瘦素及硬脂酰CoA去饱和酶-1在高脂饮食大鼠非酒精性脂肪肝发病中的作用

目的:研究瘦素及SCD-1在高脂饮食引起非酒精性脂肪肝形成及其药物治疗中的作用．方法:42只SD大鼠分成正常组、高脂组和干预组(自高脂饮食喂养8 wk起用罗格列酮进行干预16 wk)．酶联免疫法测定血清瘦素,RT-PCR实时荧光分析大鼠肝 SCD-1 mRNA与β-actin mRNA的比值．结果:肝组织HE染色显示高脂组大鼠肝脏内有弥漫性肝细胞脂肪变性,8 wk达到脂肪肝诊断标准．8,24 wk高脂组大鼠血清瘦素水平升高,与正常组相比有显著性差异(8 wk:5．29±1．83 μg／L vs 3．06±1．35 μg/L, P<0．05;24 wk:7．89±3．01 μg/L vs 3．09±1．52 μg/L, P<0．05);肝SCD-1 mRNA与β-actin mRNA的比值明显下降(8 wk:0．37±0．25 vs 0．82±0．34,P<0．05)．干预组与高脂组相比,血清瘦素水平下降(5．95±3．31 μg/L vs 7．89±3．01 g／L,P>0．05);肝SCD-1 mRNA表达明显增强(SCD-1/β-actin:1．02±0．11 vs 0．52±0．22,P<0．01)．结论:长期高脂饮食可导致血清瘦素水平升高,其通过下调肝SCD-1表达促进非酒精性脂肪肝的形成．罗格列酮可降低血清瘦素水平,上调肝SCD-1的表达,减轻因高脂饮食引起的非酒精性肝脂肪变．     

贞清方对2型糖尿病并发非酒精性脂肪肝大鼠LXRα表达的影响

目的:探讨贞清方对2型糖尿病非酒精性脂肪肝的治疗作用及可能机制.方法:高脂高糖饮食结合小剂量链脲佐菌素(STZ)腹腔注射建立2型糖尿病并发非酒精性脂肪肝大鼠模型.将成模大鼠随机分为模型组、贞清方治疗组和女贞子治疗组( n= 8),并设立正常对照组( n = 10),灌胃治疗8 wk.比较喂养4、8和16 wk时各组大鼠空腹血糖(FBG)、血清甘油三酯(TG)、总胆固醇(TC)、胰岛素(FINs)和胰岛素敏感指数(ISI)的变化.并于喂养16 wk时观察各组大鼠肝脏指数、TG含量和血清丙氨酸转氨酶(ALT)的水平以及病理变化.用PCR法观察大鼠肝X受体(LXRα)及其下游固醇调节元件结合蛋白-1c(SREBP-1c) mRNA的表达,免疫组织化学法观察肝脏LXRα蛋白的表达.结果:灌胃干预8 wk后,与正常组相比,模型组大鼠FBG、血清TG、肝脏指数及肝脏TG含量明显升高(均P<0.01),胰岛素敏感性明显降低( P<0.01),肝脏脂肪变明显加重,肝脏LXRα mRNA、SREBP-1c mRNA和LXRα蛋白的表达明显增多(均P<0.01).与模型组相比,贞清方治疗组大鼠FBG水平、血清TG水平、肝脏指数及肝脏TG含量明显降低(10.94±3.33 mmol/L vs 16.67±4.33 mmol/L; 0.79±0.27 mmol/L vs 1.33±0.33 mmol/L; 5.72±0.81vs 7.61±1.24; 0.041±0.0110 mmol/g vs 0.059±0.0160 mmol/g,均P<0.01),肝脏脂肪变明显改善,肝脏LXRα mRNA、SREBP-1c mRNA和LXRα蛋白的表达明显减少(0.75±0.11 vs1.23±0.17,0.68±0.16 vs 1.07±0.14,0.220±0.071 vs 0.334±0.037,均P<0.01).结论:贞清方对2型糖尿病性非酒精性脂肪肝具有一定的治疗作用,且其治疗作用可能与贞清方能下调非酒精性脂肪肝组织LXRα的表达有关.     

非酒精性脂肪肝大鼠L-FABP和PPAR-α mRNA的动态表达

目的:检测非酒精性脂肪肝大鼠肝脏中L-FABP、PPAR-α mRNA的动态变化,探讨非酒精性脂肪肝的发病机制. 方法:♂大鼠84只,体质量180 g±10 g,随机分为饮食基础饲料的正常对照组和饮食高脂饲料的实验组;各组又随机分为0、2、4、8、12、16、18 wk 7个时相组,其中高脂饲料组在12 wk以后饮食正常饲料,使其脂肪肝处于自然恢复状态.分别于不同时相从心脏取血,测定血清中ALT、TG、CHOL、HDL-C和LDL-C的含量:收集肝脏标本,分别进行病理学检测和L-FABP和PPAR-α mRNA的动态变化检测. 结果:对照组大鼠肝脏L-FABP和PPAR-α mRNA在不同时相间的表达无显著性变化.高脂饮食脂肪肝大鼠第2周时病理切片没有观察到脂肪变性.L-FABPmRNA在第4周升高(0.59±0.06 vs 0.52±0.03,P<0.05),第8、12周显著升高(0.91±0.07,0.92±0.08 vs 0.52±0.03,均P<0.01),正常饮食6 wk后显著下降(0.59±0.04 vs 0.92±0.08,P<0.01),但是与对照组比较仍升高(P<0.05).PPAR-α mRNA在第4周下降(1.05±0.09 vs 1.13±0.07,P<0.05),第8、12周显著下降(0.89±0.04,0.85±0.07 vs 1.13±0.07,均P<0.01),正常饮食6 wk后显著升高(1.04±0.07 vs 0.85±0.07,P<0.01),但是与对照组比较仍下降(P<0.05).脂肪变性面积在第12周时最大,但未见明显的炎症反应,正常饮食6 wk后脂肪变性明显好转. 结论:高脂饮食脂肪肝大鼠模型L-FABP mRNA表达阈值的出现和PPAR-α mRNA表达下调可能在脂肪变性形成过程中起到重要作用,且单纯脂肪变性在一定程度上是可以通过饮食调节自然恢复的.     

维生素E、硒对非酒精性脂肪肝大鼠肝细胞色素P4501A1及脂质过氧化的干预作用

目的:研究维生素E、硒对非酒精性脂肪肝大鼠肝细胞色素P4501A1及脂质过氧化的干预作用.方法:♂SD大鼠,随机均分为5组:对照组(普通饲料)、模型组(高脂饲料)、VE干预组、Se干预组、VE Se干预组,建模5wk处死全部大鼠.生化方法检测血清及肝组织超氧化物歧化酶(SOD)和丙二醛(MDA)含量的变化,逆转录聚合酶链反应(RT-PCR)测定肝细胞色素P4501A1mRNA表达的变化,免疫组化方法测定肝组织中肿瘤坏死因子-α(TNF-α)、核因子-κB(NF-κB)表达的变化.结果:与对照组比较,模型组血清及肝组织中SOD显著降低(312.72±49.51kU/Lvs583.23±63.37kU/L;8.13±0.63U/mgprot.vs13.99±2.33U/mgprot.,P<0.01),MDA增高(13.40±4.24mmol/Lvs6.43±1.76mmol/L;9.79±0.94nmol/mgprot.vs6.80±0.97nmol/mgprot.P<0.01),细胞色素P4501A1mRNA表达水平,肝组织TNF-α、NF-κB蛋白表达明显增强(0.628±0.116vs0,0.230±0.013vs0.03±0.006,0.069±0.01vs0.003±0.001;P<0.05).与模型组比较VE组、Se组的血清及肝组织中SOD增高,MDA降低,细胞色素P4501A1mRNA表达水平略下降;肝组织TNF-α、NF-κB蛋白表达下降(P<0.05).VE Se组与模型组比较,血清SOD明显增高,其值接近对照组水平;细胞色素P4501A1mRNA表达水平显著下降(0.324±0.070vs0.628±0.116,P<0.05).结论:非酒精性脂肪肝的脂质过氧化损伤及相关因子的表达可能与肝细胞色素P4501A1表达上调有关.VitE和硒能提高机体的抗氧化能力,对非酒精性脂肪肝有保护作用,二者联合作用更明显.     

中药降脂颗粒对非酒精性脂肪肝大鼠肝脏瘦素受体mRNA及P-JAK2/P-STAT3的影响

目的:观察降脂颗粒对非酒精性脂肪肝大鼠的治疗作用及其对血清瘦素、肝组织瘦素受体mRNA、P-JAK2/P-STAT3蛋白含量表达的影响.方法:将60只SD♂大鼠,随机分为空白组(正常饮食)和造模组(高脂饮食).待造模成功后将造模组大鼠随机分为模型对照组、降脂颗粒低、中、高剂量组和东宝甘泰组.治疗4 wk后行肝组织生化和病理学检测,并同时应用ELISA试剂盒检测血清瘦素,RT-PCR法检测肝组织瘦素受体mRNA表达,应用Western blot检测肝组织P-JAK2和P-STAT3蛋白的表达.结果:低、中、高剂量组降脂颗粒能明显降低非酒精性脂肪肝大鼠模型肝脂(TG和TC)水平,改善脂肪变性,降低肝脏炎症反应,并能明显降低血清瘦素高水平状态(193.02±23.8 ng/L,163.97±31.38 ng/L,147.83±17.59 ng/L vs 317.22±39.26 ng/L,P＜0.01),改善瘦素抵抗,同时增加瘦素受体mRNA的表达(1.87±0.06,2.20±0.04,2.78±0.04 vs 1.50±0.05,P＜0.01),增加肝组织P-JAK2和P-STAT3蛋白的含量(119.88±2.98,123.45±0.68,124.34±3.42 vs 113.15±1.27,P＜0.01;94.15±0.78,100.18±3.33,101.94±2.20 vs 89.06±0.69,P＜0.01).结论:降脂颗粒对非酒精性脂肪肝大鼠肝脏脂质和炎症有较好的治疗作用,其可能机制是改善瘦素抵抗,增加肝脏瘦素受体mRNA表达及P-JAK2,P-STAT3蛋白含量.     

T辅助细胞亚群在大鼠非酒精性脂肪性肝病模型中的变化

目的:探讨T辅助细胞亚群Th1/Th2和Treg在非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)发病机制中的意义.方法:SD大鼠正常喂养1 wk后,随机分为正常组(n=20)和高脂饮食组(n=20).正常组大鼠以普通饲料喂养,高脂饮食组以高脂饲料喂养.实验第8、16周分批处死大鼠.观察肝组织的病理改变.荧光定量PCR方法检测肝脏TNF-α、IFN-γ、IL-4和Foxp3的基因表达.结果:高脂饮食8 wk大鼠肝细胞脂肪变明显,无明显炎症改变,IFN-γ、IL-4在肝脏的基因表达与正常组比较无明显变化,TNF-α稍升高,但无统计学意义,Foxp3 mRNA的表达比正常组明显降低(ct值:26.12±0.69 VS 24.22±0.62,P<0.05).高脂饮食16 wk大鼠脂肪肝明显,炎症明显,IFN-γ和TNF-α基因表达均显著升高(ct值:24.52±0.87 vs 29.94±1.44,24.31±1.13vs28.88±1.95,均P<0.05),IL-4与正常组相比较无明显变化,Foxp3基因表达较正常组和高脂饮食8 wk时均显著降低(ct值:32.57±1.54 vs 24.29±1.08,26.12±0.69,P<0.05).结论:高脂饮食大鼠肝脏Foxp3和Treg表达减少可能是高脂饮食NAFLD发生发展的重要因素.IFN-γ和TNF-α的联合作用加重了肝脏的炎症损伤.     

二甲双胍对高脂饲养大鼠肝脏脂肪变的干预作用

目的:探讨胰岛素抵抗在非酒精性脂肪性肝发病中的作用及机制,观察二甲双胍对高脂饲养大鼠肝脏脂肪变的干预效果.方法:21只(?) Wistar大鼠分为3组,每组7只,普通饮食组(SD),高脂饮食组(HF),二甲双胍组(HF- Met)在高脂饮食的同时给予二甲双胍,共8wk.8 wk末处死大鼠,称量附睾脂肪,计算肝指数,生化方法测定ALT、AST、TG、TC、FFA、SOD和MDA.放免法测定空腹胰岛素,逆转录聚合酶链反应(RT-PCR)和ELISA法检测肝脏TNF-αmRNA和蛋白的表达,用葡萄糖输注率(GIR)来评价胰岛素敏感性,并观察肝组织病理变化.结果:与HF相比,HF-Met肝细胞脂肪变和小叶炎症明显减轻,肝指数、胰岛素、AST、ALT、TG、FFA显著下降(3.25±0.26 vs 4.29±0.12,33.37±8.34 vs 46.73±5.24,17.29±5.34 vs 43.48±6.21,4.10±2.47 vs 12.05±4.05,P<0.01;106.0±31.04 vs 141.37±24.87,48.31±16.11 vs 88.34±21.94,P<0.05)TNF-α的表达也显著下降,GIR增加(7.58±1.05 vs 6.31±1.28,P<0.05).结论:二甲双胍干预能明显改善高脂饲养大鼠的胰岛素抵抗,降低肝脏TG、FFA和TNF-α的表达,减轻肝脏脂肪变的程度,提示胰岛素增敏治疗可能是NAFLD防治的一种积极策略.     

mtTFA、NRF-1对冷保存-再灌注肝移植大鼠线粒体DNA ATPase6基因表达的调节

目的:研究线粒体DNA上游调节基因mtTFFA和NRF-1对冷保存肝移植大鼠肝细胞线粒体DNA ATPase6基因表达的影响,探讨mtTFA和NRF-1对冷保存肝移植大鼠肝细胞线粒体DNA调节作用及其机制.方法:Wistar大鼠186R,采用改良"二袖套法"制作大鼠肝移植模型,动物随机分为A组:冷保存30 min;B组:冷保存6 h:C组:冷保存12 h;和D组(假手术对照组),分别于制模后于12 h、24 h、3 d、5 d、7 d采集标本,保证每时相点存活大鼠6R.观察各组大鼠肝脏ATP含量.采用RT-PCR方法检测mtDNAATPase6 mRNA、mtTFA和NRF-1 mRNA的表达变化.结果:冷保存再灌注后早期(12 h),A、B、C三组mtTFA mRNA表达降低,与A、B组相比,C组最为显著(0.57±0.05 vs 0.87±0.11,0.69±0.10,P<0.05).NRF-1 mRNA表达变化与mtTFA mRNA相一致.24 h后各组mtTFA及NRF-1 mRNA表达开始升高,ATPase6表达和肝组织ATP含量也升高,并且升高趋势与mtTFA及NRF-1 mRNA表达增高基本一致.结论:mtTFA和NRF-1可能通过基因转录调节ATPase6基因表达,改变线粒体呼吸链转运电子、合成ATP的能力.     

吡格列酮对SD大鼠非酒精性脂肪肝病形成的预防作用及其机制

目的:探讨吡格列酮(pioglitazone,PIO)对SD大鼠非酒精性脂肪肝病(non-alcoholic fatty liverdisease,NAFLD)形成的干预作用及机制.方法:♂SD大鼠72只,随机分为正常饮食组(NG)、高脂饮食组(HG)和PIO干预组(PIOG)各24只.PIOG喂饲高脂饲料,并同时予PIO药物灌胃8 wk.正糖高胰岛素钳夹实验检测IR水平,放免法和全自动生化仪检测血清生化指标,RT-PCR检测过氧化物酶体增殖物激活受体(peroxisome proliferator-activated receptorγ,PPARγ)mRNA表达,Western blot检测肝组织c-Jun氨基末端激酶(c-Jun amino-terminalkinase 1,JNK1)和PPARγ蛋白表达.结果:HG大鼠GIR水平降低和JNK1蛋白表达增高,均呈明显时间依赖性(均P<0.05);8 wk末HG大鼠肝细胞出现明显脂肪变性,与NG相比,体质量、肝指数,TG、ALT、AST、FFAs、FINS、TNF-α水平明显增高,IR加重,JNK1蛋白表达明显升高,肝组织PPARγ表达明显降低(TG:1.23±0.08 vs 0.62±0.12,ALT:92.80±7.09 vs 51.34±8.12;AST:153.22±20.65 vs 119.26±13.61;FFAs:511.94±24.88vs 335.31±15.71;FINS:41.23±1.84 vs 22.65±2.25;TNF-α:1.02±0.12 vs 0.34±0.07,均P<0.05);而PIOG大鼠,上述各项指标均得到明显改善,但仍不能完全达到NG大鼠水平(均P<0.05).结论:PIO对于由高脂饮食诱导的NAFLD的形成及其他IR相关疾病有预防作用.     

非酒精性脂肪性肝病大鼠肝脏解偶联蛋白2表达及其与能量贮备的关系

目的探讨非酒精性脂肪性肝病(NAFLD)大鼠肝脏线粒体解偶联蛋白2(UCP2)表达及其与能量贮备的关系。方法模型组SD大鼠给予高脂肪高胆固醇饮食饲养,分批于实验第8、12、16、24 周处死,同期设普通饮食饲养大鼠作对照。免疫组织化学和逆转录聚合酶链反应(RT-PCR)检测肝脏UCP2 mRNA转录及其蛋白表达。荧光测定法检测肝脏三磷酸腺苷(ATP)含量。结果模型组大鼠8周呈现单纯性脂肪肝,12-24周从脂肪性肝炎进展为脂肪性肝炎伴肝纤维化。免疫组织化学和RT-PCR显示,随着造模时间延长,模型组肝脏UCP2表达逐渐增强,UCP mRNA转录于24周达高峰,较对照组升高4.2倍, t=16.474,P<0.01;模型组肝脏ATP含量则随造模时间延长而逐渐减低,24周为(1.99±0.66) ×108μmol/g,对照组为(2.97±0.48)×108μmol/g,t=3.248,P<0.01。模型组肝脏UCP2 mRNA 转录的相对数值与其ATP含量呈密切负相关,r=-0.93,P<0.01。结论持续24周高脂饮食成功复制大鼠NAFLD模型,模型大鼠肝脏UCP2表达增强而ATP含量减少,两者之间关系密切。     

Three layer functional model and energy exchange concept of aging process

Relying on a certain degree of abstraction, we can propose that no particular distinction exists between animate or living matter and inanimate matter. While focusing attention on some specifics, the dividing line between the two can be drawn. The most apparent distinction is in the level of structural and functional organization with the dissimilar streams of ‘energy flow’ between the observed entity and the surrounding environment. In essence, living matter is created from inanimate matter which is organized to contain internal intense energy processes and maintain lower intensity energy exchange processes with the environment. Taking internal and external energy processes into account, we contend in this paper that living matter can be referred to as matter of dissipative structure, with this structure assumed to be a common quality of all living creatures and living matter in general. Interruption of internal energy conversion processes and terminating the controlled energy exchange with the environment leads to degeneration of dissipative structure and reduction of the same to inanimate matter, (gas, liquid and/or solid inanimate substances), and ultimately what can be called ‘death.’ This concept of what we call dissipative nature can be extended from living organisms to social groups of animals, to mankind. An analogy based on the organization of matter provides a basis for a functional model of living entities. The models relies on the parallels among the three central structures of any cell (nucleus, cytoplasm and outer membrane) and the human body (central organs, body fluids along with the connective tissues, and external skin integument). This three-part structural organization may be observed almost universally in nature. It can be observed from the atomic structure to the planetary and intergalactic organizations. This similarity is corroborated by the membrane theory applied to living organisms. According to the energy nature of living matter and the proposed functional model, the decreased integrity of a human body's external envelope membrane is a first cause of the structural degradation and aging of the entire organism. The aging process than progresses externally to internally, as in single cell organisms, suggesting that much of the efforts towards the restoration and maintenance of the mechanisms responsible for structural development should be focused accordingly, on the membrane, i.e., the skin. Numerous reports indicate that all parts of the human body, like: bones, blood with blood vessels, muscles, skin, and so on, have some ability for restoration. Therefore, actual revival of not only aging tissue of the human body's membrane, but the entire human body enclosed within, with all internal organs, might be expected. We assess several aging theories within the context of our model and provide suggestions on how to activate the body's own anti-aging mechanisms and increase longevity. This paper presents some analogies and some distinctions that exist between the living dissipative structure matter and inanimate matter, discusses the aging process and proposes certain aging reversal solutions.     

Unusual responses of nocturnal pineal melatonin synthesis and secretion to swimming: Attempts to define mechanisms

Abstract: The effect of swimming at night on rat pineal melatonin synthesis was compared with that of light exposure at night. Rats were forced to swim at 0030 hr (lights out at 2000 hr) and sacrificed by decapitation 15 and 30 min later, immediately after swimming. Other groups of animals were exposed to white light (650μW/cm²) for 15 and 30 min at same time. Swimming caused a rapid and highly significant drop in the melatonin content in the pineal gland; however, the activity of N-acetyltransferase (NAT), the supposed rate limiting enzyme in the melatonin production, was not changed. Despite the drop in pineal melatonin levels, serum concentrations of the indole remained elevated in the rats that swam. In contrast, melatonin levels in the pineal and serum of light exposed rats fell precipitously, accompanied by a significant suppression of NAT activity. Since we anticipated that the strenuous exercise associated with swimming may induce release of artrial natriuretic peptide (ANP) from the heart, which in turn could cause the release of pineal melatonin, in a second study we injected physiological saline intravenously to stretch the cardiac muscle and release ANP. Three milliliters of normal saline was injected during the day into the jugular vein of anesthetized rats that were pretreated with isoproterenol to stimulate pineal melatonin production. Animals were killed 15 min after the saline injection, and pineal NAT activity and pineal melatonin levels were measured. The saline injections caused no alteration in the elevated levels of either NAT or melatonin. These data suggest that the disparity in pineal NAT activity (which was high) and pineal melatonin (which was low), in animals swum at night, may not be caused by ANP which is released during strenuous exercise such as swimming.     

Melatonin and photoperiodic time measurement: Seasonal breeding in the sheep

Abstract: Well-established circadian physiology supports the view that photoperiodic time measurement utilizes the coincidence between the presence of light and a photosensitive phase of a 'biological clock' to alter reproductive status—the so-called external coincidence model of seasonal breeding. In this review, we examine the mechanism whereby photoperiod interacts with presumed suprachiasmatic nuclei activity to allow endogenous melatonin to normally synchronize reproductive activity to the optimal time of year. The Romney Marsh sheep is particularly explored as an experimental model. It is suggested that the on/off activity of seasonal reproduction may be a robust mechanism able to be predictably manipulated by the judicious use of the light/dark cycle and exogenous melatonin, but firmly based on circadian principles.     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Serological survey of HIV and syphilis in pregnant women in Madagascar

Objectives Peripartal transmission of human immunodeficiency virus (HIV) and Treponema pallidum, the causative agent of syphilis, leads to severe consequences for newborns. Preventive measures require awareness of the maternal infection. Although HIV and syphilis testing in Madagascar could be theoretically carried out within the framework of the national pregnancy follow‐up scheme, the required test kits are rarely available at peripheral health centres. In this study, we screened blood samples of pregnant Madagascan women for HIV and syphilis seroprevalence to estimate the demand for systemic screening in pregnancy. Methods Retrospective anonymous serological analysis for HIV and syphilis was performed in plasma samples from 1232 pregnant women that were taken between May and July 2010 in Ambositra, Ifanadiana, Manakara, Mananjary, Moramanga and Tsiroanomandidy (Madagascar) during pregnancy follow‐up. Screening was based on Treponema pallidum haemagglutination tests for syphilis and rapid tests for HIV, with confirmation of positive screening results on line assays. Results Out of 1232 pregnant women, none were seropositive for HIV and 37 (3%) were seropositive for Treponema pallidum. Conclusions Our findings are in line with previous studies that describe considerable syphilis prevalence in the rural Madagascan population. The results suggest a need for screening to prevent peripartal Treponema pallidum transmission, while HIV is still rare. If they are known, Treponema pallidum infections can be easily, safely and inexpensively treated even in pregnancy to reduce the risk of transmission.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

Variabilité des concentrations plasmatiques de l’angiotensinogène et risque d’hypertension artérielle chez le rat transgénique

Aim

Genetic polymorphisms of the human angiotensinogen gene are frequent and may induce up to 30% increase of plasma angiotensinogen concentrations with a blood pressure increase of up to 5 mmHg. Their role for the pathogenesis of human arterial hypertension remains unclear. High plasma angiotensinogen levels could increase the sensitivity to other blood pressure stressors.

Methods

Male transgenic rats with a 9-fold increase of plasma angiotensinogen concentrations and male non-transgenic rats aged 10 weeks were treated or not with NG-Nitro-L-arginine-methyl ester for 3 weeks in their drinking water (n = 3/group). Systolic blood pressure and body weight were measured at baseline and at the end of the study when left ventricular weight and ventricular expression of angiotensin I-converting enzyme and procollagen Iα1 were determined (polymerase chain reaction).

Results

At baseline, transgenic rats had +18 mmHg higher bood pressure and –8% lower body weight compared to non-transgenic rats (P < 0.05) without significant changes for the vehicle groups throughout the study (P > 0.05). NG-Nitro-L-arginine-methyl ester increased blood pressure, left ventricular weight and left ventricular weight indexed for body weight by +41%, +17.6% and +18.6% (P < 0.05) in transgenic and +25%, +5.3% and +6.7% (P > 0.05) in non-transgenic rats compared to untreated animals, respectively. Cardiac gene expression showed no differences between groups (P > 0.05).

Conclusion

Increased plasma angiotensinogen levels may sensitize to additional blood pressure stressors. Our preliminary results point towards an independent role of angiotensinogen in the pathogenesis of human hypertension and associated end-organ damage.