Oxidant Stress in Hemodialysis Patients: What Are the Determining Factors?

Oxidant stress contributes to morbidity in hemodialysis patients. Three possible causes of oxidant stress have been suggested: the uremic state, the dialyzer membrane, and bacterial contaminants from the dialysate. Oxidant stress occurs in uremia before dialysis therapy is initiated, as evidenced by increased production of reactive oxygen species, increased levels of oxidized plasma proteins and lipids, and decreased antioxidant defenses. It has been proposed that increased production of reactive oxygen species during hemodialysis is also an important contributor to oxidant stress. Hemodialysis is associated with a transient increase in production of reactive oxygen species, particularly with cellulose membranes. In addition, surveys have shown widespread contamination of dialysate by endotoxin, which may cross membranes and prime production of reactive oxygen species by phagocytic cells. Recent studies, however, show a decrease in protein oxidation from pre- to post-dialysis and a normalization of neutrophil reactive oxygen species production. Taken together, these data suggest that uremia, per se, is the most important cause of oxidant stress in hemodialysis patients. Dialysate quality may also contribute to oxidant stress, but evidence that the dialyzer membrane plays a role is weak.     

Neonatal endotoxin exposure modifies the acoustic startle response and circulating levels of corticosterone in the adult rat but only following acute stress

A variety of early life stressors have consistently been implicated in the development of psychopathology in adulthood. The current study investigates a rarely considered form of early life stress, bacterial infection, for its ability to induce psychopathology-like symptoms in adult rat. Specifically, neonatal rats were exposed to a simulated bacterial infection. In adulthood the acoustic startle response of these animals was evaluated both prior to and following exposure to restraint stress. Our results indicate that animals neonatally exposed to infection exhibit a significantly exaggerated acoustic startle response but only following exposure to stress. Additionally, we observed that adult animals neonatally exposed to infection, exhibited increased production of circulating corticosterone following stress, indicating potentiated hypothalamic pituitary adrenal axis activity as well as altered novelty seeking behaviour and locomotor activity. These results extend upon existing pre-clinical findings that indicate certain stressful early life events can predispose the adult animal to exhibit abnormal behaviour in adulthood.     

幼年感染细菌内毒素与成年后多种疾病易感性的关系

生命早期的环境因素与成年后许多病理学易感性的改变有关。研究显示,幼年时期感染细菌内毒素与成年后炎症性、自身免疫性、代谢性、神经精神性疾病及肿瘤的发生密切相关。本文系统综述了幼年时期受细菌内毒素损害对成年后多种疾病的发生所起的远隔后效应,讨论了幼年感染细菌内毒素是否通过影响神经内分泌系统和免疫系统的发育从而改变成年个体神经内分泌系统和免疫系统的功能以及对多种疾病的易感性,揭示了幼年时期的感染和炎症因素是规划个体神经内分泌系统和免疫系统发育的重要刺激因子。     

丙泊酚对内毒素性急性肺损伤大鼠肺组织c-Jun氨基末端激酶活性的影响

目的 探讨大鼠内毒素性急性肺损伤(acute lung injury,ALI)时应用丙泊酚后处理对肺组织磷酸化c-Jun氨基末端激酶(phospho-c-Jun terninal kinnase,p-JNK)的影响.方法 96只雄性SD大鼠按数字随机表法分为4组(每组24只):生理盐水对照组(A组);内毒素[有效成分为...     

血清降钙素原检测对于肾移植术后肺部感染的诊断价值

目的：与内毒素和C反应蛋白（ CRP）检测结果进行比较,探讨血清降钙素原（ PCT）检测在肾移植术后肺部感染诊断中的临床意义及其应用价值。方法回顾性分析2010年2月至2013年9月武汉大学移植医学中心98例肾移植术后并发肺部感染的受者临床资料。根据肺部感染的病原体诊断标准将受者分为细菌组（48例）和非细菌组（50例）,比较PCT、内毒素和CRP检测3种方法诊断肾移植术后细菌性肺部感染的灵敏度和特异度,比较3种方法对确诊肾移植术后并发细菌性肺部感染受者的阳性诊断结果。结果 PCT 检测灵敏度为95.8％,特异度为94．0％;内毒素检测灵敏度为77．1％,特异度为72．0％;CRP检测灵敏度为52．1％,特异度为58．0％。血清PCT检测细菌组受者阳性结果高于内毒素和CRP检测（χ2＝7.36,10．04, P均＜0．05）。结论血清PCT检测对于肾移植术后细菌性肺部感染的临床诊断价值高于内毒素和CRP,可作为肾移植受者是否并发细菌性肺部感染的优选诊断指标。     

盐酸左氧氟沙星注射液细菌内毒素检查法的研究

目的：探讨建立盐酸左氧氟沙星沙星注射液细菌内毒素检查法,方法：用不同厂家的鲎试剂对3批样品进行干扰试验,结果：盐酸左氧氟沙星注射液在6倍稀释时无干扰作用,结论：可以用鲎试验法代替家兔法检查盐酸左氧氟沙星注射液中的热原。     

高迁移率族蛋白1参与脓毒症大鼠急性呼吸窘迫综合征时中性粒细胞的凋亡

目的 探究脓毒症大鼠急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS)时高迁移率族蛋白1(high mobility group box 1,HMGB1)参与中性粒细胞(polymorphonuclear neutrophils,PMN)凋亡延迟的相关机制及正丁酸钠(sodium butyrate,SB)的干预效果. 方法 采用随机数字表法将90只健康成年雄性Sprague-Dawley(SD)大鼠随机分为正常对照组(NS组,6只)、内毒素(lipopolysaccharide,LPS)致伤组(LPS组,42只)、HMGB1抑制剂SB干预组(SB组,42只),LPS组、SB组又分为7个时相点(LPS致伤后0.5、1、2、6、12、24、48 h),每个时相点6只动物.LPS组,腹腔注射LPS 5 mg/kg;SB组,腹腔注射LPS 5 mg/kg后0.5 h静脉注射SB,每次剂量500 mg/kg;NS组,腹腔注射生理盐水1 ml.LPS组、SB组于LPS注射后各时点,颈静脉取血检查PMN,取血后左肺灌洗收集支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF),取右肺中叶行HMGB1 mRNA检测;于LPS注射12h时点(NS组大鼠留取颈静脉血、收集BALF、取右肺中叶行HMGB1 mRNA检测),3组大鼠收集左肺BALF后,取右肺下叶检测肺组织湿/干重比(wet/dry weight ratio,W/D),取右肺上叶进行病理组织学检查;于24、48 h时点,LPS组、SB组取右肺下叶检测肺组织W/D、取右肺上叶进行病理组织学检查. 结果 与NS组比较,LPS组肺组织中HMGB1 mRNA表达量明显增高,24 h达最大值,差异有统计学意义(P＜0.05);SB组的HMGB1 mRNA表达量减少,差异有统计学意义(P＜0.05).LPS组BALF中凋亡早期PMN表达量与NS组类似,但凋亡晚期PMN变化则不同,LPS组外周血中凋亡晚期PMN细胞高于NS组(P＜0.05),LPS组BALF中凋亡晚期PMN细胞均低于NS组(P＜0.05).LPS 12 h组BALF的PMN百分比明显高于NS组[(49.1±6.8)、(2.7±0.5)],差异有统计学意义(P＜0.01).LPS组肺组织光镜下可见肺泡腔水肿,支气管壁中发现PMN浸润,肺泡壁毛细血管扩充血.LPS24 h组肺组织的W/D明显高于NS组[(6.71±0.12)、(4.18±0.26)],差异有统计学意义(P＜0.05).SB干预组的HMGB1 mRNA表达量减少,早期凋亡率类似,SB组的BALF晚期凋亡率高于同时点LPS组的BALF,SB外周血组晚期凋亡低于同时点LPS外周血组,差异有统计学意义(P＜0.05).SB组BALF的PMN百分比、肺组织病理损伤程度、W/D均低于LPS组,差异有统计学意义(P＜0.05). 结论 在大鼠ARDS中,HMGB1 mRNA表达较晚,但持续时间长,SB对HMGB1有潜在的治疗作用,HMGB1可能参与PMN凋亡机制的调节.     

NF-κB诱骗寡核苷酸对内毒素性肝损伤的保护作用和机制

目的探讨NF-κB诱骗寡脱氧核苷酸对大鼠内毒素性肝损伤的保护作用及其机制。方法60只SD大鼠随机分为对照组、内毒素(LPS)组、诱骗寡核苷酸(decoy ODNs)处理组。取各组大鼠肝组织检测NF-κB蛋白结合活性(EMSA),观察组织病理学改变(光镜)及肝细胞凋亡(TUNEL)。取静脉血检测AST(自动生化仪)以及TNF-α,IL-6的表达水平(ELISA)。结果与对照组相比,内毒素组NF-κB活性明显升高,诱发大量肝细胞凋亡,肝脏损伤明显;同时血清AST,TNF-α及IL-6明显升高(P0.01)。与内毒素组相比,NF-κB诱骗寡核苷酸处理组NF-κB活性受抑制(P0.01)、肝脏组织病理学改变和肝细胞凋亡明显减轻,血清中TNF-α和AST表达水平降低(P0.01),但IL-6表达与内毒素组差异无统计学意义(P0.05)。结论NF-κB诱骗策略能高效抑制NF-κB的活性,抑制其下游有害细胞因子的产生,从而减轻内毒素性肝损伤。     

手术/创伤后外周静脉血内毒素的研究

目的探讨健康成人和创伤病人外周静脉血内毒素水平及其与创伤的关系。方法采用偶氮显色鲎试验检测５０例健康成人及５１例不同手术／创伤病人外周静脉血的内毒素。结果（１）此法检测内毒素可达微量（１０－２Ｅｕ／ｍｌ,ｎ＝５）,重复性较好（ＣＶ＝２．２９％,ｎ＝５）。（２）本法测得健康成人外周静脉血内毒素＜０．０３３Ｅｕ／ｍｌ,与国际水准一致。（３）病人术后３天内毒素升高（Ｐ＜０．０１）。（４）病人外周静脉血内毒素与创伤程度呈正相关,Ｒ２＝０．６６７。结论本法测定血微量内毒素是可行的。外周静脉内毒素水平随创伤程度增加而增加。     

Management of abdominal sepsis

Introduction: Today the management of the different forms of peritonitis is generally standardised. The classification of primary and secondary peritonitis is well accepted. From a pathophysiological point of view, postoperative and post-traumatic peritonitis should be considered as independent entities. The bacteriological isolates from the inflamed peritoneal cavity do not correlate with the clinical course, and the occurrence of enterococci and bacteroides may be slightly related to ongoing infectious complications. Classification: Valuable scoring systems mainly rely on systemic signs of the septic disease and seem to better differentiate the prognosis of the disease than more surgically oriented scores do. Although the scoring systems did not allow any clinical decision, they should be used to help better compare patients treated in different institutions. The observation of the minor relevance of bacteriology and the superiority of general sepsis scores agrees with the fact that pre-existing septic organ dysfunction and pre-existing comorbidity are the main determinants of mortality. Treatment: Surgical therapy focuses on the control of the source of infection because it has been clearly shown that, without resolving the source of infection, the prognosis remains poor. Adjuvant surgical measures aim at the further reduction of the bacterial load in the peritoneal cavity. Planned relaparotomy, relaparotomy on demand, and continuous closed peritoneal lavage are used. Results: Clinical results proved these methods to be equally effective although pathophysiological considerations favour closed peritoneal lavage. Conclusion: Summarising the available data, we need a more sophisticated understanding of the pathophysiology of the peritonitis, and well-designed clinical studies are necessary to define the optimal surgical treatment modalities. Received: 27 November 1997