重型肝炎肝性脑病患者血清中分子物质的作用及肝细胞生长素治疗机制

重型肝炎肝性脑病患者血清中分子物质的作用及肝细胞生长素治疗机制李智伟，刘沛，王兆荃，董祥家本文作者通过研究中分子物质在重型肝炎肝性脑病患者血清中含量的变化及其对鼠脑Ｎａ＋－Ｋ＋ＡＴＰ酶活性的影响，来探讨其作用机制，同时研究肝细胞生长素治疗前后重型肝炎...     

人工肝联合磷甲酸钠治疗重型肝炎21例

我院于2001年2月至2002年3月应用人工肝联合磷甲酸钠治疗重型肝炎21例,取得较满意疗效,现报告如下。 1 材料与方法 1.1 材料 21例重型肝炎系我院肝科2001年2月至2002年3月的住院患者,其中男18例,女3例,年龄21～59岁;亚急性重型肝炎2例,慢性重型肝炎19例。临床分期:早期10例,中期7例,晚期4例。21例患者中,Ⅱ度肝性脑病3例,Ⅲ度肝性脑病2例,Ⅳ度肝性脑病1例,自发性腹膜炎6例,     

乙型重型肝炎并发症对重型肝炎预后影响的荟萃分析

目的荟萃分析乙型重型肝炎并发症对病人预后的影响,并探讨并发症成为乙型重型肝炎诊断标准的可能。方法检索截止到2009年11月国内公开发表的乙型重型肝炎相关的论文,提取文献中含有预后和并发症数据,包括肝性脑病、肝肾综合征、感染、上消化道出血和腹水,将上述效应量进行异质性检验,荟萃分析其合并后的效应量。结果共检索到2229篇文献通过遴选,最终有8项研究纳入荟萃分析,共包含1771例乙型重型肝炎病例。荟萃分析生存组(好转组)和死亡组中肝性脑病、肝肾综合征、感染、上消化道出血和腹水,均存在明显差异(P0.05)。相对危险度依次肝性脑病、肝肾综合征、上消化道出血、感染和腹水。在荟萃分析中肝性脑病、感染和腹水在8项研究中具有同质性。上消化道出血和肝肾综合征有一定异质性。结论荟萃分析发现肝性脑病、肝肾综合征、感染、上消化道出血和腹水在死亡组和生存组之间有明显差异,肝性脑病、感染和腹水同质增加病人死亡率,考虑作为临床乙型重型肝炎预后判断指标。但由于各并发症发病率未超过半数,故各并发症不能作为乙型重型肝炎诊断标准。     

重型病毒性肝炎临床诊断标准探讨(附565例重型病毒性肝炎的临床主要特点分析)

目的分析重型肝炎的临床特点,重新探讨重型肝炎的临床诊断标准。方法使用SPASS软件和SDAS软件将我院近3年收治的565例重型肝炎患者的临床特点进行分析。结果①发生于急性肝炎的45例,发生于慢性的有明确的肝病史及无明确的肝病史分别为400例及120例。②9例急性重型肝炎,出现肝性脑病7例,均在7天内出现。36例亚急性及520例慢性重型肝炎患者,在12周内达到重型肝炎诊断标准分别为100. 0％及82. 2％。③急性重型肝炎发生的肝性脑病均为首先出现,无1例发生腹水。亚急性重型肝炎及慢性重型肝炎首先出现肝性脑病仅为11. 1％及1. 7％,仅发生腹水分别为5. 6％及3. 5％。④无明确肝病史的120例患者,最后诊断为慢性重型肝炎早、中及晚期分别为17例、31例及72例。结论①重型肝炎依发病基础分为急性重型肝炎(暴发性肝衰竭)、亚急性重型肝炎(亚暴发性肝衰竭)及慢性重型肝炎;②暴发性肝衰竭、亚暴发性肝衰竭的时限分别为14天内、15天至24周(半年);③亚急性重型肝炎分腹水型及脑病型;④亚急性重型肝炎及慢性重型肝炎仍应区分为早期、中期及晚期。     

各型重型肝炎的临床特征及影响其预后的危险因素分析

目的了解各型重型肝炎患者的临床特征以及影响其预后的危险因素。方法应用SPSS10.0软件包,对解放军第三○二医院1995—2005年10年间收治的789例各型重型肝炎的临床特征和影响其预后的危险因素进行分析。结果①各型重型肝炎的预后不同,各组间差异显著,慢加急性肝衰竭和慢性肝衰竭的预后差异显著;②乙型肝炎仍是各型重型肝炎的最主要病因;③年龄、凝血酶原活动度(PTA)、总胆红素(TBIL),肝性脑病、肝肾综合征、自发性细菌性腹膜炎、消化道出血等并发症是影响预后的重要指标;④急性重型肝炎(急重)、亚急性重型肝炎(亚急重)和慢性重型肝炎(慢重)患者肝性脑病发生率分别为78.1%、43.0%和42.5%,急重与后2组相比,差异非常显著。急重、亚急重和慢重患者发生率最高的并发症分别为肝性脑病、腹水。结论①各型重型肝炎包括慢加急性肝衰竭和慢性肝衰竭的预后不同,慢重和急重、亚急重的病因明显不同;②肝性脑病是急重患者最主要的并发症,其发生率明显高于亚急重和慢重,而腹水是亚急重和慢重患者最主要的并发症;③PTA等指标对各型重型肝炎的预后是一个重要的灵敏和特异性指标,在无肝性脑病的患者中尤为重要。     

64例急性重型肝炎患者临床特征及预后因素分析

目的进一步了解急性重型肝炎患者的临床特征。方法回顾性分析64例急性重型肝炎患者的临床资料。结果患者好发年龄段为16～40岁;乙型肝炎病毒感染占34.4%,其次为戊型肝炎病毒感染和病原未明者,均分别约占20%以上。在药物性急性重型肝炎患者中,抗结核药物占首位;肝性脑病的发生率为78.1%,出现肝性脑病的时间为1～30天（9.92±6.52天）,肝性脑病的程度与病死率呈正相关（P〈0.001）;无论在发生肝性脑病时,或在诊断重型肝炎时或在病情最重时,平均凝血酶原时间均在50秒以上,凝血酶原活动度均低于20%;患者腹水发生率为46.9%;患者的病死率与病情最重时PT、WBC及中性粒细胞比例呈正相关,而与PTA、TC呈负相关;患者前三位的并发症分别为肝性脑病、电解质紊乱及脑水肿,而与死亡有关的前三位并发症分别为脑疝、肝肾综合征及脑水肿。结论急性重型肝炎患者的病因正呈多元化倾向,病死率高,治疗困难。     

L-鸟氨酸-L-天门冬氨酸治疗慢性重型肝炎并肝性脑病32例

肝性脑病是重型肝炎常见的严重并发症之一,防治原则是针对其发病机制来采取措施或避免及清除肝性脑病的诱因。我院自1999年11月～2001年4月应用肝病新药:L-鸟氨酸-L-天门冬氨酸(商品名阿波莫斯,德国MERZ制药有限公司生产)治疗慢性重型肝炎并肝性脑病32例,现报告如下。     

重型病毒性肝炎临床诊断标准探讨（附565例重型病毒性肝炎的临床主要特点分

目的 分析重型肝炎的临床特点,重新探讨重型肝炎的临床诊断标准。方法 使用ＳＰＡＳＳ软件和ＳＤＡＳ软件将我院近３年收治的５６５例重型肝炎患者的临床特点进行分析。结果 （１）发生于急性肝炎的４５例,发生于慢性的有明确的肝病史及无明确的肝病史分别为４００例及１２０例。（２）９例急性重型肝炎,出现肝性脑病７例,均在７天内出现,３６例亚急性及５２０例慢性重型肝炎患者,在１２周内达到重型肝炎诊断标准分别为１００．０％及８２．２％。（３）急性重肝炎肆生的肝性脑病均为首先出现,无１例发生腹水,亚急性重型肝炎及慢性重型肝炎首先出现肝性脑病仅为１１．１％及１．７％。仅发生腹水分别为５．６％及３．５％。（４）无明确肝病史的１２０例患者,最后诊断为慢性重型肝炎早、中及晚期分别为在７例、３１例及７２例。结论 （１）重型肝炎依发病基础分为     

影响重型肝炎患者预后的危险因素研究

目的 研究影响重型肝炎患者预后的危险因素。方法收集75例重型肝炎患者（存活组39例，死亡组36例）28项临床指标，采用Cox比例风险模型研究影响重型肝炎患者生存的危险因素与生存状态及生存时间的综合性量化关系。结果白细胞、血小板、总胆红素、碱性磷酸酶、胆固醇、凝血酶原活动度、透明质酸、肝性脑病、肝肾综合征、电解质紊乱、腹水、感染在存活组和死亡组之间差异有统计学意义（P〈0．05）。Cox模型分析显示，凝血酶原活动度、肝性脑病、感染是影响重型肝炎患者预后的主要危险因素（相对危险度分别为0．963、4．107、0．258，P〈0．05）。结论重型肝炎预后影响因素众多，凝血酶原活动度、肝性脑病和感染为主要危险因素，可望用于重型肝炎的预后判断。     

重型肝炎

乳果糖口服与食醋灌肠治疗肝性脑病疗效分析，重症肝炎与非重症肝炎原位肝移植术中机体内环境的对比性研究，自体骨髓干细胞移植治疗慢性重症肝病60例，重型肝炎预后危险因素36例分析，连续静-静脉血液滤过治疗肝性脑病的护理，格林-巴利综合征并重症肝炎患的观察及护理，     

Altered erythrocyte Na+ + K+ pump in adolescent obesity

The number of $\text{Na}\text{K}$ pump units and the cation transport activity of the pump were measured in erythrocytes from two etiologically different groups of obese adolescents and a group of normal controls. There was a significant reduction in the number of pump units, as measured by saturation ouabain binding, in erythrocytes from adolescents with idiopathic, early onset obesity. Individuals whose obesity developed subsequent to the appearance of a variety of hypothalamic lesions showed no reduction in the red cell complement of $\text{Na}\text{K}$ pump when compared to controls and the cation transport activity of their cells was higher than both the controls and the subjects with idiopathic obesity. These results support data obtained in adults that reduced red cell $\text{Na}\text{K}$ pump levels are seen in a group of individuals with idiopathic obesity. They further suggest that such reductions are not likely to be secondary to the obese state per se.     

Transport of Mg2+ by Na+-Mg2+ exchange

Intracellular free Mg(2+) concentration is maintained at low levels by active extrusion from the cells. One of postulated mechanisms is the Na(+)-Mg(2+) exchange, which extrudes Mg(2+) in exchange with Na(+) influx. Although the Na(+)-Mg(2+) exchange activity has been reported in many types of cell, including neurons, details of molecular mechanisms are only poorly understood. In this chapter, we briefly will review our current knowledge on [1] stoichiometry of the Na(+)-Mg(2+) exchange, [2] interaction between the Na(+)-Ca(2+) exchange and the Na(+)-Mg(2+) exchange, [3] molecular biology of the Na(+)-Mg(2+) exchanger.     

Difference between human red blood cell Na+-Li+ countertransport and renal Na+-H+ exchange

Several laboratories have reported that the activities of sodium-lithium countertransport are increased in red blood cells from patients with essential hypertension. Based on the many similarities between this transport system and the renal sodium-proton exchanger, a hypothesis has been put forth in the literature that increased red blood cell sodium-lithium countertransport activity may be a marker for increased sodium-proton exchange activity in the renal proximal tubule. The present studies were designed to test the hypothesis that sodium-lithium countertransport in red blood cells from humans or rabbits is mediated by the same transport mechanism that mediates sodium-proton exchange in the renal brush border from those species. Similar to what has been reported for the rabbit, the present studies show that an amiloride-sensitive sodium-proton exchanger is present in human renal brush border vesicles. However, Na+-Li+ countertransport in human and rabbit red blood cells, assayed under several different conditions, was not inhibited by amiloride. In agreement with what has been reported for humans, the present studies show that extracellular proton-stimulated sodium efflux is inhibited by amiloride in rabbit red blood cells. These data demonstrate a difference (amiloride sensitivity) between the red blood cell sodium-lithium countertransporter and the renal brush border sodium-proton exchanger in humans and rabbits. These experiments detract from the hypothesis that increased red blood cell sodium-lithium countertransport activity in patients with essential hypertension is a marker for increased sodium-proton exchange activity in the renal brush border.     

Red blood cell Li+-Na+ countertransport, Na+-K+ cotransport, and the hemodynamics of hypertension

Red blood cell Li+-Na+ countertransport and Na+-K+ cotransport activities, home blood pressure, invasive systemic hemodynamics, and limb venous compliance were measured in 65 white men (23 normotensive, 22 borderline hypertensive, and 20 mild essential hypertensive subjects). Li+-Na+ countertransport activity was positively and significantly correlated with subject-determined home systolic blood pressure (r = 0.31, p less than 0.02) and with directly measured systolic (r = 0.29, p less than 0.02) and diastolic (r = 0.27, p less than 0.03) blood pressures in the hemodynamic laboratory, independent of potential confounding variables. Analysis of the hemodynamic determinants of blood pressure revealed a significant positive correlation of countertransport with vascular resistance (r = 0.30, p less than 0.02) but not with cardiac output or cardiac index. High red blood cell Na+-K+ cotransport activity was not independently associated with hypertension or with a characteristic hemodynamic pattern but was related to decreased venous compliance. Red blood cell Li+-Na+ countertransport deserves further study as a marker for the genetic substrate of human essential hypertension. Red cell Na+-K+ cotransport may be altered secondarily by factors related to high blood pressure and seems to be a valid marker for abnormalities of the venous system in hypertension.     

Ca2+-dependent structural rearrangements within Na+-Ca2+ exchanger dimers

Cytoplasmic Ca(2+) is known to regulate Na(+)-Ca(2+) exchanger (NCX) activity by binding to two adjacent Ca(2+)-binding domains (CBD1 and CBD2) located in the large intracellular loop between transmembrane segments 5 and 6. We investigated Ca(2+)-dependent movements as changes in FRET between exchanger proteins tagged with CFP or YFP at position 266 within the large cytoplasmic loop. Data indicate that the exchanger assembles as a dimer in the plasma membrane. Addition of Ca(2+) decreases the distance between the cytoplasmic loops of NCX pairs. The Ca(2+)-dependent movements detected between paired NCXs were abolished by mutating the Ca(2+) coordination sites in CBD1 (D421A, E451A, and D500V), whereas disruption of the primary Ca(2+) coordination site in CBD2 (E516L) had no effect. Thus, the Ca(2+)-induced conformational changes of NCX dimers arise from the movement of CBD1. FRET studies of CBD1, CBD2, and CBD1-CBD2 peptides displayed Ca(2+)-dependent movements with different apparent affinities. CBD1-CBD2 showed a Ca(2+)-dependent phenotype mirroring full-length NCX but distinct from both CBD1 and CBD2.     

Na+-Li+ countertransport in essential hypertension

Several studies on Na+-Li+ countertransport have reported higher rates in essential hypertensive than in normotensives, with a distribution pattern which is dependent on racial and ethnic background. However, it is not well established whether this abnormality in Na+ transport is associated with an abnormal clinical setting. In the present study we have performed a kinetic analysis of the interaction of the Na+-Li+ countertransport system with internal Na+ in erythrocytes from a sample of 72 essential hypertensives and 30 normotensive controls. A significant increase in mean values of the maximal rate of Li+-stimulated Na+ efflux (Vmax; 375.1 +/- 23.8 versus 213.7 +/- 8.5 mumol/l cells per h; mean +/- s.e.m.; Mann-Whitney test: U = 500; P less than 0.0001), as well as in the apparent affinity constant for internal Na+ (KNa; 10.03 +/- 0.08 versus 6 +/- 0.4 mmol/l cells; Mann-Whitney test: U = 718; P less than 0.0079), were observed in essential hypertensives with respect to normotensives. Using the 95% confidence interval of Vmax in normotensives as the normal range, 29 (40.3%) of the essential hypertensives exhibited values above the normal upper limit. The maximal rate (Vmax) and the internal Na+ content required for half-maximal stimulation (K50%) of Na+-K+ ATPase and outward Na+-K+ cotransport, and the rate constant of Na+ leak (KPNa) in this subset were similar to the values observed in the controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

Rapamycin selectively expands CD4+CD25+FoxP3+ regulatory T cells

Rapamycin is an immunosuppressive compound that is currently used to prevent acute graft rejection in humans. In addition, rapamycin has been shown to allow operational tolerance in murine models. However, a direct effect of rapamycin on T regulatory (Tr) cells, which play a key role in induction and maintenance of peripheral tolerance, has not been demonstrated so far. Here, we provide new evidence that rapamycin selectively expands the murine naturally occurring CD4(+)CD25(+)FoxP3(+) Tr cells in vitro. These expanded Tr cells suppress proliferation of syngeneic T cells in vitro and prevent allograft rejection in vivo. Interestingly, rapamycin does not block activation-induced cell death and proliferation of CD4(+) T cells in vitro. Based on this new mode of action, rapamycin can be used to expand CD4(+)CD25(+)FoxP3(+) Tr cells for ex vivo cellular therapy in T-cell-mediated diseases.     

Red cells from the original JAL+ proband are also DAK+ and STEM+

Background The low‐prevalence Rh antigen, JAL, was named after the index case, Mr. J. Allen. Based on reactivity of seven multi‐specific sera with his RBCs, it was apparent that they express at least one additional low‐prevalence antigen. The purpose of this study was to investigate the other low‐prevalence antigen(s) on J. Allen’s RBCs. Methods Blood samples and reagents were from our collections. Hemagglutination and DNA analyses were performed by standard methods. Results Our DNA analyses confirmed the presence of RHCE*ceS(340T) in J. Allen and revealed the presence of RHCE*ceBI (ce 48C, 712G, 818T, 1132G) and RHD*DOL (509T, 667T). RBCs from J. Allen were agglutinated by anti‐JAL, anti‐STEM, and anti‐DAK. Two of the reactive multi‐specific sera reported in the original paper reacted with RBCs from J. Allen, and with RBCs from four other people with RHCE*ceBI, including the original STEM+ index case (P. Stemper) but not with RBCs with the DIIIa, DAK+ phenotype. We conclude that they contain anti‐STEM. Conclusion J.Allen’s RBCs express the low‐prevalence Rh antigens, JAL, V/VS (extremely weakly), STEM, and DAK. The presence of JAL on the variant Rhce, RhceJAL (16Cys, 114Trp, 245Val), STEM on the variant Rhce, RhceBI (16Cys, 238Val, 273Val, 378Val), and DAK on the variant RhD (170Thr, 223Val), encoded by RHD*DOL in trans to RHCE*ceBI is consistent with expression of these antigens. When J. Allen RBCs are used to detect and identify an anti‐JAL, it is important to remember that they also express STEM and DAK.