革兰氏阴性菌败血症治疗期间内毒素血症和菌血症的动态变化

尽管接受了具有高度体外抗菌活性的抗生素,许多革兰氏阴性菌败血症病人的临床状况仍在继续恶化。动物实验发现,在有效抗菌治疗后不久,感染动物的内毒素血症明显加剧。然而对于败血症病人,却从未进行添毒素血症的动态监测。     

血内毒素快速定量测定的临床应用体会

在临床工作中,革兰阴性菌感染引起的败血症是住院患者死亡的重要原因之一[1].它主要通过内毒素(革兰阴性菌细胞壁最外层的一种脂多糖成分)致病,通常当患者发生严重细菌感染、严重休克、脓毒血症、系统性炎症反应综合征(SIRS)、多器官功能衰竭等时,血内毒素水平升高.     

血清内毒素定量检测在慢性乙型肝炎患者中的应用

目的探讨血清内毒素定量检测在慢性乙型肝炎住院患者中的应用价值。方法 采用BET-24A细菌内毒素分析仪对中南大学湘雅医院60例慢性乙型肝炎住院患者及15例健康体检者血清标本进行内毒素定量测定,并结合是否有合并自发性腹膜炎等临床资料,进行综合分析。结果慢性乙型肝炎患者血清内毒素检测值高于健康体检者,差异有统计学意义（P〈0.05）;其中合并有自发性腹膜炎的慢性乙型肝炎患者血清内毒素检测值高于其他慢性乙型肝炎患者,差异有统计学意义（P〈0.05）。结论慢性乙型肝炎患者常常合并有内毒素血症,其中合并有自发性腹膜炎患者内毒素血症更明显,预后更差。BET-24A细菌内毒素分析仪能够简单、快速、准确检测出结果,具有临床实用价值,值得推广。     

内毒素和抗生素杀菌滤液刺激全血细胞产生肿瘤坏死因子的作用

目的对革兰氏阴性菌（ＧＮＢ）内毒素（ＬＰＳ）和抗生素杀菌滤液刺激全血细胞产生肿瘤坏死因子（ＴＮＦα）的作用进行研究。方法以单次大量和重复小剂量ＬＰＳ及头孢他啶和亚胺配能杀菌滤液,分别刺激体外培养的全血细胞,以ＥＬＩＳＡ法测定培养上清液的ＴＮＦα水平。结果全血细胞培养２４小时后,单个核细胞存活率仍在９５％以上,没有加入ＬＰＳ的全血细胞均无ＴＮＦα产生,ＬＰＳ刺激全血细胞产生ＴＮＦα呈剂量依赖关系。重复小剂量ＬＰＳ刺激较单次大量给予,可刺激全血细胞产生更高水平的ＴＮＦα。头孢他啶组的杀菌滤液能引起更多ＴＮＦα释放,与亚胺配能组及无抗生素组比较有显著差异。多粘菌素Ｂ可抑制各组刺激全血细胞产生ＴＮＦα的能力。结论全血细胞培养可以作为研究ＬＰＳ和ＴＮＦα关系的体外模型,临床ＧＮＢ败血症患者中,少量内毒素的持续存在可能对患者的危害更大。在治疗ＧＮＢ感染时,应当考虑抗生素杀灭细菌,使细菌释放ＬＰＳ的能力,而且中和内毒素毒性作用的药物可能是有效的辅助治疗手段。     

血必净注射液细菌内毒素检查法的研究

目的:建立血必净注射液的细菌内毒素检查法.方法:将血必净注射液经12倍稀释,用标示灵敏度为0.25EU·ml-1的鲎试剂检测其细菌内毒素.结果:血必净注射液稀释12倍对鲎试剂无干扰作用.结论:可以用细菌内毒素检查法对血必净注射液进行热原检查.     

脓毒症相关概念的变化及其意义

既往对外科患者是否选用抗生素或选用何种抗生素治疗 ,往往根据患者是否存在感染病灶 ,是否有菌血症、败血症、脓毒血症等现象来判断 ;主要强调细菌、毒素、细菌培养结果及药敏试验对选择抗生素的作用 ;认为感染和机体全身反应同一病理概念 ,即感染到一定程度势必产生全身性反应 ,细菌等病原微生物入侵与机体的各种反应均发生了直接联系。因此 ,长期以来 ,感染、菌血症、败血症、脓毒症、脓毒性休克等名词互换使用 ,但又不能反映疾病的本质、病理过程及预后 ,给感染及脓毒症的基础和临床研究带来了一定困难。另一方面 ,脓毒症、脓毒性休克极…     

危重病患者抗生素相关性肠炎临床特征观察

目的观察危重病患者合并抗生素相关性肠炎的临床特征及治疗效果,以降低疾病发生率。方法收集2011年12月-2013年1月45例危重病患者合并抗生素相关性肠炎患者的临床资料,对其临床表现、实验室检查及危险因素及治疗情况等进行回顾性分析。结果危重病患者合并抗生素相关性肠炎临床表现中以腹泻最为明显,发生率为100.0%,腹泻与其他临床表现比较差异有统计学意义(P<0.05);实验室检查中潜血阳性明显,血培养均显示阴性,大便培养以难辨梭状芽胞杆菌居多;APACHEⅡ评分和白蛋白值是危重病患者合并抗生素相关性肠炎发生的危险因素;经抗菌药物及口服双歧杆菌等肠道活菌制剂治疗后预后理想。结论腹泻是危重病患者合并抗生素相关性肠炎的主要临床表现,实验室检查以白细胞增高、大便培养有细菌等为主。     

肾移植患者围手术期营养状况和营养治疗效果评价

目的评价肾移植患者围手术期营养状况和营养治疗效果。方法对48例肾移植患者围手术期的营养状况和营养治疗效果进行了评价。接受同种异体肾移植患者48例,平均年龄(43.4±9.1)岁,其中男43例,女5例。术前均为接受透析治疗的尿毒症期慢性肾病患者,病史5～14年。入院时体重评价营养不足为66.7%,54.2%患者三头肌皮褶厚度低于正常值50%,体质脂数与体重营养评价结果相似;血清三酰甘油酯均显著增高,男性为(3.4±0.5)mmol/L,女性为(3.9±0.7)mmol/L,血清脂蛋白apo-a含量高于正常值。所有患者血清蛋白低于90g/L,75.0%患者血清总蛋白、白蛋白、淋巴细胞明显低于正常值,视黄醇结合蛋白偏高。血清必需氨基酸含量均较低,同型半胱氨酸含量明显升高。血磷含量高于正常值。结果肾移植手术成功后,第14d时营养状况明显改善,体重平均增加2.24kg,血清三酰甘油酯明显降低,与术前相比有显著性差异。79.2%的患者血红蛋白恢复到正常值范围。血清总蛋白、白蛋白、淋巴细胞明显增高,视黄醇结合蛋白有所下降。血清必需氨基酸含量回升,同型半胱氨酸浓度与正常值接近,血磷恢复正常。结论肾移植患者术前营养不足较为严重,并有高脂血症、贫血、低蛋白血症和高磷血症,肾移植手术成功后经适当营养治疗后患者的营养状况有明显改善术。     

急性白血病感染败血症的危险因素分析及耐药性研究

[目的]探讨影响急性白血病(AL)感染败血症的危险因素,并对产生的病原菌进行药敏研究,为治疗继发败血症提供临床依据. [方法]对温州市中心医院2004年12月-2010年1月73例继发败血症的急性白血病患者临床资料进行回顾研究,将9种可能引起败血症的危险因素进行统计分析,再建立logistic回归模型;将病原菌分离后进行药敏实验,观察细菌分布及耐药情况.[结果]从9种可能的危险因素中筛选出5种主要的危险因素,分别为使用抗生素、年龄、住院时间、手术时间及白细胞计数;利用纸片扩散法(K-B法)检测细菌耐药情况,发现该院白血病继发败血症的细菌耐药情况十分严重. [结论]使用抗生素、年龄、住院时间、手术时间和白细胞计数是急性白血病继发败血症的独立危险因素,需要加强管理,尤其是对抗生素要加强使用规范,倡导合理用药.     

乙型脑炎减毒活疫苗细菌内毒素凝胶法的检测

目的建立乙型脑炎减毒活疫苗细菌内毒素检测方法和质量标准,检测样品中的内毒素含量。方法中国药典2010年版三部细菌内毒素检测法(凝胶限度试验、凝胶半定量试验)。结果选用λ为0.5 EU/ml的鲎试剂,采用凝胶限度法对乙型脑炎减毒活疫苗进行细菌内毒素检查,样品经稀释至80倍或以上稀释度后对内毒素检查均无干扰,确定该疫苗的内毒素限度值为40 EU/ml[即20 EU/剂(0.5 ml)]。凝胶限度试验结果显示,疫苗每1 ml中含内毒素的量均小于40EU,即每1次人用剂量(0.5 ml)中含内毒素的量均小于20 EU。凝胶半定量测定结果显示,1人份规格疫苗中含内毒素的量为2.50～10.00 EU/ml(平均5.36 EU/ml);5人份规格疫苗中含内毒素的量为1.50～6.00 EU/ml(平均3.02 EU/ml)。结论凝胶法两种试验均可用于乙型脑炎减毒活疫苗细菌内毒素检测,与凝胶半定量试验相比,凝胶限度试验更为简便、且易于操作;采用凝胶限度法本研究建立了乙型脑炎减毒活疫苗细菌内毒素检测方法和质量标准;凝胶半定量法测定结果用准确数据显示该疫苗的内毒素含量均在人体安全限度以内。     

Of microbes and meals: the health consequences of dietary endotoxemia

The human intestinal tract comprises a rich and complex microbial ecosystem. This intestinal microbota provides a large reservoir of potentially toxic molecules, including bacterial endotoxin (ie, lipopolysaccharide [LPS]). This potent inflammatory molecule is detectable in the circulation of healthy individuals, and levels transiently increase following ingestion of energy-rich meals. Chronic exposure to circulating endotoxin has been associated with obesity, diabetes, and cardiovascular disease. Western-style meals augment LPS translocation and by this mechanism may contribute to the pathogenesis of these diseases. By contrast, the gut and other organs have evolved mechanisms to detoxify endotoxin and neutralize the potentially inflammatory qualities of circulating endotoxin. Of specific interest to clinicians is evidence that acute postprandial elevation of circulating endotoxin is dependent on meal composition. In this review, the authors present an overview of the biochemical and cellular mechanisms that lead to endotoxemia, with emphasis on the interplay between microbial and nutrition determinants of this condition. The link between endotoxemia, diet, and changes in the intestinal microbiota raise the possibility that dietary interventions can, at least in part, ameliorate the detrimental outcomes of endotoxemia.     

Chronic administration of dietary grape seed extract increases colonic expression of gut tight junction protein occludin and reduces fecal calprotectin: a secondary analysis of healthy Wistar Furth rats

Animal studies have demonstrated the potential of grape seed extract (GSE) to prevent metabolic syndrome, obesity, and type 2 diabetes. Recently, metabolic endotoxemia induced by bacterial endotoxins produced in the colon has emerged as a possible factor in the etiology of metabolic syndrome. Improving colonic barrier function may control endotoxemia by reducing endotoxin uptake. However, the impact of GSE on colonic barrier integrity and endotoxin uptake has not been evaluated. We performed a secondary analysis of samples collected from a chronic GSE feeding study with pharmacokinetic end points to examine potential modulation of biomarkers of colonic integrity and endotoxin uptake. We hypothesized that a secondary analysis would indicate that chronic GSE administration increases colonic expression of intestinal tight junction proteins and reduces circulating endotoxin levels, even in the absence of an obesity-promoting stimulus. Wistar Furth rats were administered drinking water containing 0.1% GSE for 21 days. Grape seed extract significantly increased the expression of gut junction protein occludin in the proximal colon and reduced fecal levels of the neutrophil protein calprotectin, compared with control. Grape seed extract did not significantly reduce serum or fecal endotoxin levels compared with control, although the variability in serum levels was widely increased by GSE. These data suggest that the improvement of gut barrier integrity and potential modulation of endotoxemia warrant investigation as a possible mechanism by which GSE prevents metabolic syndrome and associated diseases. Further investigation of this mechanism in high-fat feeding metabolic syndrome and obesity models is therefore justified.     

酒精性肝病患者血浆内毒素水平检测及临床意义

目的　检测不同阶段酒精性肝病患者的外周血内毒素水平 ,探讨此类肝病患者内毒素血症的发病情况 ,以指导治疗。方法　选择酒精性脂肪肝、酒精性肝炎、酒精性肝硬化患者与正常对照组 ,4组共 98例。测外周血浆内毒素定量。结果　酒精性脂肪肝、酒精性肝炎、酒精性肝硬化内毒素血症的发病率分别为 1 2 1 2 %、55 55 %及68 0 1 % ,高于正常对照组 (9 0 0 % ) ,酒精性肝炎、酒精性肝硬化与正常对照组比较差异显著 (P <0 .0 1 )。酒精性脂肪肝、酒精性肝炎、酒精性肝硬化血浆内毒素含量较正常对照组相比升高 ,后二者同正常对照组比较差异显著 (P <0 .0 1 )。结论　酒精性肝病患者内毒素血症发病率增高 ,纠正内毒素血症治疗 ,对酒精性肝病恢复有重要作用     

外科手术患者血中细菌DNA的检出率

休克、创伤、长时间肠外营养可能导致肠道细菌移位,应用聚合酶链反应(PCR)技术检测外科病人血中的肠源性细菌DNA国内尚无报道。     

偶氮显色鲎试验定量测定人体外周静脉血微量内毒素的研究

目的建立偶氮显色鲎试验并测定健康人和临床病人外周静脉血内毒素。     

Nutritional effects of salmonellosis in mice.

Mice infected with a standard challenge of Salmonella typhimurium manifest a number of changes associated with endotoxemia. These changes result in profound alterations in the nutritional and metabolic status of the host. Food and water intake approaches levels of total inanition, blood glucose declines more rapidly than in fasted controls, hepatic phosphoenolpyruvate carboxykinase (the enzyme that is rate limiting in gluconeogenesis) shows diminished activity and loss of cortisol inducibility, and hypothermia, rather than hyperthermia, becomes acute. These changes occur at a time when bacteremia is first demonstrable. This occurs on the 3rd day after infection under the conditions employed. Death occurs in most mice within the next 24 to 48 hr. Mice vaccinated with a highly immunogenic ribosomal preparation and subsequently infected with the standard number of organisms did not manifest the above changes. Other work from this laboratory has established that effects of the type described are elicited by bacterial endotoxin as a result of mediating substances released into the blood by cells of the reticuloendothelial system. Presumably these substances appear in blood of infected mice as well.     

慢性乙型肝炎患者肠源性内毒素血症中免疫调节细胞因子表达变化的研究

目的：研究慢性乙型肝炎（chronic hepatitis B,CHB）患者肠源性内毒素血症（intestinal endotoxemia, IETM）中与调节性T细胞（regulatory T cells,Treg）、Th17细胞相关免疫调节细胞因子的表达变化。方法：应用ELISA法分别对80例CHB患者和20例健康对照者的血浆IL-10、TGF-β、IL-6、IL-17、IL-23及内毒素水平进行检测。根据测定的内毒素水平,将CHB患者分为内毒素阳性组和内毒素阴性组。结果：CHB患者血浆IL-10、TGF-β、IL-6、IL-17、IL-23水平均明显高于健康对照组（Z值分别为5.265、6.859、6.894、5.028、6.877,均P〈0.01）。内毒素阳性组患者明显高于内毒素阴性组和健康对照组（H值分别为45.833、48.423、48.984、75.184、75.814,均P〈0.01）。结论：CHB患者IETM时血浆中与Treg、Th17细胞相关细胞因子水平进一步增高。     

禁食后肠源性内毒素移位途径的动物实验观察

目的：探讨禁食后肠源性内毒素移位的途径。方法：建立禁食大鼠动物模型,以脂多糖灌胃,在不同时间点,观测门静脉,胸导管淋巴液,腹主动脉血的内毒素水平变化,结果：腹主动脉血与胸导管淋巴液中的内毒素浓度变化规律基本一致（P＜0．01）,门静脉注入大量内毒素后,股动脉内毒素水平无明显变化（P＞0．05）。结论：经门静脉进入肝脏的内毒素基本可被肝脏减毒,在禁食状态下,淋巴移位途径在肠源性内毒素移位中起重要作用。     

地衣芽胞杆菌活菌制剂治疗肝病患者肠源性内毒素血症的临床疗效

目的探讨地衣芽胞杆菌活菌制剂对肝病患者肠源性内毒素血症的临床治疗作用。方法将45例肝病且具有肠源性内毒素血症的患者分为观察组和对照组,2组间在性别、年龄、病程、临床特点及血清内毒素水平方面差异无统计学意义,观察组在对照组的基础上加用地衣芽胞杆菌活菌制剂治疗,治疗3周后再次检测2组的血清内毒素水平,并进行统计学分析。结果治疗前2组血清内毒素水平分别为（67.15±29.22）和（65.61±28.17）pg/ml。差异无统计学意义（P〉0.05）。治疗后2组血清内毒素水平分别为（30.84±15.56）和（56.79±27.01）pg/ml（P〈0.05）,差异有统计学意义。结论地衣芽胞杆菌活菌制剂对肝病患者肠源性内毒素血症有治疗作用。     

Effects of total parenteral nutrition on the development of intestinal endotoxemia in rats: a comparison between glucose and lipid

The effects of parenteral nutrition (PN) and of the difference in the PN regimens between glucose and lipid emulsion on the development of endogenous endotoxemia were studied in 40 Wister rats. Endotoxemia was induced by occluding the superior mesenteric vein (SMV) for 30 min. The plasma endotoxin in the portal blood at the time of the release of the SMV occlusion and that in the arterial blood 10 min after the release were quantified. Twenty of the 40 rats had received PN for 48 hr prior to the SMV occlusion. Ten of these 20 rats received the total nonprotein calorie (TNPC) solely with glucose, and the other 10 rats received 25% of the TNPC with lipid emulsion. Ten rats had been allowed free access to lab food until the SMV occlusion. The remaining 10 rats underwent neither the SMV occlusion nor PN, and served as the control group. Both the portal and the arterial endotoxin increased after the release of the SMV occlusion, however the portal endotoxin was higher than that of the arterial one. Both the portal and the arterial endotoxin of the rats supported by PN were significantly lower than those of the rats nourished by lab food, while they were higher than the control values. The difference in the PN regimens did not cause any alteration in the endotoxin levels. These results indicate that the development of intestinal endotoxemia was not influenced by the difference in the PN regimens, but it was rather influenced by a presence of intestinal content.