肺动脉灌注低温保护液减轻体外循环肺内炎性反应

目的　研究肺动脉灌注低温保护液减轻体外循环肺内炎性反应的作用。方法　 4 0例行法洛四联症 (TOF)根治术的病儿随机分为肺保护组 2 0例 ,对照组 2 0例。肺保护组体外循环期间肺动脉灌注低温肺保护液 ,对照组行常规TOF根治术。围手术期监测血浆肿瘤坏死因子 (TNF α)水平。收集术后6h气管吸出物 ,检测其中炎性介质白细胞介素 (IL) 6、IL 8水平。征得病儿家属同意 ,术后取右下肺组织活检 ,观察组织内炎性反应情况。同时监测围手术期肺功能及临床指标。结果　肺保护组血浆中TNF α水平低于对照组 ,以回ICU 0h、2 4h差异显著 (P <0 0 1、P <0 0 5 ) ;术后 6h内气管吸出物中IL 6和IL 8水平肺保护组低于对照组 (P <0 0 1) ;肺组织活检对照组可见中性粒细胞浸润 ,肺保护组无明显病理改变。肺保护组术后肺泡 -动脉氧分压差 (A aO2 )较对照组低 ,以回ICU 0h、12h和 2 4h差异显著(P <0 0 5、P <0 0 1和P <0 0 5 ) ;肺保护组呼吸机辅助通气时间短于对照组 (P <0 0 1)。结论　肺动脉灌注低温保护液可明显减轻体外循环中肺内的炎性反应和改善肺功能。     

Drosera rotundifolia and Drosera tokaiensis suppress the activation of HMC-1 human mast cells

Ethnopharmacological relevance

Several Northern Hemisphere Drosera species have been used in the therapy of respiratory tract infections as the traditional medicine Droserae Herba.

Aim of the study

To determine the anti-inflammatory effects of Drosera species and to investigate a substitute material for Droserae Herba, we examined the effect of extracts of Drosera rotundifolia, Drosera tokaiensis and Drosera spatulata on activated T cell membrane (aTc-m)-induced inflammatory gene expression in HMC-1 human mast cells.

Materials and methods

Drosera rotundifolia, Drosera spatulata and Drosera tokaiensis were collected in Japan. Herbs were extracted with 80% EtOH, and subsequently applied to OASIS HLB column. HMC-1 cells were treated with each Drosera column-adsorbed fraction for 15 min, and subsequently added to aTc-m and incubated for 16 h. Inflammatory gene and protein expressions were determined by DNA microarray, RT-PCR and Western blotting.

Results

Drosera rotundifolia and Drosera tokaiensis fractions, but not the Drosera spatulata fraction, suppressed inflammatory gene expression induced by aTc-m in HMC-1 cells.

Conclusions

Drosera rotundifolia and Drosera tokaiensis suppressed activation of HMC-1 cells induced by aTc-m. Since the Drosera tokaiensis fraction was more effective than the traditionally used Drosera rotundifolia, Drosera tokaiensis is a likely substitute as a source of Droserae Herba.     

Interleukin-18 Affects Local Cytokine Expression But Does Not Impact on the Development of Kidney Allograft Rejection

Interleukin-18 is predominantly a macrophage-derived cytokine with a key role in inflammation and cell-mediated immunity. Having previously demonstrated IL-18 upregulation in a rat model of kidney rejection, here we examined IL-18 in a fully MHC-mismatched murine model of acute kidney rejection using IL-18-deficient recipients (IL-18-/-) and animals administered neutralizing IL-18 binding protein (IL-18BP). Gene expression of IL-18 and its receptor were significantly upregulated in allografts compared to isografts, as was the cellular infiltrate (T cells and macrophages) (p < 0.001). Allografts developed kidney dysfunction (p < 0.05) and tubulitis (p < 0.01) not observed in controls. There was a significant reduction in gene expression of IL-18 downstream pro-inflammatory molecules (iNOS, TNFalpha and IFNgamma) in IL-18-/- recipients (p < 0.01), and IL-18BP-treated animals. The CD4+ infiltrate and IL-4 mRNA expression was greater in the IL-18-/- recipients than wild-type (WT) allografts and IL-18BP-treated animals (p < 0.05), suggesting a Th2-bias which was supported by IFNgamma and IL-4 ELISPOT data and an increased eosinophil accumulation (p < 0.001). Neither IL-18 deficiency nor neutralization prevented renal dysfunction or tubulitis. This study demonstrates increased production of IL-18 in murine kidney allograft rejection and provides evidence that IL-18-induced pathways of inflammation are active. However, neither IL-18 deficiency nor neutralization was protective against the development of allograft rejection.     

原发性高血压患者的亚临床炎症状态

目的　探讨炎症与原发性高血压之间的关系。方法　采用超敏感的方法检测血清超敏感C反应蛋白 (hsCRP)水平 ,采用ELISA法检血清肿瘤坏死因子 (TNF) α、白介素 (IL) 6水平 ,比较 6 0例正常人 (对照组 )及 10 9例原发性高血压患者 (病例组 )之间炎症标志水平的差异 ,分析炎症标志与原发性高血压患者各临床指标之间的关系。结果　对照组血清hsCRP浓度为 0 .18～ 4 .14mg/L ,中位数为 0 .6 2mg/L ;病例组为 0 .18～2 2 .0 0mg/L ,中位数为 1.17mg/L ,病例组显著高于对照组 (P <0 .0 5 )。病例组中 ,hsCRP水平与收缩压 (SBP)、体重指数 (BMI)、腰臀比 (WHR)、空腹胰岛素 (FI)、胰岛素抵抗指数 (HOMA IR)等临床指标均呈等级相关性 (P<0 .0 5 ) ,以hsCRP作为应变量 ,以相关临床指标作为自变量 ,进行多元回归分析 ,BMI、SBP进入方程。高血压病患者的炎症细胞因子TNF α、IL 6均与BMI相关 (r值分别为 0 .2 2 0、0 .2 2 9,P <0 .0 5 ) ,IL 6与SBP显著相关 (r =0 .2 34,P <0 .0 5 )。结论　原发性高血压患者存在亚临床炎症状态 ,SBP增高及肥胖是可能的促进炎症因素。     

Clinical evaluation of technetium-99m infecton for the localisation of bacterial infection

The aim of the study was to distinguish infection from inflammation in patients with suspected infection using technetium-99m Infecton. Ninety-nine patients (102 studies) referred for infection evaluation underwent imaging with 400 MBq^99mTc-Infecton at 1 and 4 h. Most patients had appropriate microbiological tests and about half (56) had radiolabelled white cell scans as well. No adverse effects were noted in any patient. The clinical efficacy of^99mTc-Infecton depended in part on whether imaging was undertaken during intibiotic therapy for infection or not. In consultation with the microbiologist, 5–14 days of appropriate and successful antibiotic therapy was considered adequate to classify some results as true-negatives. The figures for sensitivity and specificity of^99mTc-Infecton for active or unsuccessfully treated infection were 83% and 91% respectively. It is concluded that^99mTc-Infecton imaging contributed to the differential diagnosis of inflammation. It is being used as the first imaging modality when bacterial infection is suspected.     

高容量血液滤过治疗多器官功能障碍综合征的分析

目的研究高容量血液滤过 (HVHF)在多器官功能障碍综合征 (MODS)治疗中的作用。方法 19例MODS患者 ,随机选择 10例行HVHF ,另 9例行常规连续性静脉 静脉血液滤过 (CVVH)。于治疗前和治疗开始后 2、4、8h动脉采血 ,检测血气、血肌酐 (Scr)、尿素氮 (BUN)、肿瘤坏死因子(TNFα)、白细胞介素 1(IL 1β)、白细胞介素 6 (IL 6 )的变化。 结果HVHF组与CVVH组于治疗开始后4h血Scr、BUN均显著下降 ,肾功能改善。HVHF组血TNFα、IL 1β、IL 6治疗前分别为 ( 1795± 5 0 6 )ng/L、( 96 4± 185 )ng/L、( 1332± 4 15 )ng/L ,治疗开始后 4h为 ( 12 6 5± 397)ng/L、( 5 11± 12 4 )ng/L、( 72 6±2 4 3)ng/L ,差异有显著意义 ,P <0 0 5。CVVH组血TNFα治疗前为 ( 1799± 5 11)ng/L ,治疗开始后 4h为 ( 132 7± 4 2 1)ng/L ,差异有显著意义 ,P <0 0 5。HVHF组死亡 3例 ( 3/ 10 ) ,CVVH组死亡 5例 ( 5 / 9) ,差异有显著意义 ,P <0 0 5。结论HVHF可通过对流和AN6 9膜的吸附作用清除大量炎症介质 ,改善MODS患者的预后     

转化生长因子-β在哮喘气道炎症与重塑中的作用

Transforming growth factor-β(TGF-β) was reported to be increased in asthma in some studies. Accumulation of TGF-β in airway promotes smooth muscle cell mitogenesis and hyperplasia, and in-duces fibroblast and myofibroblast and smooth muscle proliferation as well as increase in protein synthesis in connective tissue(such as collagen deposition on the reticular basement membrane). The autocrine induction of collagen expression by smooth muscle may contribute to the thickening of the reticular basement membrane, irre-versible f‘throsis and remodeling seen in the airways in some asthmatics. TGF-β is considered to be a major fi-brogenic cytokine. It can increase smooth muscle mass and lead to severe bronchial obstruction in an asthma at-tack.     

Selective localisation of neuro-specific T lymphocytes in the central nervous system

Using experimental autoimmune encephalomyelitis (EAE) in the rat as a model of central nervous system (CNS) inflammation, activated and quiescent T lymphocytes with different antigen specificities were labelled with the fluorescent dye Hoechst 33342 and tested by fluorescence microscopy for their ability to accumulate in different regions of the spinal cord and in other organs at varying times post inoculation. With this highly sensitive assay it was found that activated myelin basic protein (MBP)-specific T cell lines accumulated in the spinal cord (a 1000-fold increase in the lumbar/sacral region by day 4) and caused clinical signs of EAE. In contrast, interleukin-2 (IL-2)-maintained (quiescent) MBP-specific T cell lines failed to accumulate in the CNS and cause disease. Activated ovalbumin (OA)-specific and purified protein derivative of tuberculin (PPD)-specific T cell lines were also found at significantly higher levels in the spinal cord than non-activated cells although they failed to accumulate to a substantial degree when injected alone. When injected with activated MBP-specific T cells the activated OA- and PPD-specific cell lines accumulated in the spinal cord following initial accumulation of the MBP-specific cells, demonstrating that during the inflammatory process there is considerable non-specific recruitment of cells into the inflammatory site. CNS accumulation of activated MBP-specific T cell lines occurred 1-2 days later in irradiated animals than in non-irradiated recipients. This was consistent with irradiated animals also exhibiting a later onset of disease and suggests that irradiation may directly affect the endothelium in a way that makes it less adhesive. In conclusion, this study demonstrates that activated lymphocytes of any specificity enter the spinal cord, and that the neuro-antigen specific cells accumulate there and lead to the recruitment of other cells. Non-activated cells, even those with neural antigen specificity fail to enter the cord. Understanding the nature of what an 'activated' lymphocyte is may allow us to design strategies to inhibit such immune-mediated inflammation.     

Apolipoprotein E4 enhances brain inflammation by modulation of the NF-κB signaling cascade

Apolipoprotein E4 (apoE4), the major genetic risk factor of Alzheimer's disease (AD), is associated with enhanced brain inflammation. Genome-wide gene expression profiling was employed to study the effects of apoE genotype on hippocampal gene expression in LPS-treated mice, transgenic for either apoE4 or the AD benign allele, apoE3. This revealed that the expression of inflammation-related genes following intracerebroventricular injection of LPS was significantly higher and more prolonged in apoE4 than in apoE3 transgenic mice. Clustering analysis revealed gene clusters which responded differently in apoE4 and apoE3 mice and were significantly enriched in NF-kappaB response elements. Direct measurement of NF-kappaB-regulated genes revealed that their extent of activation was greater in the apoE4 mice. Immunohistochemistry experiments revealed that microglial and NF-kappaB activation were more pronounced in apoE4 than in apoE3 mice. These findings suggest that the increased brain inflammation in apoE4 mice is related to disregulation of NF-kappaB signaling pathway.