乙型肝炎病毒特异性T细胞治疗慢性乙型肝炎的临床研究

据62例慢性乙型肝炎分组治疗观察,治疗组HBV DNA阴转率33.3％,对照组为11.1％,HBeAg阴转率和抗-HBe阳转率分别为44.4％和33.3％,对照组分别为13.3％和10.0％。治疗结束后半年随访HBV DNA、HBeAg阴转率和抗-HBe阳转率分别为50.0％、55.6％和44.4％。故认为HBV特异性细胞毒T淋巴细胞治疗,对慢性乙型肝炎可获满意临床效果。     

拉米夫定治疗慢性乙型肝炎90例

目的:观察拉米夫定对血清HBsAg、HBeAg、HBV DNA阳性的慢性乙型肝炎患者的疗效。方法:180例HBsAg、HBeAg、HBV DNA阳性的慢性乙型肝炎患者随机分成对照组(90例)和治疗组(90例)。对照组采用一般保肝、降酶综合治疗;治疗组在对照组综合治疗基础上每日口服拉米夫定100mg,疗程1年。结果:对照组、治疗组患者ALT复常率分别为77例(85.6％)、79例(87.8％),两组差异无显著性意义(P>0.05)。对照组7例(7.8％)血清HBV DNA阴转,5例(5.6％)血清HBeAg阴转,2例(2.2％)出现HBeAg/抗-HBe血清转换;治疗组78例(86.7％)血清HBV DNA阴转,64例(71.1％)血清HBeAg阴转,44例(48.9％)出现HBeAg/抗-HBe血清转换;两组差异有非常显著性意义(P<0.005～P<0.001)。结论:拉米夫定能有效抑制HBV DNA复制,促使患者HBeAg转阴、HBBeAg/抗-HBe血清转换;但也有部分病例治疗无效和出现YMDD病毒变异。     

替比夫定联合胸腺五肽治疗HBeAg阳性慢性乙型肝炎的疗效观察

目的探讨替比夫定联合胸腺五肽治疗HBeAg阳性慢性乙型肝炎的疗效。方法91例慢性乙型肝炎患者接受替比夫定联合胸腺五肽治疗,90例单服替比夫定,观察治疗48周时的疗效。结果两组患者HBV子DNA阴转率相近,但联合治疗组HBeAg阴转45例（49．5％）,HBeAg／抗-HBe血清转换31例（34．1％）,明显高于单药治疗组（分别为32．2％和21．1％）。结论替比夫定联合胸腺五肽治疗HBeAg阳性慢性乙型肝炎能提高HBeAg阴转和HBeAg／抗-HBe血清转换率。     

阿德福韦酯治疗HBeAg阴性慢性乙型肝炎22例临床观察

目的观察阿德福韦酯治疗HBeAg阴性慢性乙型肝炎的疗效。方法46例HBeAg阴性慢性乙型肝炎患者被随机分成阿德福韦酯组和拉米夫定组，阿德福韦酯组予阿德福韦酯10mg口服，1次／日；拉米夫定组予拉米夫定100mg口服，1次／日，治疗观察18个月。结果治疗6月、12月、18月时阿德福韦酯组HBV DNA阴转率分别为54．5％、63．6％、77．3％，肝功能复常率分别为50％、59．1％、72．7％；拉米夫定组治疗6月、12月、18月时HBV DNA阴转率分别为75％、66．7％、54．1％，肝功能复常率分别为62．5％、66．7％、54．1％，两组治疗6月和18月时HBV DNA阴转率、肝功能复常率比较都有显著性差异（P〈0．05）。结论阿德福韦酯治疗HBeAg阴性慢性乙型肝炎有较好的抗病毒疗效，安全性良好。     

干扰素α-1b联合其他抗病毒药物治疗慢性乙型肝炎的疗效比较

目的观察比较干扰素α-1b及联合拉米夫定、胸腺肽、苦参素治疗慢性乙型肝炎的疗效?方法将86例慢性乙型肝炎患者随机分成四组，采用干扰素α-1b及干扰素α-1b分别联合拉米夫定、胸腺肽、苦参素抗病毒治疗，随访至18个月，观察肝功能及乙型肝炎病毒标记物、HBV DNA变化情况。结果四组病例肝功能均恢复较好，18个月时HBV DNA阴转率分别为45％、45．5％、50％和75％，HBeAg阴转率分别为40．5％、40．9％、60％和62．5％，HBeAg／抗-HBe血清转换率分别为30％、31．8％、45．0％和45．8%。结论干扰素α-1b治疗慢性乙型肝炎有一定疗效，联合其他抗病毒药物后疗效有一定提高，但无统计学差异。     

中药益肝丸治疗慢性乙型肝炎临床研究

应用益肝丸治疗慢性乙型肝炎3个月,ALT下降均值为230U/L;复常率为82.0％;HBsAg下降均值(p/n)为3.3,阴转率为32％;HBeAg下降均值为3.0,阴转率为54％;HBV DNA阴转率为53.8％;抗-HBs阳转率为23.9％,抗HBs上升均值为0.62(p/n)值。说明益肝在降ALT,HBsAg、HBeAg、HBV DNA阴转及抗-HBs阳转方面有明显疗效。同时经疗效4级判定与分析,益肝丸治疗组有效率为94％,其中近期临床基本治愈率为40％,显效率为24％,好转率为32％。     

苦参素治疗慢性乙型肝炎的临床研究

目的探讨苦参素治疗慢性乙型肝炎的疗效,寻找治疗慢性乙型肝炎的有效方法. 方法采用多中心的开放、对照研究,治疗分4组,分别为苦参素、苦参素联合单磷酸阿糖腺苷、干扰素α1b及葡萄糖组,共治疗慢性乙型肝炎患者196例,观察ALT、AST 及病毒标志物的变化. 结果治疗结束时,苦参素组、苦参素与单磷酸阿糖腺苷联合治疗组及干扰素组的HBV DNA、HBeAg阴转率、抗-HBe的阳转率及ALT的复常率均较葡萄糖组高,4组HBV DNA的阴转率分别为42.3%、55.8%、40.7%和2.1%(P＜0.01),HBeAg阴转率分别为36.5%、39.5%、38.9%和10.6%(P＜0.05);抗-HBe的阳转率分别为25%、30.2%、25.9%和6.4%(P＜0.05).ALT的复常率分别为36.5%、41.9%、27.8%和8.5%(P＜0.05).随访12个月,HBV DNA和HBeAg的阴转率及抗-HBe的阳转率在苦参素组、联合治疗组和干扰素组差异无显著性(P＞0.05).总有效率分别为40.8%、60.8%和43.1%. 结论苦参素或苦参素联合单磷酸阿糖腺苷治疗慢性乙型肝炎有较好的HBV DNA及HBeAg阴转率和抗-HBe的阳转率,其远期抗病毒疗效与干扰素相似.     

监测核苷(酸)类抗HBV药物治疗CHB的停药指标

抗HBV感染的治疗难点之一是安全停药或治疗终点的确定,目前主要依靠血清HBV DNA、HBeAg/抗-HBe、HBsAg/抗-HBs和抗-HBc评估慢性乙型肝炎治疗效果,并以持久的HBsAg清除作为停药标准。但血清HBsAg阴转率很低且难以实现"临床治愈(或功能性治愈)",因此,近年来提出了许多新的指导慢性乙型肝炎患者停药的指标,如肝组织HBV ccc DNA、血清HBcrAg和血清HBV RNA。本文就以上指标的研究进展进行综述。     

拉米夫定联合胸腺肽治疗慢性乙型肝炎的疗效观察

目的 评价拉米夫定联合胸腺肽治疗慢性乙型肝炎(CHB)的近、远期疗效和安全性，探讨两者联合治疗的协同作用。方法 将207例HBV DNA及HBeAg阳性的CHB患者随机分为甲乙两组，甲组采用拉米夫定和胸腺肽联合治疗，乙组单用拉米夫定治疗。胸腺肽15mg口服，每日1次，疗程6个月。两组拉米夫定治疗均为100mg，每日1次，口服，其中甲组92例(92／124)、乙组70例(70／83)用药超过12个月。两组在治疗6个月、12个月时分别进行疗效评价，治疗结束后继续随访12个月。结果 治疗6个月时，甲乙两组ALT复常率分别为87．1％和74．7％，甲组显著高于乙组(P＜0．05)，但两组HBV DNA阴转率、HBeAg阴转率及HBeAg／抗—HBe血清转换率均无显著性差异(P＞0．05)。治疗12个月时，甲乙两组ALT复常率和HBV DNA阴转率无显著性差异(P＞0．05)，甲组HBeAg阴转率及HBeAg／抗-HBe血清转换率均显著高于乙组(P＜0．05)。随访结束时，甲组从量复常率、HBV DNA阴转率、HBeAg阴转率及HBeAg／抗—HBe血清转换率均显著高于乙组(P＜0．05)。结论 拉米夫定与胸腺肽联合治疗CHB，疗效明显优于单用拉米夫定，是CHB患者安全有效的治疗方法。     

珠子肝泰治疗慢性乙型肝炎的免疫组织化学研究

目的：观察珠子肝泰对慢性乙型肝炎患者肝组织内HBsAg和HBcAg的影响。方法：对21例慢性乙型肝炎应用珠子肝泰进行治疗，3次／d，每次4粒（0．8g)，疗程6个月。 在治疗开始前和疗程结束后采集血清和肝细胞标本，进行血清学、病理学和免疫组织化学检查。结果：治疗后、血清内HBeAg和HBV DNA的转阴率分别为45．0％和47．4％，81％的患者肝组织损伤改善或修复，45．4％的患者肝纤维化程度减轻，肝内HBsAg和HBcAg的转阴率分别为19．0％和23．8％。结论：珠子肝泰在抑制慢性乙型肝炎患者血清HBV复制标志和改善肝组织病理损伤程度的同时，对肝细胞内乙肝病毒感染因子也有一定抑制作用。     

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.