的作用而得名。它在肥胖和胰岛素抵抗时表达明显增加 ,所以 ,有学者认为抵抗素是联系肥胖和胰岛素抵抗的中介。但也有实验结果不支持这些观点。抵抗素的表达受胰岛素增敏剂、营养状态及抵抗素拮抗剂等调节。     

Secular change in menarche in women in Madrid

The age at menarche was estimated by recollection in 1617 women between the ages of 18 and 60 in Madrid and a nearby suburb, Pinto. The population of Pinto is working-class and the Madrid group, taken from residential neighbourhoods , belongs to the upper middle class. In both groups we found a diminution in average age at menarche, from 14.04 to 13.02 years in Madrid and from 14.55 to 13.16 years from about 1935 to about 1965 in Pinto. These changes have been more intense in the group which is less well-off economically, where living conditions have varied much more drastically.     

Intestinal helminthiasis in school children in Haiti in 2002

A survey on intestinal helminths in school children was conducted in Haiti in 2002. This first nationwide study involving the entire country was stratified by department according to urban and rural zones using the cluster method. Focusing on elementary school children (n=5792; age range 3 to 20 years), it involved 26 urban and 49 rural schools randomly selected. Stools were preserved in formalin and examined by the Ritchie technique. Thirty-four per cent of stools (1981/5792) tested positive for intestinal helminths with the following parasites identified: Ascaris lumbricoides (27.3%), Trichuris trichiura (7.3%), Necator americanus (3.8%), Hymenolepsis nana (2%), Taenia sp. (0.3%) and Strongyloides stercoralis (0.2%). The helminth prevalence was higher in rural (38.4%) compared to urban areas (30%). There was no significant difference in prevalence by sex and age. The importance of geohelminths changed from one department to another with the highest prevalence found in the Southern department of Grande Anse (73.7%) and the lowest prevalence in the Center department (20.6%). Five out of the country's nine departments had a similar prevalence varying from 25.5% to 28.2%. Intestinal helminthic polyparasitism was observed in a percentage of infested school children comprise between 3.4% and 28.6% according in relation to the geographical area. A program to fight against geohelminths in school children should be initiated as a public health priority. Albendazole is the drug of choice. Frequency of drug distribution should be based on the prevalence of geohelminths in each department.     

Experience in adult population in dengue outbreak in Delhi

A dengue outbreak has recently hit the Indian capital. We studied the clinical profile of adult patients. Five hundred and sixty patients of dengue infection were admitted in a specially created ward according to the criteria laid down by WHO. Haematemesis (28.28%), epistaxis (26.78%) and malena (14.28%) were some of the common presentations. Similarly lymphadenopathy, especially cervical (30.89%), palatal rashes (26.96%) and hepatomegaly (23.75%) were the most commonly encountered findings on physical examination. Most of the cases were of dengue fever with haemorrhage and only 2.5% cases were classified under dengue haemorrhagic fever or dengue shock syndrome. The average hospital stay was 3.4 days but only 9.8 hours in the eleven patients who died, suggesting their late arrival in preterminal situation giving little time for resuscitation. Thrombocytopenia was not a feature and only 12.85% patients had platelet count less than 70,000/cmm. Most of the patients who were admitted with thrombocytopenia, showed normalization in their platelet counts in next few days. Serological examination demonstrated evidence of recent dengue infection in 41.17% patients. Few patients required blood or platelet concentrate transfusion. Eleven patients died, three due to DIC, one of intracranial haemorrhage and seven due to massive gastric haemorrhage. Rest of the patients recovered completely. Thus we can conclude that recent outbreak in Delhi was of dengue fever with haemorrhage and mortality was very low in patients who came early to the hospital.     

Changes in the hypothalamic nuclei in in experimental allergy

Summary In rabbits subjected to prolonged sensitization and in which the Arthus phenomenon was induced there was a marked reaction of the hypothalamic nuclei. Staining by Gomori's method indicated a cellular swelling, loss of granules, and protoplasmic vacuolization in the supraoptic nucleus. There was a considerable increase in the size of the cross-sectional area of the cells. The same effects were much less well shown in the paraventricular nucleus. These results show that marked signs of increased neurosecretion developed in the animals at the height of the Arthus phenomenon.(Presented by Active Member AMN SSSR V. V. Parin) Translated from Byulleten Éksperimental'noi biologii i Meditsiny, Vol. 55, No. 4, pp. 110–113, April, 1963.     

Development in in vitro toxicology

There are three principal pressures driving the development of in vitro toxicology: (1) the need for more efficient testing systems to cope with the large number of xenobiotics currently being developed; (2) public pressure to reduce animal experimentation; and (3) a need for a better understanding of the mechanisms of toxicity. Within this, in vitro toxicology is focused on local, systemic, and target-organ toxicity. It is becoming increasingly apparent that a step or decision-tree approach using input of a variety of experimental data (physicochemical properties, biokinetics, cytotoxicity) provides the most efficient system for predicting toxicity. Examples of the use of in vitro toxicity systems for prediction of systemic toxicity and target-organ (liver) toxicity are presented.Originally presented at ECCP 93.