聚乙二醇干扰素α-2a治疗慢性丙型肝炎病毒／乙型肝炎病毒共感染临床疗效

目的研究慢性丙型肝炎（CHC）与丙型肝炎病毒/乙型肝炎病毒（HCV/HBV）共感染者用聚乙二醇干扰素α-2a（PEG-IFNα-2a）抗病毒治疗疗效的观察。方法治疗前后定期采集31例CHC、30例HCV/HBV共感染者的外周血,检测HCV RNA、HBV DNA和肝脏纤维化指标。结果治疗后CHC患者血清中HCV RNA含量51.6%〈102拷贝/ml,HCV/HBV共感染者HCV、HBV下降均不理想。结论 PEG-IFNα-2a抗病毒治疗HCV/HBV共感染者疗效较单纯丙型肝炎患者差,但对HBV、HCV有抑制作用,并部分改善机体免疫功能及肝功能。     

慢性丙型肝炎患者Ⅰ型干扰素受体启动子基因多态性与抗病毒疗效的关系

目的研究慢性丙型肝炎(CHC)患者Ⅰ型干扰素受体之一IFNAR1启动子基因的单核苷酸多态性与干扰素(IFN)α抗HCV疗效的关系。方法应用聚乙二醇干扰素α联合利巴韦林抗HCV治疗,根据抗病毒疗效将73例患者分为应答组与无应答组,并对其IFNAR1启动子基因进行扩增及测序。结果 73例患者中应答组47例,无应答组26例,在-568、-408、-77、-3位点发现基因多态性,共10种基因单体型,其中单体型-568C/-408C/-77(GT)5/-3C和-568C/-408T/-77(GT)5/-3T出现频率最高。非-568C/-408C/-77(GT)5/-3C者的抗病毒应答率77.1%高于-568C/-408C/-77(GT)5/-3C者52.6%,(χ2=4.773,P=0.029),-568C/-408T/-77(GT)5/-3T者的抗病毒应答率90.9%高于非-568C/-408T/-77(GT)5/-3T者59.7%,(χ2=3.92,P=0.048)。结论 CHC患者IFNAR1启动子基因多态性可能影响IFNα抗HCV治疗应答。     

慢性丙型肝炎患者外周血若干细胞免疫的评价及意义分析

目的　探讨丙型肝炎病毒 (HCV)感染慢性化的原因及免疫发病机制。方法　对慢性丙型肝炎 (CHC)患者外周血CD3、CD4、CD8及自然杀伤 (NK)细胞数、细胞趋化因子受体 6 (CCR6 )、干扰素 γ受体 (IFN γRα)用流式细胞仪进行了检测 ,用酶联免疫吸附 (ELISA)法检测外周血Th1、Th2类细胞因子IFN γ、IL 10 ,并对它们之间的相互关系进行了分析。结果　CHC患者外周血中T淋巴细胞总数、CD4、CD8及NK细胞数均显著下降 ;IFN γRα的表达降低 ,IFN γ、IL 10浓度及IFN γ/IL 10 (Th1/Th2 )比例均显著低于对照组 ,以IFN γ的下降尤为明显 ,但CCR6的表达较对照组明显升高。结论　CHC外周T淋巴细胞、NK细胞数量减少 ,淋巴细胞表面IFN γRα表达降低、血清IFN γ、IL 10水平及IFN γ/IL 10比例均下降 ,存在Th1/Th2比例倒置 ,这可能是CHC患者机体免疫功能低下 ,引起病毒持续感染的原因之一 ;同时CHC患者CCR6表达增高 ,可介导部分激活的效应性T细胞向肝脏内迁移 ,参与局部免疫反应 ,这可能是CHC重要发病机制。     

丙型肝炎病毒感染及抗病毒治疗对甲状腺的影响

丙型肝炎病毒（HCV）是慢性肝炎、肝硬化、肝细胞癌的主要原因。多种肝外疾病都和HCV慢性感染有关系,并且在慢性HCV感染的患者中甲状腺失调是很普遍的。干扰素（IFN）联合利巴韦林（RBV）被公认为是治疗慢性丙型肝炎患者有效的方案,然而,甲状腺功能紊乱也是IFN抗病毒治疗的一个副作用。本综述包含了HCV慢性感染直接对甲状腺的影响和IFNα联合RBV抗病毒治疗所诱发的甲状腺功能紊乱及自身抗体的变化。     

脂质过氧化物酶体增殖物激活受体在脂质方面的研究进展

脂质过氧化物酶体增殖物激活受体(PPAR)存在PPARα、PPARδ(也称PPARβ)和PPARγ三种亚型,本文简述各型在脂肪细胞分化和脂质代谢中的重要作用。PPAR激动剂对脂质代谢紊乱性疾病具有重要的临床价值。     

干扰素治疗小儿慢性丙型肝炎综述

HCV(C型肝炎病毒)感染后,50％～80％以上的病人发展成慢性肝炎,其中20％发展为肝硬变,部分病人最终发展为肝细胞癌,危害极大。近年来,多数随机对照研究证实,干扰素(IFN)治疗慢性丙型肝炎(CHC)可清除病毒,有效抑制疾病的活动性,多数患者病情可缓解。α-IFN已成为CHC治疗的首选药物,但其治疗小儿HCV感染的结果较少见报道,从已获得的资料表明,小儿的治疗反应比     

过氧化物酶增殖物激活受体α与脂质代谢

血脂质异常的重要性已众所周知,其发生机制尚未完全阐明。随着过氧化物酶增殖物激活受体(PPAR)的发现,PPARα与脂质代谢的关系日益受到关注。本文对有关文献进行综述。一、PPAR的结构PPAR 是配体活化的受体超家族,包括三种亚型即PPARα、PPARγ和 PPARβ/δ。PPAR 具有 DNA     

冷球蛋白血症对丙型肝炎患者病毒学应答的影响

目的 探讨在应用聚乙二醇干扰素α-2a联合利巴韦林抗病毒治疗的慢性丙型肝炎(CHC)患者中,冷球蛋白血症对抗病毒治疗效果的影响. 方法 40例接受聚乙二醇干扰素α-2a联合利巴韦林抗病毒治疗的CHC患者进入研究,检测HCV基因型与基线、用药后4周、12周及治疗结束后24周患者血清HCV RNA水平,并检测基线患者血清中的冷球蛋白.连续型变量用独立样本t检验或秩和检验,分类资料用x2检验或Fisher' s精确概率法,对抗病毒治疗效果相关影响因素的分析用多元logistic回归分析.结果 治疗4周后快速病毒学应答发生率在冷球蛋白阳性患者(6/18,33.3％)低于阴性患者(15/22,68.2％,P=0.028).冷球蛋白阳性患者的持续病毒学应答发生率也低于阴性患者(0对比6/6,P=0.012).结论 冷球蛋白阳性的CHC患者快速病毒学及持续病毒学应答疗效低于冷球蛋白阴性的CHC患者.     

高糖对HDL调节THP-1巨噬细胞CD36和过氧化体增殖物激活型受体γ表达的影响

目的　观察高糖对　HDL调节THP-1巨噬细胞清道夫受体CD36和过氧化体增殖物激活型受体γ（PPARγ）表达的影响。方法　用50　mg/L　ox-LDL、50　mg/L　ox-LDL+50　mg/L　HDL、50　mg/L　ox-LDL+50　mg/L　HDL+20　mmol/L　D-葡萄糖、50　mg/L　HDL、50　mg/L　HDL+20　mmol/L　D-葡萄糖孵育THP-1巨噬细胞24　h,采用油红O染色观察细胞内脂质蓄积情况,　RT-PCR和Western　Blot分别检测CD36、PPARγ、p-PPARγ　mRNA和蛋白的表达。结果　加用HDL组明显减少脂质蓄积,加用HDL组的CD36　mRNA　和蛋白的表达下调,PPARγ的mRNA　和蛋白及p-PPARγ的蛋白表达上调;而同时加用50　mg/L　HDL和　20　mmol/L葡萄糖组CD36和PPARγ的mRNA及蛋白表达上调,而p-PPARγ的表达下调（P<0.05）,并促进脂质蓄积。结论　高糖可使HDL　抑制CD36表达及脂质蓄积的作用减弱。     

合并慢性乙型肝炎病毒感染对登革病毒1型急性感染者免疫应答和临床的影响

目的 了解合并慢性HBV感染对急性登革病毒感染引起的免疫应答和临床的影响.方法 采用ELISA法同时检测了310例登革病毒1型感染患者血清中IFNα、IFNβ、IFNγ、IL-10和TNFα等细胞因子水平,其中8％(25/310)合并感染了HBV,对照组的血清标本取自41名健康者和47例慢性HBV感染患者.多组比较采用单因素方差分析,检测指标的相关性分析采用Spearman等级相关检验.结果 在急性登革病毒感染期间,IFNα分泌水平显著高于IFNβ,分别为(95.1±279.3) pg/mL和(2.8土16.2)pg/mL,但在合并HBV感染的患者中IFNα的分泌明显减少,为(86.5±358.1) pg/mL;分别在发热第2天、第3～4天和第6天,IFNα、IFNβ及IL-10的中位数达到峰值.在单纯登革病毒感染的患者中,IFNα水平与血小板计数和血清ALT水平呈负相关(分别为r=-0.2327,-0.2122,均P＜0.01).结论 合并慢性HBV感染可以改变急性登革病毒感染引起的免疫反应;IFNα的分泌可能与出血倾向相关,但对肝脏的炎性损伤可能起保护作用.     

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.     

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.     

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.     

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.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.