新型乙型肝炎核酸疫苗pVAX1-C3d-S2S的免疫预防效应

既往的乙型肝炎（乙肝）血源疫苗和目前使用的基因工程多肽疫苗已在很大程度上控制了乙肝的流行。众多研究表明，接种乙肝核酸疫苗后能长时间诱导特异性抗体的产生和较强的细胞毒T淋巴细胞（CTL）应答，有望用于HBV感染的预防和治疗。但目前仍存在一些问题，如血源疫苗的安全性，现有基因工程多肽疫苗的部分接种者无应答，以及所诱导的免疫应答效率偏低等。     

乙肝疫苗免疫应答与主要组只相容性抗原(MHC)表达关系的研究进展

有资料表明，全球约有3．5亿乙肝病毒携带者和慢性乙型肝炎患者。约25％的乙肝病毒感染者死于与之相关的肝病和肝癌。自1981年乙肝疫苗获准使用后，乙肝感染率较之前明显下降。疫苗的免疫原性、保护性、安全性获得一致认可。但约5％-10％的健康人在按照标准方案实施一个免疫程序的乙肝疫苗接种后，乙肝表面抗体的滴度达不到保护水平（〈10mIU／ml），称为无／低应答者（抗-HBs水平低于2mIU／ml为无应答，低于10mIU／ml为低应答）。健康人群中即使控制了疫苗接种的外部因素（疫苗抗原含量。注射途径，部位等），机体的一般因素（年龄，性别，体重等）和其他因素（如病毒变异）。     

乙肝疫苗的安全性——在疫苗制造的常规过程中灭活爱滋病病毒

直至最近以前仍无法在体外生产乙肝抗原,只能用乙肝携带者的血清制备疫苗。在美国,一种新疫苗(Hepatavax-B)已获准使用,已证明该疫苗具有高效和易予被人们耐受的特点,并已推广用于乙肝感染的     

广州市国产冻干无佐剂狂犬病疫苗使用人群狂犬病毒抗体检测情况

目的了锯注射国产冻干无佐剂狂犬病疫苗使用后的免疫效果并与非冻干狂犬病疫苗比较。方法一部分冻干国产无佐剂狂犬病疫苗受免者与非冻干疫苗受免者一样在5针全程免疫后第14天抽血并采用免疫酶联吸附法检查狂犬病毒抗体阳转情况，另一部分则在注射完第4针后即进行检查，之后比较检查结果。结果使用国产冻干无佐剂狂犬病疫苗受免者抗体阳转率为96．13％（794／826），而使用非冻干狂犬病疫苗受免者狂犬病毒抗体阳转率为89．84％（115／128），经X^2检验，两者差异有非常显著性（P〈0．01）。此外使用冻干狂犬病疫苗受免者在5针全程免疫后过15天进行检查其狂犬病毒抗体阳转率为98．90％（179／181），与在注射完第4针后即进行检查的抗体阳转率79．14％（645／815）相比较，经X^2检验其差异也有显著性（P〈0．05）。结论本文资料说明国产冻干无佐剂狂犬病疫苗较之非冻干疫苗更有效，其5针全程免疫后过15天检查狂犬病毒抗体阳转率可达98％～100％，而且符合卫生部的要求不含AL（OH）辅助剂。     

治疗性乙型肝炎疫苗研究进展

自1982年预防性乙型肝炎（乙肝）疫苗问世以来,已有数以亿计的人使用过乙肝疫苗,其保护率达90％～95％,为人们提供了抗HBV感染的利器。     

乙肝疫苗的不良反应

经世界各地学者的反复实践证明，乙肝（HB）疫苗可使90％接种者产生保护性抗体（抗一HBS），具有卓越的免疫效能，对阻断乙肝病毒的传播及防治继发症（慢性肝炎、肝硬化和肝癌）起决定性作用。因此，应用日渐广泛。为方便临床用药，本文就HB疫苗的不良反应做一综述。一、HB疫苗引起人体的皮肤反应Nagafuchis等‘”曾报道灭活HB疫苗可引起人体对HBSAg发生迟发型超敏性皮肤反应（DTH）：药品每瓶含176ug冻干HBSAg和880卜g铝盐，用磷酸盐缓冲液溶解至50卜g／ml，用此液注射干受试者前臂皮内。在抗一HBS阳性成人中24～48／J’时均可…     

乙型肝炎疫苗的不良反应

乙型肝炎(乙肝)疫苗是预防并最终控制乙肝病毒复制的有效手段.目前,全球已有150个国家将乙肝疫苗纳入计划免疫.乙肝血源疫苗(PDV)于1981年被正式批准使用;重组酵母乙肝疫苗(YDV)于1986年被获准使用.我国于1992年批准乙肝中国仓鼠卵母细胞(CHO)重组疫苗试生产,1996年正式生产.这些疫苗对控制乙肝同样有效,免疫应答均在90%以上.由于乙肝血源疫苗有一定的潜在危险性,且我国乙肝基因重组疫苗的生产量已能满足需要.因此,卫生部决定于2000年起停止使用乙肝血源疫苗.     

HBsAg蛋白疫苗对HBV感染免疫耐受患者的治疗作用

目的：探索乙肝治疗性疫苗（即HBsAg蛋白疫苗，由乙肝疫苗60μg、卡介苗素1mg、花生油水乳化剂0．1ml组成，混合使用），对慢性乙型肝炎免疫耐受患者的治疗效果。方法：选择120例HBsAg＋、HBeAg＋、抗-HBc＋、HBVDNA＋，ALT、AST正常者，垂直传播、水平传播各半，分3组：治疗1组（垂直传播）40例，治疗2组（水平传播）40例，对照组（水平垂直各半）40例。给药方法：HBsAg蛋白疫苗每3周双侧三角肌注射1次共12个月，HBIG 200IU每3周1针肌注，共12个月。结果：治疗1组：HBeAg转阴率为50％，HBVDNA阴转率为57．5％；治疗2组：HBeAg阴转率50％，HBVDNA阴转率57．5％；对照组HBeAg转阴率为5％，HBVDNA阴转率为20％。结论：HBsAg蛋白疫苗对慢性乙型肝炎免疫耐受有较好的治疗作用，可进一步研究试用。     

乙肝病毒母婴传播及预防的研究现状

病毒性肝炎是一种发病率高、感染力强，严重危害人类健康的传染病。其中以乙型肝炎（乙肝）危害性最大。我国是乙肝（HBV）高发区，乙肝病毒在人群中的感染率高达60%乙肝表面抗原（HBsAg）携带率亦高达10％～15％，且30％～50％是母婴传播所造成，它不仅造成人群中众多的HBsAg携带者，而且是引起成人慢性肝炎、肝硬化以及肝癌的重要因素。因此各国学者对其作了大量的研究工作并获得重大进展，现将近年来对母婴传播及预防的进展综述如下：     

浓缩人用狂犬病疫苗致过敏反应22例

我站１９９６年３月～１９９７年４月对被犬等动物咬伤者１５００例用浓缩人用狂犬病疫苗进行预防接种，至今无一例发病死亡，其中２２例接种后发生不同程度的过敏反应（占１．４６％），现报告如下。１疫苗来源及使用方法我站使用卫生部成都生物制品研究所生产的浓缩人用...     

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.