替诺福韦酯单独与联合恩替卡韦挽救治疗恩替卡韦治疗拉米夫定经治慢性乙型肝炎失败患者疗效比较

目的比较替诺福韦酯单药与联合恩替卡韦对恩替卡韦治疗慢性乙型肝炎拉米夫定经治患者仍应答不佳或发生病毒学突破的挽救方案的临床疗效及安全性。方法将80例恩替卡韦序贯治疗仍效果欠佳的拉米夫定经治慢性乙型肝炎患者随机分为单药组40例和联合组40例。单药组给予替诺福韦酯(300 mg/d)替换治疗;联合组使用替诺福韦酯(300 mg/d)和恩替卡韦(0.5 mg/d)治疗。所有患者均治疗48周,检测基线,治疗12、24和48周时病毒学、生化学、血清学指标。比较两组患者上述治疗时间点的完全病毒学应答率、ALT复常率、病毒学突破率和HBeAg血清学转换率及观察药物不良反应。结果单药组患者治疗48周后完全病毒学应答率、ALT复常率、病毒学突破率、HBeAg血清学转换率分别为85.0%(34/40)、76.2%(16/21)、0、13.1%(3/23),联合组分别为87.5%(35/40)、77.3%(17/22)、0、16.0%(41/25),两组比较差异无统计学意义(均P0.05)。两组患者耐受性均良好,无一例出现严重不良反应而导致停药。结论对于恩替卡序贯治疗后仍应答不佳或发生病毒学突破的拉米夫定经治慢性乙型肝炎患者,替诺福韦酯单药替换恩替卡韦的挽救治疗仍能有效抑制HBV DNA复制,是一种行之有效的优化治疗方案。     

序贯聚乙二醇干扰素α-2a治疗恩替卡韦经治未达满意终点乙型肝炎的疗效

目的 评估序贯聚乙二醇干扰素(Peg-IFN)α-2a治疗恩替卡韦经治HBeAg阳性慢性乙型肝炎的疗效与安全性.方法 57例恩替卡韦治疗96周达到HBV DNA＜500拷贝/ml且0.227PEIU/ml＜HBeAg≤50.000 PEIU/ml的HBeAg阳性慢性乙型肝炎患者,27例接受ETV与PegIFN α-2a联合治疗12周后改为Peg-IFN α-2a单药治疗至48周(试验组),30例继续接受恩替卡韦治疗48周(对照组),分别在治疗的24、48周进行生物化学、病毒学、血清学评估.统计学处理用t检验或x2检验.结果 试验组与对照组基线ALT、HBsAg、HBeAg水平有可比性.治疗48周,试验组HBeAg阴转率与HBeAg血清学转换率分别为40.7％和37.0％,与对照组的16.7％和13.3％相比,差异有统计学意义(x2值分别为4.079和5.11,P值均＜0.05).试验组HBsAg清除率和HBV DNA反弹率分别7.4％与11.1％,对照组无HBsAg清除和HBV DNA反弹(x2值分别为2.307 和3.519,P值均＞0.05).治疗48周,试验组HBsAg水平明显低于对照组[(2866.0±2580.4)IU/ml对比(4335.8±2650.0) IU/ml,t=5.11,P＜0.05]. 结论 恩替卡韦经治的HBeAg阳性慢性乙型肝炎患者,序贯Peg-IFNα-2a治疗有助于实现HBeAg血清转换和HBsAg定量下降.     

恩替卡韦联合双环醇治疗HBeAg阳性慢性乙型肝炎的疗效分析

目的 研究恩替卡韦联合双环醇片治疗HBeAg阳性慢性乙型肝炎患者的疗效和安全性.方法 选择未应用其他抗病毒药物的HBeAg阳性慢性乙型肝炎患者113例,并将其随机分成两组.试验组57例,每日口服恩替卡韦0.5 mg,同时每日服用双环醇片75 mg;对照组56例,仅给予口服恩替卡韦每日0.5 mg,两组均连续用药104周,观察治疗前后血清丙氨酸氨基转移酶(ALT)水平及病毒学指标的改变.结果 两组患者血清ALT均明显下降,试验组更为显著(P＜0.01).治疗12周时,两组患者HBeAg转阴率及血清学转换方面比较,差异均无统计学意义(P＞0.05).随治疗时间延长,在治疗24、52、104周各时间点,试验组HBeAg转阴率及血清学转换均优于对照组,两组比较差异有统计学意义(P＜0.05).两组HBV DNA水平均出现明显下降,但各治疗时间点HBV DNA下降水平及检测不到比率比较,差异无统计学意义(P＞0.05).治疗52周时,试验组和对照组各出现1例和2例耐药,耐药率分别为1.75％和3.57％,两组比较差异无统计学意义(P＞0.05);治疗104周时,试验组耐药1例,对照组耐药3例,耐药率分别为1.75％和5.36％,两组比较差异有统计学意义(P＜0.05).2组患者均未发生与研究药物相关的不良反应.结论 恩替卡韦与双环醇片联合应用治疗HBeAg阳性慢性乙型肝炎,在肝功能及病毒学方面均取得较好疗效且安全.     

替比夫定和恩替卡韦治疗HBeAg阳性慢性乙型肝炎患者早期疗效分析

目的比较替比夫定与恩替卡韦治疗HBeAg阳性慢性乙型肝炎患者24周疗效及安全性。方法将60例HBeAg阳性慢性乙型肝炎患者随机分为替比夫定组和恩替卡韦组,比较两组治疗第12周和24周的疗效。结果在治疗12周时,两组患者HBV DNA低于检测水平和ALT复常率相比较,差异无统计学意义（P〉0.05）,替比夫定治疗组HBeAg阴转率和HBeAg血清学转换率高于恩替卡韦组（36.7%对14.3%,26.7%对6.7%,P〈0.05）;在治疗24周时,两组HBV DNA低于检测水平、ALT复常率、HBeAg血清学转换率相比较,差异均无统计学意义（P〉0.05）,而替比夫定组HBeAg阴转率高于恩替卡韦组（P〈0.05）;多因素Logistic回归分析发现仅基线ALT水平高的患者更易出现HBeAg血清学转换。结论替比夫定和恩替卡韦治疗CHB患者疗效相当,但替比夫定治疗患者HBeAg阴转率稍高于恩替卡韦治疗。     

恩替卡韦治疗慢性乙型肝炎临床观察

目的评价恩替卡韦分散片治疗慢性乙型肝炎的抗病毒疗效及安全性。方法 30例慢性乙型肝炎患者口服恩替卡韦分散片,另30例对照组口服恩替卡韦,治疗48周。结果治疗组和对照组在治疗48周时,HBV DNA阴转率、HBeAg转阴率和ALT复常率分别为83.3%对86.6%、43.3%对46.6%和100%对100%（P〉0.05）。结论恩替卡韦分散片在治疗慢性乙型肝炎方面具有显著的抗病毒作用,疗效与恩替卡韦片相当,是一种安全有效的治疗药物。     

恩替卡韦治疗慢性乙型肝炎病毒携带者近期疗效观察

目的 观察恩替卡韦治疗慢性HBV携带者的近期疗效与安全陛,探讨慢性HBV携带者抗病毒治疗的临床意义. 方法 慢性HBV携带者47例,慢性乙型肝炎患者46例,诊断均符合“慢性乙型肝炎防治指南(2010年版)”.两组患者均给予恩替卡韦分散片0.5 mg/d口服治疗,观察两组患者治疗第4、12、24、48周血清学应答率、生物化学应答率与突破率的差异,并观察药物相关不良事件发生率.数据均使用SPSS17.0统计分析软件进行,分别采用t检验和x2检验.结果 第4、12、24、48周完全病毒学应答率:慢性HBV携带者组分别为14.9％、51.1％、76.6％和97.9％;慢性乙型肝炎患者组分别为,17.4％、63.0％、89.1％和100.0％,两组间各时间点比较,差异均无统计学意义.第4、12、24、48周部分病毒学应答率:慢性HBV携带者组分别为42.6％、57.4％、85.0％和100.0％;慢性乙型肝炎患者组分别为47.8％、65.2％、89.1％和100.0％,两组间各时间点比较,差异均无统计学意义.第4、12、24、48周HBeAg阴转率:慢性HBV携带者组分别为0、2.1％、4.3％和8.5％;慢性乙型肝炎患者组分别为4.4％、8.7％、13.0％和21.7％,两组间各时间点比较,差异均无统计学意义.第4、12、24、48周HBeAg血清学转换率:慢陛HBV携带者组分别为0、0、2.1％和6.4％;慢性乙型肝炎患者组分别为0、4.4％、10.9％和17.4％,两组间各时间点比较,差异均无统计学意义.HBsAg阴转率与血清学转换率,两组各观察时段均为0.慢性乙型肝炎患者组第4、12、24、48周ALT复常率分别为26.1％、65.2％、91.3％和97.8％.两组患者均无病毒学突破和生物化学突破病例.两组患者均未观察到肾毒性、骨髓抑制、横纹肌溶解或其他药物相关不良事件.结论 采用恩替卡韦分散片治疗慢性HBV携带者近期疗效好、安全.     

重组人干扰素α-2b和恩替卡韦对HBeAg阳性慢性乙型肝炎患者肝脏生化指标的影响

目的探究与分析重组人干扰素α-2b和恩替卡韦对治疗HBeAg阳性慢性乙型肝炎患者的临床疗效及对肝脏生化指标的影响。方法选取我院自2013年9月至2014年9月收治的90例HBeAg阳性慢性乙型肝炎患者,采取随机数字表法分为重组人干扰素α-2b组与恩替卡韦组,每组各45例,对比两组患者治疗12周、24周及52周血清HBV DNA、HBeAg转阴率、HBeAg转换率、ALT复常率、病毒学突破、病毒学反弹率。结果重组人干扰素α-2b组与恩替卡韦组治疗12周后未检测到HBV DNA、HBeAg转阴率、HBeAg转换率及ALT复常率相比差异均无明显统计学意义,治疗24周后未检测到HBV DNA、HBeAg转换率、ALT复常率、病毒学突破率及病毒反弹率相比差异也均无明显统计学意义(P均0.05),重组人干扰素α-2b组治疗24周后较恩替卡韦组相比,HBeAg转阴率较高(P0.05)。重组人干扰素α-2b组与恩替卡韦组治疗52周后相比,未检测到HBV DNA、HBeAg转阴率、HBeAg转换率、ALT复常率较高,病毒学突破率及病毒反弹率较低(P均0.05)。结论重组人干扰素α-2b相比于恩替卡韦治疗HBeAg阳性慢性乙型肝炎的临床疗效更加显著,临床医生需结合患者个体情况以选择最佳治疗方案。     

恩替卡韦联合聚乙二醇干扰素α-2a治疗难治性慢性乙型肝炎HBeAg血清学转换疗效观察

目的临床观察经恩替卡韦治疗1年至4年后e抗原仍为阳性的难治性慢性乙型肝炎的患者,应用恩替卡韦联合聚乙二醇干扰素(PegIFN)α-2a治疗的疗效和安全性。方法将60例患者分为试验组和对照组,试验组在恩替卡韦治疗的基础上加用PegIFNα-2a抗病毒治疗,对照组继续恩替卡韦抗病毒治疗,分别在12周、24周、48周定量检测两组患者肝功能、HBsAg、HBeAg及HBeAb等变化。结果(PegIFN)α-2a联合恩替卡韦治疗24周时HBeAg血清学转换率为26.7%,48周上升至36.7%,明显高于对照组(P0.05),且HBsAg水平持续下降,差异具有统计学意义(P0.05)。结论恩替卡韦抗病毒治疗后e抗原仍为阳性的慢性乙型肝炎患者,加用聚乙二醇干扰素继续抗病毒治疗,可提高HBeAg血清学转换率,缩短疗程,为最终停药可能提供相关依据。     

恩替卡韦联合苦参素治疗慢性乙型肝炎48周疗效观察

目的：观察恩替卡韦联合苦参素治疗慢性乙型肝炎患者48周的临床疗效。方法选择慢性乙型肝炎患者100例,随机分为两组。治疗组52例应用恩替卡韦片联合苦参素片治疗;对照组48例仅服用恩替卡韦片,观察48周。结果在治疗48周时,联合组患者血清 ALT 复常率、HBeAg 转阴率和 HBV DNA 转阴率分别为80.77%、82.69%和82.67%,均优于对照组的72.92%、58.33%和62.50%,差异均具有统计学意义（P〈0.05）。结论恩替卡韦联合苦参素治疗慢性乙型肝炎具有协同作用,且无不良反应。     

拉米夫定联合阿德福韦酯与换用恩替卡韦单药治疗拉米夫定应答不佳患者的疗效对比

目的 观察分别利用拉米夫定和阿德福韦酯联合治疗与换用恩替卡韦单药治疗拉米夫定应答不佳慢性乙型肝炎患者的临床疗效.方法 80例拉米夫定应答不佳的慢性乙型肝炎患者采用随机数字表法分为联合组和单药组,联合组服用拉米夫定100 mg/d和阿德福韦酯10mg/d;单药组服用恩替卡韦0.5 mg/d,观察两组患者治疗48周时的疗效.结果 治疗48周后,联合组的HBV DNA应答率、HBeAg转换率、ALT复常率分别为90.0％、40.0％和95.0％,远高于单药组的70.0％、15.0％和80.0％,两组比较差异均有统计学意义(P＜0.05).治疗48周后,联合组未出现病毒学突破病例;单药组共有2例患者出现病毒学突破.结论 对于拉米夫定应答不佳的慢性乙型肝炎患者,加用阿德福韦酯联合治疗的疗效优于换用恩替卡韦单药治疗,且可降低病毒耐药的发生率.     

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.     

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.     

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.