免疫刺激序列增强日本血吸虫DNA疫苗的免疫保护作用

目的　探讨免疫刺激序列在日本血吸虫Mr 23 000膜蛋白 (SjC23)DNA疫苗诱导BALB/c小鼠抗血吸虫感染中的作用。　方法　将SjC23基因片段克隆到增加了免疫刺激序列的真核表达质粒 pcDNA3.1-CpG中,构建pcDNA3.1-SjC23/CpG。 40只雌性BALB/c小鼠随机分为 4组 ,① pcDNA3.1对照组 ;②pcDNA3.1-SjC23组 ;③ pcDNA3.1-CpG组 ;④ pcDNA3.1-SjC23/CpG组。每鼠经两侧股四头肌注射质粒DNA共100 μg ,隔 2周加强免疫 1次 ,共 3次。末次免疫后 4周经腹部皮肤感染日本血吸虫尾蚴 45条 /鼠 ,45d后计数成虫及肝脏虫卵数。首次免疫前和感染前 2d分别经尾静脉采血 ,检测IgG及IgG1、IgG2a。末次免疫后 3周取小鼠脾细胞 ,检测经伴刀豆球蛋白和SjC23重组蛋白刺激后小鼠白细胞介素 2 (IL-2 )、白细胞介素 4(IL-4)和γ干扰素 (IFN-γ)。用51Cr释放法检测经SjC23重组蛋白刺激后脾细胞对小鼠淋巴瘤细胞的杀伤作用。　结果　②组和④组减虫率分别为 2 8.1%和 3 5.1% ,减卵率分别为 2 1.6%和 2 6.5 %。④组减虫率显著高于②组 (P <0.0 5 )。这两组均检测到特异性IgG ,IgG2a/IgG1比值分别为 10.1和 12.2。脾细胞经伴刀豆球蛋白和SjC23重组蛋白刺激后的IL-2水平 ,②组较①组、④组较③组均有升高。②组脾细胞对靶细胞的杀伤活性为9.7%, ④组为40.0%。 结论 疫苗载体中增加免疫刺激序列，可提高SjC23 DNA 疫苗在BALB/c小鼠中诱导产生的免疫保护作用。     

日本血吸虫复合表位DNA疫苗免疫保护作用的研究

目的研究日本血吸虫复合表位DNA疫苗诱导BALB/c小鼠抗血吸虫感染的免疫保护作用。方法将40只雌性BALB/c小鼠随机分为4组:pcDNA3.1组(对照组),每鼠经两侧股四头肌注射100μg pcDNA3.1质粒DNA,每侧50μg;TPI组,每鼠肌注100μg pcDNA3.1-TPI质粒DNA;TP组,每鼠肌注100μg pcDNA3.1-T-linker-P质粒DNA;PT组,每鼠肌注100μg pcDNA3.1-P-linker-T质粒DNA。每隔2周加强免疫1次,剂量和方法相同,共免疫3次。末次免疫后4周每鼠经腹部皮肤攻击感染(45±1)条日本血吸虫尾蚴,45d后剖杀,计数成虫及肝脏虫卵数。首次免疫前2 d及感染前2 d尾静脉采血,间接ELISA检测特异IgG及IgG1I、gG2a水平。末次免疫后3周,每组取2只小鼠制备脾细胞,双抗体夹心法检测脾细胞经ConA和rSjCTPI刺激后培养上清中的IL-2I、L-4和IFN-γ水平。结果TP组和PT组小鼠减虫率分别为34.76%和36.14%,显著高于TPI组(P<0.05)和对照组(P<0.01);减卵率分别为51.20%和50.79%,与TPI及对照组比较差异有显著性(P<0.05)。TP组和PT组小鼠血清特异性IgG水平均升高(P<0.05),IgG2a/IgG1的比值分别为4.23和4.34。脾细胞经ConA和rSjCTPI刺激后,IL-2水平TP组和PT组较对照组均升高。结论复合表位DNA疫苗能诱导小鼠产生抗血吸虫感染的免疫保护力,效果优于rSjCTPI疫苗。     

日本血吸虫23kDa膜蛋白DNA疫苗保护性免疫及IL—12免疫佐剂作用的研究

目的研究日本血吸虫中国大陆株23 kDa膜蛋白(SjC23)DNA疫苗诱导BALB/c小鼠免疫保护作用以及IL-12的免疫增强效果.方法56只BALB/c雌性小鼠随机分为A、B、C、D 4组,每组14只.A组(对照组),于每鼠两腿股四头肌注射100μgpcDNA3.1质粒DNA;B组(SjC 23组),注射100μgpcDNA3.1-SjC 23质粒DNA;C组(SjC 23+IL-12DNA组),注射100μgpcD-NA3.1-SjC 23、100μgpcDNA3.1-p35、100μgpcDNA3.1-p40质粒DNA的混合液;D组(SjC23+rIL-12蛋白组),免疫剂量同SjC23组.共免疫3次,每次免疫间隔2周,剂量和方法同第1次.于末次免疫后1个月,每鼠攻击感染(45±2)条日本血吸虫中国大陆株尾蚴.但D组的小鼠在攻击感染当天,及感染后第2、4、6天经腹腔注射0.2μg/鼠rIL-12蛋白.攻击后45 d剖杀小鼠,计数成虫及肝内虫卵数.于末次免疫后2周对照组及SjC23组用51Cr释放法测定SjC 23介导的特异性细胞毒作用;用脾细胞培养法检测经重组日本血吸虫23 kDa膜蛋白亲水区大片段融合蛋白(GST-HD)刺激后,在免疫后及攻击后小鼠脾细胞IL-2、IL-4、IL-10和IFN-γ的水平.分别于攻击前后2周经小鼠尾静脉采血,用ELISA法检测血清中抗SjC 23抗体.结果51Cr释放法测定SjC 23介导的特异性细胞毒作用,SjC 23组获得了56.4%的细胞毒活性,而对照组为25.8%;细胞因子IL-2和IFN-γ的水平在攻击前、后SjC 23组较对照组有明显的升高,而IL-4和IL-10则无变化.ELISA法检测抗SjC 23抗体结果表明,免疫后2周,SjC 23组4/10份血清为阳性,SjC 23+IL-12 DNA组5/10份血清阳性,SjC23+rIL-12蛋白组5/10份血清阳性.动物保护性实验结果显示,与对照组相比,B、C组和D组分别获得了28.1%、40.1%和41.7%的减虫率,减卵率分别为37.9%、53.3%和51. 7%,加用IL-12的C组和D组与单独使用SjC 23的B组相比减虫率和减卵率均显著增加(P＜0.05).结论SjC 23 DNA疫苗具有诱导BALB/c小鼠产生部分抗血吸虫免疫作用,IL-12作为细胞因子佐剂具有提高SjC 23 DNA疫苗免疫保护性的作用.     

CpG免疫刺激序列增强日本血吸虫TPIDNA疫苗免疫保护作用的研究

目的研究CpG免疫刺激序列对日本血吸虫中国大陆株磷酸丙糖异构酶DNA疫苗诱导BALB/c小鼠免疫保护的增强作用.方法设计合成一对含6个免疫刺激序列的寡脱氧核苷酸,克隆到真核表达载体pcDNA3.1第5314碱基Ssp I酶切位点,改建为pcDNA3.1-CpG.再将SjCTPIDNA片段克隆到pcDNA3.1-CpG的多克隆位点区,构建为pcDNA3.1-TPI/CpG.56只BALB/c雌性小鼠随机分为4组,各组小鼠分别肌肉注射pcDNA3.1、pcDNA3.1-TPI、pcDNA3.1-CpG、pcD-NA3.1-CpG/TPI质粒DNA,每鼠100 μg.每隔2周加强免疫1次,共3次.末次免疫后4周每鼠经腹部皮肤攻击感染(45士1)条日本血吸虫尾蚴,45 d后剖杀,计数成虫及肝脏虫卵数.首次免疫前2d及攻击感染前2 d经尾静脉采血检测抗体水平、抗体亚类IgG1、IgG2a.末次免疫后2周制备脾细胞,检测细胞因子IL-2、IL-4、IFN-γ的水平.结果 pcDNA3.1-TPI组和pcDNA3.1-TPI/CpG组小鼠血清都检测到特异性IgG抗体,抗体亚类IgG2./IgG1的比值分别为1.76和2.67,而其他两组则未检测到特异性IgG抗体;pcDNA3.1-TPI组和pcDNA3.1-TPI/CpG组小鼠的IL-2、IFN-γ较对照组均有不同程度的升高,IL-4无明显差异;pcDNA3.1-TPI组和pcDNA3.1-TPI/CpG组分别获得了25.98%和34.54%的减虫率,后者高于前者,并分别获得了27.68%和29.50%的减卵率.结论 CpG免疫刺激序列似能增强DNA疫苗在小鼠体内诱导的Th1型免疫应答,并提高DNA疫苗的免疫保护作用.     

日本血吸虫23kDa膜蛋白DNA疫苗抗病免疫作用的研究

目的探讨日本血吸虫SjC23 DNA疫苗对血吸虫肝脏虫卵肉芽肿的免疫调节作用,以评价其作为抗病疫苗的潜能。方法 30头松江猪分为3组。A组(SjC23组)每头猪于两侧臀部肌注500μgpcDNA3.l-SjC23质粒 DNA;B组(SjC23+IL-12)每头猪肌注500μg pcDNA3.1-SjC23 DNA疫苗及500μgpcDNA3.1-P 35和500μg pcDNA3.1-P40质粒DNA的混和物;C组(对照组),每头猪肌注500μgpcDNA3.1质粒DNA。于第0、3、6周共免疫3次。末次免疫后30天,每头猪采用背部贴片法攻击感染600条日本血吸虫尾蚴,攻击后45天剖杀实验猪,取肝脏,于同一部位切取1.5cm~3的肝组织。按常规法制备石腊切片。切片在NYD-1000型图象分析系统下观察,测定所有肉芽肿的面积和直径,并比较。结果与对照组相比,SjC23组及SjC23+IL-12组肉芽肿内炎性细胞明显减少。肉芽肿平均面积较对照组分别减小48.57％和44.37％,肉芽肿直径分别减小27.56％和 22.78％。结论 SjC23 DNA疫苗具有下调血吸虫肝脏虫卵肉芽肿的作用,可望成为一种血吸虫病抗病疫苗候选分子。     

日本血吸虫中国大陆株23 kDa膜蛋白DNA疫苗诱导小鼠保护性免疫的研究

目的　研究日本血吸虫中国大陆株 2 3kDa膜蛋白 (SjC2 3)DNA疫苗诱导C5 7BL/6小鼠免疫保护作用。方法　将全长的SjC2 3基因克隆到真核表达载体pcDNA3.1,构建DNA疫苗 pcDNA3.1 SjC2 3。制备SjC2 3及IL 12的两个亚单位 p35、p4 0的DNA疫苗和对照 pcDNA3.1。 4 8只C5 7BL/6小鼠随机分为A、B、C 3组。A组小鼠肌注 10 0 μgpcDNA3.1;B组注射 10 0 μg pcDNA3.1 SjC2 3;C组肌注 pcDNA3.1 SjC2 3、pcDNA3.1 p35及pcDNA3.1 p4 0各 10 0 μg的混合物。每隔 2周各免疫 1次 ,共 3次。第 8周每鼠感染 4 5± 2条 /只尾蚴 ,4 5d后剖杀 ,计数成虫及肝内虫卵。采用免疫组化法检测SjC2 3及 p35、p4 0在小鼠局部组织内的表达 ;用脾细胞培养法检测经rSjC2 3 HD刺激后 ,攻击前、后小鼠脾细胞IL 2、IL 4、IL 10和IFN γ的水平。用Westernblotting检测血清中抗SjC2 3抗体。结果　SjC2 3以及p35、p4 0在免疫小鼠股四头肌细胞膜和细胞浆均获得表达。IL 2和IFN γ的水平攻击前、后在B组和C组均明显升高。Westernblotting检测抗SjC2 3抗体结果表明 ,免疫后两周 ,B组 8/10份血清为阳性 ,C组 9/10份血清阳性。B组和C组分别获得 2 6 .9%和 35 .4 %的减虫率 ,C组显著高于B组 (P <0 .0 5 ) ;减卵率分别为 2 2 .2 %和 2 8.4 %。结论　SjC     

日本血吸虫多价DNA疫苗免疫保护作用的研究

目的研究日本血吸虫多价DNA疫苗诱导BALB/c小鼠的免疫保护作用.方法65只BALB/c雌性小鼠随机分为5组,各组小鼠分别肌肉注射纯化的质粒DNA pcDNA3.1(对照组)、pcDNA3.1-TPI(TPI)、pcDNA3.1-(CDR3)6[(CDR3)6]、pcDNA3.1-TPI-linker-(CDR3)6(TLC)和pcDNA3.1-(CDR3)6-linker-TPI(CLT),每鼠100μg.每隔2周加强免疫1次,共3次.末次免疫后4周每鼠经腹部皮肤攻击感染(45±1)条日本血吸虫尾蚴,45 d后剖杀,计数成虫及肝脏虫卵数.首次免疫前2天及感染前2天经尾静脉采血检测IgG抗体水平、抗体亚类IgG1、IgG2a.末次免疫后2周取小鼠脾脏制备单个脾细胞,检测细胞因子IL-2、IL-4、IFN-γ的水平.结果TPI、TLC组和CLT组小鼠血清都检测到特异性IgG抗体,抗体亚类IgG2a/IgG1的比值分别为1.71、2.71和4.70,而其他两组则未检测到特异性IgG抗体;TPI、TLC组和CLT组小鼠的IL-2、IFN-γ较对照组均有不同程度的升高,IL-4则无明显差异.多价DNA疫苗TLC组和CLT组减虫率分别达到37.30%、39.09%,减卵率分别为41.61%、49.54%,均显著高于TPI组和(CDR3)6组(P均＜0.05).结论多价DNA疫苗相对于单价DNA疫苗能诱导小鼠产生较高的免疫保护作用,且诱导宿主产生较高的以Th1为主的免疫应答.     

弓形虫主要表面抗原1核酸疫苗与蛋白疫苗联合免疫保护作用的研究

目的 研究刚地弓形虫RH株主要表面抗原1(P30)DNA疫苗诱导BALB/c小鼠的保护性免疫作用。方法 根据弓形虫P30基因的DNA序列设计一对引物,,将PCR扩增到的P30基因克隆到真核表达载体pcDNA.3.1中。大量制备pcDNA3. 1-P30和pcDNA3.1质粒DNA。将48只 BALB/c小鼠随机分成4组,每组1 2只,空质粒对照组(A组)第O、2、4周经小鼠股四头肌注射100 μg pcDNA3.1质粒DNA;重组P30抗原免疫组(B组)第0、2、4周每鼠经背部皮下多点注射50 μg rP30+福氏完全佐剂;P30 DNA疫苗免疫组(C组)第O、2、4周经小鼠股四头肌注射100 μg pcD- NA3. 1-P30质粒DNA;P30 DNA疫苗和重组P30抗原联合免疫组(D组)第O、2周经小鼠股四头肌洼射100 μg pcDNA3. 1-P30质粒DNA,第4周每鼠经背部皮下多点注射50 μg rP30+福氏完全佐剂。末次免疫4周后每鼠用100个弓形虫速殖子经腹腔感染,观察小鼠存活时间。结果 成功构建刚地弓形虫RH株P30DNA疫苗,动物保护性实验表明,虽然与对照组相比实验组小鼠的存活时间有一定的延长,但差异无显著性。结论 pcDNA3.1-P30 DNA疫苗具有弓形虫病候选DNA疫苗分子的潜力。     

日本血吸虫中国大陆株TPI DNA疫苗诱导BALB/c小鼠保护性免疫力的研究

目的研究日本血吸虫中国大陆株磷酸丙糖异构酶(SjCTPI)DNA疫苗诱导BALB/c小鼠的保护性免疫作用.方法将39只BALB/c小鼠随机分成3组A组(对照组),肌注pcDNA3.1质粒DNA 100μg/鼠;B组(实验组),每鼠肌注pcDNA3.1-SjCTPI 100μg;C组(加强组),每鼠肌注pcDNA3.1-SjCTPI 100μg及pcDNA3.1-P35和pcDNA3.1-P40的混合物100μg.每两周免疫1次,共计3次.末次免疫4周后,每鼠用45条尾蚴进行攻击,45 d后剖杀小鼠,计数成虫以及每鼠肝组织内虫卵数;于攻击前每组各取两只小鼠采用51Cr释放法测定SjCTPI介导的特异性细胞毒作用;ELISA检测攻击前后的抗TPI的抗体水平.结果用ELISA检测抗TPI抗体的结果表明,攻击前A组的10份血清均为阴性,B组5/10份血清出现弱阳性,C组也有6/10份血清出现弱阳性反应.51Cr释放法测定细胞毒活性结果表明,A、B、C组细胞毒活性分别为9.1%、27.6%和54.4%.与对照组相比,实验组的减虫率、减卵率分别为30.2%、52.9%;加强组的减虫率、减卵率分别为32.7%、47.0%.结论进一步证实了SjCTPI DNA疫苗作为抗血吸虫病核酸疫苗的潜力.     

日本血吸虫鸡尾酒式DNA疫苗与蛋白疫苗联合应用增强免疫保护作用的研究

目的 探讨日本血吸虫鸡尾酒式DNA疫苗与蛋白疫苗联合应用以增强免疫保护作用的效果。方法分别大量制备质粒DNA：pcDNA3．1-SjC23、pcDNA3．1-SjCTPI、pcDNA3．1-（CDR3）6和重组蛋白SjC23-HD、SjCTPI、NP30。pcDNA3．1-SjC23、pcDNA3．1-SjCTPI、pcDNA3．1-（CDR3）6等量混合后即为鸡尾酒式的混合DNA疫苗，重组蛋白SjC23-HD、SjCTPI、NP30等量混合后即为鸡尾酒式的混合蛋白疫苗。70只BALB／c小鼠随机分为A、B、C、D、E5组，每组14只。A组为自然感染组；B组（空质粒对照组）每只小鼠分别在第0、3、6周经股四头肌注射100μlpcDNA3．1；C组（空质粒＋混合蛋白对照组）每只小鼠分别在第0、3、6周经股四头肌注射100μlpcDNA3．1，第9周每鼠经背部皮下多点注射100μl混合蛋白疫苗＋100μl福氏完全佐剂（FCA）；D组（混合DNA组）每只小鼠分别在第0、3、6周经股四头肌注射100μl混合DNA疫苗；E组（混合DNA＋混合蛋白组）每只小鼠分别在第0、3、6周经股四头肌注射100μl混合DNA疫苗，第9周每鼠经背部皮下多点注射100μl混合蛋白疫苗＋100μlFCA。DNA免疫组末次免疫后4周，蛋白加强组末次免疫后2周，所有小鼠同时经腹部皮肤感染（40±1）条尾蚴。攻击感染后42d剖杀小鼠，计数成虫及肝脏虫卵数。首次免疫前2d及感染前2d分别经尾静脉采血，分离血清检测IgG抗体水平、抗体亚类IgG1及IgG2a，并取小鼠脾脏制备单个脾细胞，检测细胞因子IL-2、IL-4、IFN-γ的水平。结果C、D组和E组的减虫率分别为17．70％、32．88％和45．35％，D组和E组的减虫率均显著高于C组（P均〈0．01），且E组的减虫率显著高于D组（P〈0．01）；C、D组和E组的减卵率分别为9．39％、36．20％和48．54％，D组和E组的减卵率均显著高于C组（P均〈0．01），且E组的减虫率也显著高于D组（P〈0．05）。C、D、E3组小鼠血清都检测到特异性IgG抗体，?     

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.