Adsorption of microorganism components by lixelle beads

We reported previously that Lixelle, which was used for beta-2 microglobulin (BMG) adsorption columns, could adsorb not only BMG but also inflammatory cytokines. We then were interested in the application of Lixelle to patients with systemic inflammatory response syndrome (SIRS) and tried to find out its ability to adsorb microorganism components in vitro using lipopolysaccharide (LPS) (E. coli: B8), endotoxin (ET) containing water, and peptidoglycan (PG: Micrococcus luteus). The initial concentrations of each solution were LPS (ET: 29,135 EU/L), contaminated water (ET: 3,523 EU/L), and PG (67.1 ng/ml) and 2.5 ml of each of the stock solutions and adjusted diluted solutions contained 0.5 ml of Lixelle beads. After shaking at 37 degrees C for 2 h, ET in the solutions was determined by the ET specific-limulus amebocyte lysate (ES-LAL) method and PG by the silkworm larbae plasma (SLP) method. The results revealed that even when ET concentrations in LPS and contaminated water were high, the samples containing Lixelle beads showed significant decreases. There was some adsorption of PG but no significant differences. Thus, Lixelle beads can adsorb not only BMG but also microorganism components such as ET and PG. These findings, together with the ability to adsorb inflammatory cytokines by Lixelle, show the possibility of application for the treatment of infectious SIRS.     

Examining the effects of lipopolysaccharide and cholecystokinin on water ingestion: comparing intake and palatability

Lipopolysaccharide (LPS) and cholecystokinin (CCK) have been shown to have anorectic properties in a variety of species. The present study examined the effects of LPS and CCK, both alone and in combination, on two different aspects of water ingestion, water intake and palatability. On test days, animals were first injected intraperitoneally (i.p.) with either LPS (200 microg/kg) or NaCl vehicle, and 2 h later received a second injection of either CCK (8 microg/kg) or NaCl vehicle. In Experiment 1, water intake was monitored for 1 h on 3 separate test days 72 h apart; while in Experiment 2, water palatability was assessed using the taste reactivity test (TRT), on two separate test days 72 h apart. Both LPS and CCK significantly (p<0.05) reduced water intake, with the effects of combined LPS with CCK being more pronounced than either agent injected alone. Rats developed a rapid tolerance to the effects of LPS on water intake on subsequent exposures to LPS. Results from the TRT indicated that LPS enhanced water palatability (p<0.05), as evidenced by a high level of ingestive responding, whereas CCK produced a pattern of responding indicative of satiety. LPS plus CCK reduced ingestive responding on the first test day, but these responses were significantly increased on the second test day (p<0.05). These results demonstrate that although LPS reduces water intake, it enhances water palatability. The results further underscore the necessity for examining palatability changes in addition to intake measures when studying the regulation of feeding and drinking.     

超滤技术制备阿昔洛韦葡萄糖注射液及质量检查

目的研究超滤技术制备阿昔洛韦葡萄糖注射液及其内毒素检查的方法。方法采用超滤技术制备阿昔洛韦葡萄糖注射液,并依据2000年版中国药典及其相关标准检查大输液质量。结果输液质量符合2000年版中国药典及相关标准的有关规定。结论超滤技术制备阿昔洛韦葡萄糖注射液工艺流程短,操作简单,可采用内毒素检查法检查其内毒素含量。     

大黄对肠源性感染早期肺损伤大鼠内毒素的影响

目的：观察大黄治疗大鼠肠源性肺损伤时内毒素变化。方法：采用大鼠盲肠结扎并穿孔(CLP)造成腹腔感染，每日在麻醉下经胃管灌注大黄1次。分别在术前及术后24，48，72，96，120 h处死1组大鼠，检测肺毛细血管通透性、支气管肺泡灌洗液(BALF)的中性粒细胞百分率,分析血浆、肺组织和BALF的内毒素水平。结果：肺毛细血管通透性、BALF的中性粒细胞百分率及血浆、肺组织和BALF的内毒素含量逐渐增加，时间越长作用越明显。治疗组比感染组增加较慢、幅度较小。结论：大黄可阻止肺组织的内毒素含量和中性粒细胞数量的增加，减轻肺损伤。     

阻断内毒素胞内信号转导通路对大鼠移植肝脏再灌注损伤的影响

目的 探讨以白细胞介素-1受体相关激酶-4（IRAK-4）为靶点，阻断内毒素胞内信号转导后对大鼠移植肝脏再灌注损伤（I／RI）的影响并探索肝移植时可行的RNA干扰（RNAi）治疗途径。方法 两袖套法建立SD大鼠同种异体原位肝移植模型，随机分为冷缺血转染组、活体转染组及对照组。冷缺血转染组于冷缺血期经门静脉灌注转染携带IRAK-4-shRNA的质粒pSIIRAK-4；活体转染组在门静脉袖套吻合完成后，经门静脉分支注入pSIIRAK-4；对照组不予任何处理。按门静脉血流恢复后第0min、60min及180min分为三个亚组，RT—PCR及Western—blot测定肝组织的IRAK-4mRNA和蛋白表达水平；ELISA法测定受体血清TNF-α含量。采用TUNEL法检测肝细胞凋亡状态，透射电镜观察肝组织超微结构的病理形态学变化。结果 再灌注后冷缺血转染组的IRAK-4表达明显低于同时点的活体转染组及对照组（P〈0．01）；同时，肝细胞凋亡指数、血清TNF-α含量及肝细胞、血窦内皮细胞损伤程度也明显低于后者。结论 以IRAK-4为靶点的冷缺血期shRNAs转染途径能有效阻断内毒素胞内信号转导，进而减轻肝移植时的I／RI程度。     

动态浊度法定量检测氧氟沙星注射液中的内毒素

目的:对氧氟沙星注射液进行内毒素动态浊度法检查,建立定量检测氧氟沙星注射液中内毒素实验方法以代替热原检查法,提高内毒素的检出率。方法:采用《中国药典》2000年版附录检测内毒素的动态比浊法。结果:氧氟沙星注射液经2倍及以上倍数稀释后,对鲎试剂反应无干扰作用,内毒素回收率在50%～200%范围内。结论:本方法干扰因素小,检测结果准确,可作为日常检测使用。     

正交试验法优选D-氨基半乳糖敏化小鼠的内毒素休克模型

目的:建立D-氨基半乳糖敏化小鼠内毒素休克的规范化模型.方法:选择对内毒素休克小鼠死亡率有影响的3个因素:D-氨基半乳糖增敏剂量、内毒素攻击剂量及其给药途径,每个因素选取3个水平,按L9(34)正交试验表安排试验.以小鼠48 h死亡率为评价指标,并通过验证试验,优化与实验要求相符的造模条件.结果:各因素对动物死亡率影响程度依次为:D-氨基半乳糖增敏剂量＞内毒素给药途径＞内毒素攻击剂量.采用D-氨基半乳糖600 mg·kg-1敏化小鼠,腹腔注射内毒素0.5 mg·kg-1的给药方案为佳.结论:规范内毒素休克模型的复制条件,将有利于科学评价药物的抗内毒素活性.     

透析用水内毒素含量检测数据调查研究分析

目的符合透析治疗安全的透析用水是血液透析日常治疗开展的基本保障,根据统计分析内毒素含量的变化规律,探索控制透析用水内毒素含量的管理方式。方法对上海市21家血液净化中心(室)2019年3月至2020年2月期间透析用水的内毒素(endotoxin,ET)含量数据进行汇总与统计分析。结果透析用水内毒素含量在全年的春季与夏季中会存在部分偏高的情况,其中春季送检的样本中,ET含量>0.25 EU/ml比例占当季送检样本的0.57%,ET含量在0.03~0.25EU/ml之间的比例占7.34%;在夏季送检的样本中,ET含量>0.25EU/ml比例占当季送检样本的1.13%,ET含量在0.03~0.25EU/ml之间的比例占3.39%,与秋冬两季水平相比,差异有统计学意义(F=11.392,P值<0.001)。结论严格管控透析用水生产、输送过程的每个环节,规范采样流程、加强反渗机日常维护管理、重视水处理系统及配管的日常消毒等措施可减少血液透析相关的不良反应发生,提高患者透析质量。     

Amelioration of Endotoxin-Induced Uveitis in Rabbit by Topical Administration of Tacrolimus Proglycosome Nano-Vesicles

This work was aimed to improve the efficacy of tacrolimus in the treatment of endotoxin-induced uveitis (EIU) using propylene glycol modified lipid vesicles termed as proglycosome nano-vesicles (PNVs). PNVs were prepared by modified film hydration method. Experimental uveitis in rabbit eye was induced by an intravitreal injection of 20 μL of the endotoxin solution containing 100 ng of lipopolysaccharide endotoxin. In vivo efficacy of PNVs was determined by studying clinical symptoms of uveitis using slit lamp examination and by quantitatively measuring levels of tumor necrosis factor-alpha, interleukin-6, leukocytes and total proteins in aqueous humor, 24 h after intravitreal injection of endotoxin. Comparison was made with healthy, untreated and tacrolimus solution treated eyes. PNVs developed were nano-sized, deformable and showed sustained release of tacrolimus over period of 12 h. In vivo results indicated statistically significant difference between the effects of PNVs in the treatment of EIU compared to tacrolimus. PNV treatment not only subsides clinical symptoms of uveitis but also prevented breakdown of blood aqueous barrier. Tacrolimus loaded PNVs are potential new topical treatment for uveitis.     

一清胶囊在肺结核合并革兰阴性菌感染中的成本-效果分析

目的 对内毒素检测阳性的肺结核患者实施不同治疗策略,分析不同策略的成本-效果,为利用一清胶囊治疗革兰阴性菌(G)感染提供理论和经济学依据.方法 120例内毒素检测阳性的肺结核患者随机分为治疗组和对照组,治疗组同时接受一清胶囊联合常规的抗菌治疗,对照组仅进行常规的抗菌治疗.分别记录患者的CRP的复常时间、体温复常时间、内毒素转阴时间以及影像的感染情况改善程度进行成本-效果分析.结果 治疗组的CRP复常时间、体温复常时间和内毒素转阴时间均明显短于对照组.两组患者均未观察到空洞闭合,但治疗组47例患者的结核病灶有吸收好转(有效率78.3％)；对照组33例患者的结核病灶有吸收好转(有效率55.0％),两组比较差异有统计学意义(x2=4.97,P＜0.05).成本-效果分析表明对照组疗效较差且治疗成本明显偏高(P=0.013).结论 一清胶囊与常规抗菌治疗之间具有协同作用,能明显缩短病程和住院时间,两者联用成本效果更好,具有重要的经济价值.