对熊去氧胆酸不完全应答的原发性胆汁性肝硬化患者应用熊去氧胆酸联合非诺贝特可改善预后

正【据《Aliment Pharmacol Ther》2016年1月报道】题:对熊去氧胆酸不完全应答的原发性胆汁性肝硬化患者应用熊去氧胆酸联合非诺贝特可改善预后(作者Cheung AC等)贝特类似乎能够改善原发性胆汁性肝硬化(PBC)患者的生化指标,但是哪些因素可以预测应答以及治疗是否可以提高无肝移植的生存率仍不清楚。来自加拿大的Cheung等在一家三级医疗中心进行了一项回顾性队列研究。评估熊去氧胆酸(UDCA)不     

原发性胆汁性肝硬化41例临床病例分析

目的 分析原发性胆汁性肝硬化(PBC)患者的临床特征,提高对该病的认识.方法 回顾性分析41例原发性胆汁性肝硬化患者患者的临床特征、生化指标和组织学特点以及熊去氧胆酸的治疗反应.结果 41例原发性胆汁性肝硬化患者中女性与男性之比为9:1,主要临床表现为皮肤瘙痒、乏力、纳差和黄疸,所有患者碱性磷酸酶(ALP)与γ-谷氨酰转肽酶(GGT)均明显升高.40例(97.6%)患者的抗线粒体抗体(AMA)及AMA-M2亚型抗体阳性.共有24例患者行肝穿刺病理检查,早期(Ⅰ、Ⅱ期)占83.3%,晚期(Ⅲ、Ⅳ期)占16.7%.41例患者经过熊去氧胆酸(UDCA)治疗6月后,生化指标较治疗前均有明显改善.结论 PBC主要累及中年女性,其特征为碱性磷酸酶与γ-谷氨酰转肽酶升高和AMA及M2亚型阳性,熊去氧胆酸治疗能有效改善肝功能.     

原发性胆汁性肝硬化肝移植术后复发的研究进展

原发性胆汁胜肝硬化（primary biliary cirrhosis，PBC）是一种缓慢的进行性自身免疫性肝脏疾病，其组织病理学主要表现为门脉区炎症和免疫介导的肝内胆管破坏，进而引起胆汁分泌减少和代谢过程中的有毒物质在肝脏蓄积，最终导致肝脏损伤、肝纤维化、肝硬化，直至肝功能衰竭。目前治疗PBC最有效的药物是熊去氧胆酸（ursodeoxycholic acid，UDCA），它能有效改善患者肝功能，早期患者及早并长期应用UDCA可能延缓肝脏组织学进展，但不能改善乏力和瘙痒等临床症状，也无足够证据支持UDCA能延长患者的生存期。     

加味茵陈蒿汤联合熊去氧胆酸治疗原发性胆汁性肝硬化的临床研究

目的:观察加味茵陈蒿汤联合熊去氧胆酸治疗30例原发性胆汁性肝硬化临床分期为早中期患者的临床疗效。方法:60例患者随机分为对照组和治疗组各30例。两组均给予基础治疗,对照组患者同时口服熊去氧胆酸胶囊15～20mg.kg-1.d-1;治疗组患者在对照组基础上加服加味茵陈蒿汤,1剂/d,疗程均为24周。观察治疗前后两组患者的临床疗效、肝功能(γ-GT、ALP、ALT、AST、TBil)、免疫指标(IgM、IgG及IgA)的变化。结果:治疗结束时,治疗组26例(86.7%)患者得到完全反应,与对照组19例(63.3%)比较差异有显著性意义(P<0.05);两组患者治疗后肝功能(γ-GT、ALP、ALT、AST、TBil)均较治疗前明显下降(P<0.05),治疗组治疗后肝功能下降明显优于对照组(P<0.05或P<0.01);治疗后两组患者免疫指标IgM、IgG、IgA均较前有所下降,经比较差异无统计学意义(P>0.05)。结论:加味茵陈蒿汤联合熊去氧胆酸治疗原发性胆汁性肝硬化,较单用熊去氧胆酸疗效更好,并能明显改善患者的肝功能。     

安络化纤丸联合熊去氧胆酸胶囊治疗原发性胆汁性肝硬化疗效观察

目的观察安络化纤丸联合熊去氧胆酸胶囊治疗原发性胆汁性肝硬化患者的疗效。方法随机将64例原发性胆汁性肝硬化患者分为治疗组32例和对照组32例。对照组32例给予甘草酸二胺肠溶胶囊、熊去氧胆酸胶囊(UDCA)治疗,治疗组在对照组基础上加用安络化纤丸,疗程均为三个月。观察治疗前后患者临床症状、体征的变化以及肝功能、肝纤维化、肝脾影像学变化。结果两组患者在治疗过程中均未出现明显不良反应。两组疗效相比,治疗组有效率90.6%,明显高于对照组68.8%(P=0.024);治疗后血清ALT、AST、ALP、GGT水平相比,治疗组较对照组显著减低(a P=0.082,*P=0.0008,#P=0.037);治疗后肝脾影像学变化,治疗组较对照组有显著改善(a P=0.021);结论安络化纤丸与熊去氧胆酸胶囊联合治疗原发性胆汁性肝硬化临床效果明显、不良反应少,可以改善患者临床不适、体征、肝功能、肝纤维化及临床肝脏影像学指标。     

’99上海食管疾病现代治疗暨消化病进展研讨会

原发性胆汁性肝硬化(PBC)是病因尚不明的慢性进行性胆汁淤积性肝病，至今无特效药物。近年发现熊去氧胆酸(UDCA)可改善肝病患者胆汁郁滞和肝组织的炎症，故有人试用于PBC的治疗并取得一定效果。作者就熊去氧胆酸治疗PBC的价值作一介绍。     

熊去氧胆酸联合异甘草酸镁治疗原发性胆汁性肝硬化的近期疗效观察及护理

目的观察原发性胆汁性肝硬化患者采用异甘草酸镁与熊去氧胆酸联合进行治疗的近期效果,并探讨其护理干预措施。方法随机抽取我院2011~2013年收治的42例原发性胆汁性肝硬化患者,根据患者治疗意愿,分成观察组与对照组,对照组采用熊去氧胆酸治疗,观察组采用异甘草酸镁与熊去氧胆酸联合治疗,两组患者均采用针对性的护理措施进行干预。结果观察组总有效率为84.7%,对照组总有效率为66.7%,观察组总有效率显著优于对照组(P0.05);观察组完成治疗后γ-GGT、ALP、AST、ALT、TBIL等临床指标改变情况与对照组相比,改变较为明显,组间数据对比具有统计学差异(P0.05)。结论原发性胆汁性肝硬化患者采用熊去氧胆酸与异甘草酸镁药物联合进行治疗,获得治疗效果较为明显,使患者的肝功能生化指标得到明显改善,值得临床推广。     

熊去氧胆酸（优思弗）治疗原发性胆汁性肝硬化的临床疗效观察

目的探讨熊去氧胆酸（优思弗）在治疗原发性胆汁性肝硬化中的作用。方法选择原发性胆汁性肝硬化患者60例,随机分成治疗组和对照组。所有研究对象在继续行护肝及支持治疗的基础上,治疗组给予优思弗口服。用法用量：按体重每日10 mg/kg。体重60 kg,每日剂量2粒,早晚各1粒;体重80 kg,每日剂量3粒,早、中、晚各1粒;体重100 kg,每日剂量4粒,早、中各1粒,晚2粒。对照组给予熊去氧胆酸片（国产）每日8～10 mg/kg,早晚进餐时分次给予。治疗均为26周。结果全部患者完成26周治疗。治疗组患者肝功能指标中的ALT、GGT、TBil的改善均明显高于对照组（P〈0.01）;治疗组治疗皮肤瘙痒及乏力的有效率明显高于对照组（P〈0.05）。结论与熊去氧胆酸片（国产）相比,优思弗可以快速、有效地改善肝功能各项酶学指标,治疗皮肤瘙痒及乏力的有效率高,可作为原发性胆汁性肝硬化患者的首选药物治疗。     

国产熊去氧胆酸治疗原发性胆汁性肝硬化患者的随访

目的 观察国产熊去氧胆酸对原发性胆汁性肝硬化患者肝功生化指标的影响.方法 选择北京友谊医院经肝穿活检病理学或AMA-M2阳性而确诊的原发性胆汁性肝硬化患者,应用国产熊去氧胆酸(13-15)mg/ks day,分三次口服,定期(每隔3个月)复查肝功.结果 从用药第三个月起,γ-GT、ALP、ALT、AST水平开始明显下降(P＜0.05).结论 国产熊去氧胆酸可以改善原发性胆汁性肝硬化患者胆汁淤积相关指标(GGT、ALP),降低转氨酶(ALT、AST)水平.     

滋水涵木利胆方联合熊去氧胆酸胶囊治疗原发性胆汁性胆管炎临床研究

目的:观察滋水涵木利胆方联合熊去氧胆酸胶囊治疗原发性胆汁性胆管炎的临床疗效。方法:重庆市中医院肝病科门诊就医的原发性胆汁性胆管炎患者76例,随机分为试验组与对照组,试验组患者采用滋水涵木利胆方联合熊去氧胆酸胶囊治疗,对照组患者单用熊去氧胆酸胶囊,疗程24周,比较2组患者治疗前后中医证候评分、生化指标、肝纤维化、免疫球蛋白IgM、血清胆固醇水平。结果:治疗24周时,与对照组比较,试验组患者中医证候积分明显降低、生化指标(ALT、GGT、ALP)显著改善、肝纤维化指标(HA、CIV)明显下降、血清IgM和总胆固醇水平显著降低,差异均有统计学意义(P<0.05)。结论:滋水涵木利胆方联合熊去氧胆酸胶囊治疗原发性胆汁性胆管炎患者,其疗效优于单用熊去氧胆酸胶囊,可在临床推广应用。     

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.     

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.     

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.