Regulation of pro-inflammatory and anti-inflammatory cytokine responses by Kupffer cells in endotoxin-enhanced reperfusion injury after total hepatic ischemia

The effects of Kupffer cells on cytokine responses in endotoxin-enhanced reperfusion injury after total hepatic ischemia were investigated in this study. Male rats pretreated with either normal saline solution (NS group) or gadolinium chloride (GdCl(3)) to inhibit Kupffer cell function (GC group) were subjected to 60 min of hepatic ischemia. These animals received either normal saline solution or sublethal doses of endotoxin (1 mg/kg) at reperfusion. In the NS group, endotoxin administration induced an enhanced tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 production 1 h after reperfusion with a subsequent peak of macrophage inflammatory protein-2 (MIP-2) levels, which resulted in a 7-day survival rate of 30%. Despite endotoxin administration, GdCl(3) pretreatment significantly suppressed TNF-alpha and increased interleukin-10 production 1 h after reperfusion, which led to a decline in MIP-2 production and amelioration of functional and structural liver damage with a 7-day survival rate of 80%. Augmented pro-inflammatory and anti-inflammatory cytokine responses by Kupffer cells were associated with endotoxin-enhanced reperfusion injury after hepatic ischemia. Kupffer cell blockade has a potential to attenuate the insult via modulation of cytokine responses.     

Lack of endotoxin tolerance with respect to TNF alpha production in the subarachnoid space

To study endotoxin tolerance in the subarachnoid space 0.1 mg of endotoxin derived from Neisseria meningitidis was injected intracisternally into rabbits on 2 consecutive days. On day 1 the maximum peak level of TNF alpha was 7 ng/ml 2 h after injection, whereas on day 2 the highest levels were 3.6 ng/ml and 3.7 ng/ml, respectively, 1 and 2 h after injection. Pretreatment with intravenous endotoxin 5 or 21 h before consecutive intracisternal endotoxin did not affect the cerebrospinal fluid (CSF) levels of TNF alpha. In contrast, there was a marked endotoxin tolerance with respect to TNF alpha in the systemic circulation. Cells appearing in the CSF 5, 12 and 20 h after intracisternal injection of endotoxin were harvested, cultured, and then stimulated with 0.1 mg/ml of endotoxin. In 10 experiments a marked TNF alpha production in the range 10-70 ng/ml was detected in the supernatants, whereas unstimulated cells did not produce TNF alpha. We conclude that tolerance to endotoxin does not develop in the subarachnoid space as evaluated by the present experimental design. The pattern of TNF alpha production and endotoxin tolerance is distinctly different in the subarachnoid space and systemic circulation.     

人体胆汁内毒素测定及临床应用

本文探讨应用稀释法消除胆汁中抑制物质对鲎试验内毒素测定的影响。胆汁稀释后,用产色基质法按血浆内毒素定量原理测定,可获得较好结果。测定32例非胆系疾病胆囊胆汁内毒素浓度,平均为6.93±3.43ng/ml,最小一最大值为1.55—21.20ng/ml。     

心脉灵注射液对内毒素休克大鼠海马组织NOS活性的影响

采用尾静脉注射大肠杆菌内毒素复制大鼠内毒素休克模型，检测动物血压、脑系数、海马组织一氧化氮合酶（ＮＯＳ）活性及海马ＣＡ１区形态学改变，探讨心脉灵注射液对内毒素休克大鼠的作用机理。结果显示：与病理组相比，注入心脉灵注射液后１ｈ、６ｈ，动物血压上升，脑系数下降，海马组织ＮＯＳ活性显著增高，海马ＣＡ１区神经元损伤明显减轻，动物无死亡。提示心脉灵注射液能够改善内毒素休克所致的低血压及脑水肿，保护海马ＣＡ１区神经元，增强海马组织ＮＯＳ活性，起到抗内毒素休克的作用。     

清醒大鼠内毒素休克时血浆CGRP浓度及血管对CGRP反应性的改变

清醒大鼠静脉注射内毒素16.7mg/Kg后在血压、心率、血浆葡萄糖、乳酸浓度和肠道损伤等方面表现出典型的内毒素休克改变。在注射内毒素后30分钟与180分钟时血浆中降钙素基因相关肽(CGRP)的浓度显著增高,而腹主动脉对CGRP的反应性没有改变。血浆CGRP浓度的增高可能对内毒素休克的发生发展过程具有重要影响。     

内毒素血症细胞因子一氧化氮在重度失血性休克发展中的作用

目的　探讨内毒素血症、细胞因子、ＮＯ在重度失血性休克发展过程中的作用和机制。方法　选用大白兔２６只，分为失血性休克组（１４ 只），对照组（１２ 只），休克组观察休克前后血浆内毒素、ＴＮＦα、ＩＬ－ ６、ＩＬ－８、ＮＯ的动态变化，对照组观察手术前后上述指标的变化，两组动物均观察２４ 小时、４８ 小时存活率。结果　大白兔发生失血性休克后血浆内毒素、ＴＮＦα、ＩＬ－６、ＩＬ－８ 、ＮＯ的水平与休克前及对照组比较有明显升高，死亡动物中血浆上述物质水平显著高于存活动物。结论　内毒素血症、细胞因子、ＮＯ等发挥重要的协同作用，促使失血性休克向不可逆方向进展。     

Defining the Microbiological Quality of Dialysis Fluid

With increasing awareness about the degree and the potential impact of microbiological contamination in dialysis fluids, there is a desire to improve their microbiological quality. To achieve this goal, the origin of the microbiological contamination has to be identified. The water, the bicarbonate concentrate, and the fluid distribution system can be major contributors. Regular disinfection of the entire fluid path is necessary to prevent the formation of biofilm. The bicarbonate concentrate should be handled with special attention because it constitutes an excellent growth medium for microflora that may not be detected with regular assays. With a well maintained reverse osmosis (RO) system, frequent disinfection of the entire flow path, and microbiological awareness, it is possible to produce dialysis fluid that meets the most stringent standard (<10² colony forming units (CFU)/ml and <0.25 IU/ml of endotoxin). Adding a step of ultrafiltration just before the dialyzer can make the dialysis fluid ultrapure (<10⁻¹ CFU/ml and <0.03 IU/ml). One additional step of controlled ultrafiltration provides sterile and pyrogen-free fluids (<10⁻⁶ CFU/ml and <0.03 IU/ml) that can be used for infusion.     

内毒素休克狗心脏腺苷酸环化酶的改变

本实验在高度纯化的心肌肌膜观察到,狗注射内毒素后4小时,心脏基础腺苷酸环化酶及NaF、Gpp(NH)p、isoproterenol刺激的腺苷酸环化酶活性均明显降低。并对其机制进行了讨论。