慢性HBV感染者外周血单个核细胞CTLA-4基因多态性与病情转归的关联研究

目的初步探讨慢性HBV感染者外周血细胞毒性T淋巴细胞相关抗原-4（CTLA-4）基因第1外显子区49位基因单核苷酸多态性（single nucleotide polymorphism，SNP）与乙型肝炎病毒感染转归的关系。方法采用聚合酶链式反应-限制性片段长度多态性法检测190例慢性HBV感染者和93例既往HBV感染者外周血CTLA-4基因49位点的多态性。结果慢性HBV感染者CTLA-4基因49位点A／G基因型分布与对照组比较差异有显著性（P=0．034），慢性感染者G等位基因频率明显低于对照组（0．561对0．677，P=0．008，OR=0．607）。结论CTLA-4第1外显子49位基因多态性可能与乙型肝炎病毒感染慢性化相关。     

白细胞介素28B基因多态性与慢性HBV、HCV感染的相关性

HBV、HCV感染具有慢性化的流行特点。白细胞介素(IL)28B基因多态性与HBV、HCV感染慢性化及干扰素(IFN)抗病毒疗效具有相关性。简述了IL-28B生物学功能及特点,述评了IL-28B基因多态性与HCV感染的相关性,并归纳了目前发现的IL-28B基因多态性与HBV感染的相关性的众多研究报道。分析表明,IL-28B基因多态性与丙型肝炎病程转归及IFN抗病毒疗效的相关性研究报道较为一致;而IL-28B基因多态性与乙型肝炎病程转归,HBV感染后肝硬化、肝癌及IFN抗病毒疗效的相关性研究,各方学者均有不同的见解,尚需进一步的研究。     

乙型肝炎病毒基因变异与免疫调节的关系

目的探讨乙型肝炎病毒（HBV）基本核心启动子（BCP）及前C基因变异与慢性乙型肝炎患者外周血CD4^＋CD25^＋调节性T细胞水平的关系。方法应用基因芯片技术检测HBV BCP及前C基因T1762、A1764、A1896位碱基变化;应用流式细胞仪检测外周血CD4^＋CD25^＋调节性T细胞表达水平。结果急性乙型肝炎、慢性活动性乙型肝炎、肝硬化、肝癌患者血清中HBV DNA T1762、A1764、A1896位碱基突变率分别为0、41.2%、69.4%、100%;急性乙型肝炎、慢性活动性乙型肝炎、肝硬化、肝癌患者外周血CD4^＋CD25^＋调节性T细胞水平高于正常对照;HBeAg阳性感染者高于HBeAg阴性感染者;变异株感染者低于非变异株感染者（P均〈0.05）。结论前C/C基因变异与HBV感染后肝病的慢性化及临床病情加重有关,与CD4^＋CD25^＋调节性T细胞的表达水平相关。     

新疆维吾尔族慢性乙型肝炎患者HBV基因型分布及其特点

目的探讨新疆维吾尔族慢性乙型肝炎患者HBV基因型分布及其特点。方法采用型特异性引物巢式PCR法对127例维吾尔族慢性乙型肝炎患者进行基因分型,并测序验证。结果基因D型占39．4%（50/127）,基因B型占22．0%（28/127）,基因C型占16．5%（21/127）,基因BD混合型占9．4%（12/127）,基因CD混合型占8．7%（11/127）,基因BCD混合型占3．9%（5/127）; HBeAg阳性与HBeAg阴性的维吾尔族慢性乙型肝炎患者基因型分布,差异无统计学意义（x^2= 6．033,P＞0．05）;不同年龄维吾尔族慢性乙型肝炎患者HBV基因型分布差异无统计学意义（x^2= 3．137,P＞0．05）;不同性别维吾尔族慢性乙型肝炎患者HBV基因型分布差异亦无统计学意义（x^2= 8．058,P＞0．05）。结论新疆维吾尔族慢性乙型肝炎患者HBV基因型以D型占优势,其次可见B、C型及BD、CD、BCD混合型。同一疾病谱的慢性HBV感染者基因型分布可能与宿主HBeAg状态、年龄、性别无明显关系。     

RANTES基因多态性与乙型肝炎慢性化的相关性研究

目的探讨正常T细胞表达和分泌活性因子(RANTES)基因启动子区单核苷酸多态性与乙型肝炎慢性化的关系。方法采用聚合酶链反应-限制性片断长度多态性方法检测118例慢性乙型肝炎和61例急性乙型肝炎患者外周血RANTES基因启动子区-403、-28和In1.1三个基因位点基因分型。结果 CHB患者In1.1TC基因型(34.7%)及C等位基因频率(37.7%)明显高于对照组(21.3%,25.4%),差异有统计学意义(P﹤0.05);TC基因型慢性化的风险是TT基因型的2.2倍(OR=2.278,95%CI:1.079～4.808);多元Logistic回归分析显示TC基因型携带者与TT相比患慢性乙型肝炎的危险性增大。结论 RANTES In1.1基因位点多态性与乙型肝炎慢性化有关,携带In1.1TC基因型的HBV感染者易发生慢性化。     

雌激素受体基因α多态性与乙型肝炎病毒感染慢性化的相关性研究

目的 了解雌激素受体α基因XbaI和PvuII多态性与乙型肝炎病毒感染慢性化的关系,从基因水平上探讨慢性乙型肝炎的发病机制。方法 采用聚合酶链反应-限制性片段长度多态性法检测93例乙型肝炎病毒感染恢复期患者和169例慢性乙型肝炎患者雌激素α受体基因PvuII和XbaI多态性。结果 慢性乙型肝炎患者雌激素受体基因PvuII多态性的C／T基因型和c等位基因频率（52．7％,44．1％）明显高于乙型肝炎病毒感染恢复期患者（37．6％,29．6％）;TT基因型和T等位基因频率（29．5％,55．9％）明显低于后者（47．3％,70．4％）,差异有统计学意义（P〈0．05）;CT＋CC基因型乙型肝炎病毒感染慢性化的风险是TT基因型的2．54倍（OR=2．539,CI：1．50～4．29）。雌激素受体基因XbaI多态性分布在慢性乙型肝炎患者和乙型肝炎病毒感染恢复期患者间比较,差异均无统计学意义（P〉0．05）。结论 雌激素受体基因PvuII C/T基因型和C等位基因可能是乙型肝炎病毒感染慢性化的遗传易感基因。     

白细胞介素-6基因多态性与慢性HBV感染的相关性

目的：研究IL-6基因启动子区-174位点基因多态性与慢性HBV感染之间的关系。方法：应用序列特异性引物聚合酶链反应（polymerase chain reaction—sequence specific primer，PCR-SSP）技术检测62例慢性乙型肝炎（CHB）患者、60例慢性HBV携带者（Asymptomatic carrier，AsC）和63例健康对照者IL-6基因启动子区-174位点的基因型，进行相关性分析。结果：CHB患者、AsC和健康对照者之间IL-6基因启动子区-174位点的基因型分布频率没有显著性差异（P〉0．05）。结论：IL-6基因启动子区-174位点多态性与慢性HBV感染之间无明显相关性。     

人类白细胞抗原-DRB1*1001与慢性乙型肝炎重型化密切关联

人类白细胞抗原(HLA)复合体作为调节机体免疫应答的重要基因群,与抗乙型肝炎病毒(HBV)免疫反应有着密切的关系,某些特殊的HLA基因型可能影响着HBV感染的慢性化和重型化。利用聚合酶链反应/序列特异性引物(PCR/SSP)技术通过对慢性乙型肝炎和慢性重型乙型肝炎患者中HLA-Ⅱ类基因多态性的分析,从基因水平研究免疫遗传因素在慢性乙型肝炎重型化发病机制中的作用。     

干扰素-α/β受体基因多态性与HBV感染结局的关系

目的：探讨IFN-α/β受体基因多态性与HBV（乙肝病毒）感染不同临床转归之间的相关性。方法：应用基因测序检测80例自限性HBV感染者（SR组）和220例慢性持续性HBV感染者（PC组）[包括无症状HBV携带者（AsC组）88例和进展性肝病者132例（慢性乙型肝炎76例、肝硬化56例）]的IFN（干扰素）-α/β受体基因-568G→C、-408C→T两个位点的多态性,比较各组间基因型和等位基因频率。结果：①-568G→C位点多态性中,PC组总GG基因型频率比SR组显著升高,差异有显著性意义（P〈0.05）。等位基因G的频率,进展性肝病组均显著高于SR组（P〈0.05）。②-408C→T位点多态性中,进展性肝病组总CC基因型显著高于SR组（P〈0.05）,而肝硬化组和慢性乙型肝炎组之间,SR组和AsC组之间差异均无显著性。结论：IFN-α/β受体基因-568G→C、-408C→T两个位点的多态性,与HBV感染不同结局之间有关,携带-568G→C GG基因型和G等位基因的HBV感染者容易发展为慢性,G等位基因更趋向于进展性肝病,而携带-408C→T CC基因型患者则容易进展为慢性乙型肝炎甚至肝硬化。     

白细胞介素-2基因多态性与慢性乙型肝炎的相关性

目的 探讨白细胞介素-2(IL-2)基因多态性与慢性乙型肝炎的相关性,以及对HBVDNA水平的影响.方法 应用聚合酶链反应-限制性片段长度多态性分析和DNA测序的方法检测155例慢性乙型肝炎患者和170名健康对照者的IL-2基因-385T/G、+114T/G单核苷酸多态性位点基因型,血清HBV DNA测定采用荧光定量PCR技术.结果 IL-2基因+114T/G多态性在慢性乙型肝炎组和正常人群中的频率分布差异无统计学意义.IL-2基因-385T/G多态性在两组人群中的频率分布差异有统计学意义,X2=7.377,P<0.05.等位基因频率的相对风险分析发现,G等位基因携带者患慢性乙型肝炎的风险是T等位基因的1.490倍(OR=1.490,95%CI:1.085-2.046);进一步比较慢性乙型肝炎患者IL一2基因多态性与HBV DNA复制的关系,发现高水平HBVDNA(≥1×10<'3>拷贝/ml)组-385G等位基因携带者分布频率明显高于低水平HBV DNA组(<1×10<'3>拷贝/ml),X2=6.051,P=0.014,差异有统计学意义.结论 IL-2基因-385T/G多态性可能与HBV具有相关性,其中G等位基因可能是慢性乙型肝炎的遗传易感基因,携带G等位基因的个体可能更利于HBV DNA的复制.     

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.