Effect of etanercept on serum amyloid A protein (SAA) levels in patients with AA amyloidosis complicating inflammatory arthritis

We assessed changes in serum amyloid A protein (SAA) levels during treatment with etanercept in AA amyloidosis complicating inflammatory arthritis. Five women and four men with AA amyloidosis and inflammatory arthritis received etanercept. SAA levels were recorded before and after commencement of treatment. Previous immunosuppressive drugs included cyclophosphamide (four patients), azathioprine (three patients), methotrexate (two patients) and chlorambucil (in one patient). Two patients received no disease modifying drugs between the time of diagnosis of AA amyloidosis and commencement of etanercept. In seven out of nine patients the median SAA level during etanercept treatment was lower than levels before anti-tumour necrosis factor therapy. In five out of nine patients, the median post treatment level was <11 mg/l. There were no significant changes in serum creatinine or proteinuria during periods (median, 23 months; range, 1-24 months) of etanercept therapy. The etanercept was stopped in four patients because of: acute bacterial endocarditis, psoriasiform rash, psychosis and leukopenia. In two of these patients alternative biologics were commenced (adalimumab or anakinra) and one was restarted on etanercept. One patient died of cerebral haemorrhage during the study. Etanercept therapy was associated with a fall in SAA levels in seven of nine patients, five of whom achieved levels which might be expected to be associated with stable or regressing amyloid deposits. Etanercept represents a useful alternative to immunosuppressant therapy such as cyclophosphamide or chlorambucil. Further work is needed to establish whether organ damage related to AA amyloidosis is slowed by etanercept.     

Dietary habits, ethanol and tobacco consumption as predictive factors in the development of esophageal carcinoma in patients with head and neck neoplasms

SUMMARY.  Patients with primary head and neck cancers have a higher risk of developing esophageal cancer. The aim of this study was to investigate esophageal cancer prevalence, its risk factors (ethanol and tobacco consumption) and dietary habits in patients with head and neck cancer. Three hundred and twenty-six adults with primary head and neck cancer were followed by a retrospective observational study in a general university hospital in Sao Paulo, Brazil. Flexible videoendoscopy with lugol chromoscopy was the method used to investigate esophageal cancer prevalence. All subjects were interviewed face-to-face, revealing detailed information about their tobacco and alcohol use, as well as their dietary habits. Thirty-six patients with esophageal cancer were diagnosed and the overall prevalence rate was 11.04%. Patients who developed second esophageal tumors had the following characteristics: earlier age of initial ethanol consumption ( P  < 0.05), longer duration period of ethanol consumption ( P  < 0.05) and higher weekly consumption rate ( P  < 0.05). There was an increased risk of esophageal carcinoma in those patients who both smoked and drank ( P  < 0.05). There was no association between carcinoma of the esophagus and dietary habits in patients who developed esophageal neoplasms, compared with those who did not. Prevalence rate of esophageal neoplasms was 11.04% in patients with head and neck carcinoma, whose ethanol consumption was associated with esophageal cancer. There was an increased risk between ethanol and tobacco consumption and esophageal carcinoma development. On the other hand, there was no association regarding dietary habits between patients who developed esophageal cancer and those who did not.     

经桡动脉与经股动脉两种途径冠心病介入治疗的对比研究

目的 :比较经桡动脉途径和股动脉途径冠心病介入的手术方法、结果和并发症。方法 :10 3 3例冠心病住院患者分别接受经桡动脉 （ A）组 （ n=419）或经股动脉 （ F）组 （ n=614 ）途径的冠心病介入 （ PCI）治疗 ,观察两组手术成功率和并发症发生率。结果 :两组患者 PCI成功率没有显著性差异。A组局部血肿、不适反应等发生率显著低于 F组 ,假性动脉瘤、动静脉瘘、局部感染及表皮坏死等并发症在 A组未出现 ,F组分别发生 11,4,6,7例 ,但两组间无显著性差异。两组均未出现远端肢体缺血、神经损伤等。结论 :实施 PCI术的两种途径都是安全、有效和可行的方法 ,与经股动脉比较 ,经桡动脉途径可减少并发症的发生     

骨髓增生异常综合征T细胞早期激活及可溶性肿瘤坏死因子受体的研究

目的　研究骨髓增生异常综合征 (MDS)外周血CD+ 4 、CD+ 8T细胞早期激活标志CD69的表达及血清、骨髓可溶性肿瘤坏死因子受体 1、2 (sTNF R1、2 )的水平及其意义。方法　在植物血凝素 (PHA) 2 0mg/L条件下进行全血细胞培养 ,于 0h和 4h分别用流式细胞仪对CD+ 4 、CD+ 8T细胞CD69的表达进行分析。用ELISA法检测血清和骨髓sTNF R1、2的水平。结果　PHA刺激前难治性贫血 (RA)与难治性贫血伴环形铁粒幼细胞增多 (RAS)CD+ 4 、CD+ 8细胞CD69的表达率分别为 8 32 %、9 88% ,难治性贫血伴原始细胞增多 (RAEB)与转变中的RAEB(RAEB T)CD+ 8细胞CD69的表达率为7 92 %。PHA刺激后MDS患者CD+ 4 、CD+ 8细胞表达CD69明显增强 ,RA +RAS为 5 3 4 6 %、5 1 6 3% ;RAEB +RAEB T为 4 2 93%、4 1 96 % ,CD+ 4 与CD+ 8细胞CD69的表达率相似。MDS两种sTNF R1水平均明显升高 ,RA +RAS组sTNF R1血清为 (1 5 8± 0 6 8) μg/L ,骨髓为 (2 10± 0 2 6 ) μg/L ;sTNF R2血清为 (1 4 1± 0 5 0 ) μg/L ,骨髓为 (1 95± 0 6 4 ) μg/L ;RAEB +RAEB T组sTNF R1血清为 (2 6 2± 2 5 5 ) μg/L ,骨髓为 (3 12± 0 6 7) μg/L ;sTNF R2血清为 (1 96± 0 5 6 ) μg/L ,骨髓为(3 0 9± 0 6 2 ) μg/L。血清sTNF R2水平与PHA刺激     

Transforming growth factor-β receptor antagonism attenuates myocardial fibrosis in mice with cardiac-restricted overexpression of tumor necrosis factor

The mechanisms that are responsible for the development of myocardial fibrosis in inflammatory cardiomyopathy are unknown. We have previously generated lines of transgenic mice with cardiac-restricted overexpression of tumor necrosis factor (MHCsTNF mice), a pro-inflammatory cytokine. The MHCsTNF mice develop a heart failure phenotype that is characterized by progressive myocardial fibrosis, as well as increased levels transforming growth factor-β (TGF-β)(mRNA and protein. In order to determine whether TGF-β-mediated signaling was responsible for the myocardial fibrosis observed in the MHCsTNF mice, we treated MHCsTNF and littermate control mice from 4 to 12 weeks of age with a novel orally available TGF-β receptor antagonist (NP-40208). At the time of terminal study, myocardial collagen content was determined using the picrosirius red technique, and left ventricular (LV) systolic and diastolic function were determined using the Langendorff method. Treatment with NP-40208 resulted in a significant (P < 0.05) 65% decrease in nuclear translocation of Smad 2/3, a significant (P < 0.05), decrease in the heart-weight to body-weight ratio from 6.5 to 5.7, a ∼37% decrease in fibrillar collagen content (P < 0.01) and a significant (P < 0.05) decrease in the LV chamber stiffness by ∼25% in the MHCsTNF mice when compared to diluent-treated controls. Treatment with NP-40208 had no discernable effect on LV systolic function, nor any effect on cardiac myocyte size or fetal gene expression in the MHCsTNF mice. Taken together, these observations suggest that sustained pro-inflammatory signaling in the adult heart is associated with a pro-fibrotic phenotype that arises, at least in part, from TGF-β-mediated signaling, with resultant activation of Smad 2/3, leading to increased myocardial fibrosis and increased LV diastolic chamber stiffness. Returned for 1. revision: 29 August 2007 1. Revision received: 24 September 2007     

Expression of interleukin-1beta and tumour necrosis factor-alpha in plasma cells from patients with multiple myeloma

Interleukin-1beta(IL-1beta) and tumour necrosis factor-alpha (TNF-alpha) are potent bone resorbing cytokines that may contribute to the development of the osteolytic bone disease observed in patients with multiple myeloma (MM). Although these factors have been identified in cultures of bone marrow mononuclear cells isolated from patients, the identity of the cells responsible for producing IL-1beta and TNFalpha remains unclear. Using a sensitive dual-colour fluorescence in situ hybridization (FISH) technique and a two-colour immunofluorescence method we have investigated the expression of the mRNA and protein, for IL-1beta and TNFalpha, by individual bone marrow plasma cells from patients with MM and monoclonal gammopathy of undetermined significance (MGUS). The mRNA for IL-1beta and TNFalpha was identified in all cells expressing the immunoglobulin light chain from all patients with MM and MGUS. However, the IL-1beta protein could not be detected in cytoplasmic light chain positive cells in any of the patients examined. In contrast, the TNFalpha protein was detected in clonal plasma cells from patients with both MM and MGUS. Interestingly, the IL-1beta and TNFalpha mRNA and proteins were readily detected within a small proportion of the non-plasma cells from patients with both MM and MGUS. These data suggest that myeloma cells in vivo are able to produce TNFalpha but not IL-1beta. In addition, a small proportion of accessory cells are likely to be able to contribute to the production of both ILbeta and TNFalpha.     

脂联素对刀豆球蛋白A诱导小鼠免疫性肝损伤的保护作用

目的探讨脂联素(ADPN)是否对肝脏的免疫性损伤具有保护作用以及可能的作用机制。方法将小鼠ADPN基因高效表达载体导入小鼠体内,获得高血清ADPN模型小鼠(表达载体组),与导入空载体的对照小鼠(空载体组)同时静脉内注射刀豆球蛋白A(Con A),以诱导肝脏的免疫性损伤,测定不同时间点血清ALT浓度,并进行肝组织病理学检查(HE染色),观察两组小鼠肝脏损伤程度是否有差异。比较两组间血清TNFα浓度的不同,探讨可能的作用机制。结果表达载体组小鼠注射Con A后血清ALT水平的升高明显低于空载体组,差异有统计学意义(P<0.01),组织学检查也显示表达载体组小鼠的肝损伤明显低于空载体组。经统计分析表明,ALT水平与血清ADPN水平成负相关(r=-0.5034,P=0.0121)。表达组小鼠血清TNFα水平明显低于空载体组(P<0.01)。结论脂联素对Con A诱导的肝脏免疫性损伤具有保护作用,其作用机制可能与抑制TNFα的产生进而阻断肝细胞遭受免疫性攻击有关。     

重组腺相关病毒介导的细胞色素P450表氧化酶基因对TNF-α诱导人脐静脉内皮细胞炎症的影响

目的研究过度表达细胞色素P450表氧化酶基因引起内源性EETs产生增加是否能抑制由TNF—α诱导的内皮炎症。方法以携带三种不同表氧化酶基因的重组腺相关病毒rAAV- CYP2C11、rAAV—CYP2J2和rAAV—CYPF87V转染人脐静脉内皮细胞,然后再以TNF—α干预,来研究它们对内皮VCAM-1的表达及外周血单核细胞PBMC与内皮细胞粘附的影响。结果TNF-α诱导了 HUVEC中VCAM-1蛋白质的表达,rAAV—CYP2C11、rAAV—CYP2J2能明显抑制TNF-α的这一作用。 TNF-α诱导了PBMC与HUVEC的粘附(100±0．0％ vs 620．1±65．3％),rAAV-CYP2C11、rAAV- CYP2J2能明显抑制TNF-α的这一作用(分别为120．3±33．4％ vs 387．7±27．4％．131．0±28．7％ vs 535．0±69．7％)。结论CYP2C11和CYP2J2基因具有显著的保护内皮细胞、对抗炎症介质介导的内皮损伤的作用。     

基质金属蛋白酶在阻塞性肺气肿大鼠模型中的表达及部分细胞因子的水平

目的　观察基质金属蛋白酶 2 (MMP 2 )和MMP 9在阻塞性肺气肿大鼠模型中的表达及白细胞介素 (IL) 1 0和肿瘤坏死因子 (TNF)α的水平。方法　 2 4只雄性Wistar大鼠随机分为 2组 ,每组1 2只 ,阻塞性肺气肿模型组 :将大鼠置于自制有机玻璃染毒箱内进行被动吸烟 (金键牌香烟 ) ,每天 2次 ,每次 1 6支 ,持续 30min ,2次之间间隔 4h ,连续 75d。健康对照组大鼠 2级实验动物房内室温常规饲养。 2组大鼠行第 0 3秒钟用力呼气容积 (FEV0 3)、FEV0 3/用力肺活量 (FVC)、功能残气量 (FRC)的测定。大鼠处死后 ,行支气管肺泡灌洗 ,测支气管肺泡灌洗液 (BALF)中白细胞总数和各分类细胞数、MMP 2和MMP 9的活性及IL 1 0和TNFα的含量。免疫组化法检测支气管、肺组织中MMP 2和MMP 9的表达及其蛋白相对含量。Weigert弹力纤维染色观察弹力纤维的变化。结果　阻塞性肺气肿模型组大鼠支气管黏膜上皮大片脱落 ,管壁及周围大量的单核细胞和淋巴细胞浸润 ;肺泡结构紊乱 ,肺泡壁变薄或断裂 ,肺泡弹性减弱 ,呈囊状扩张 ,肺泡腔扩大 ,部分融合成肺大疱。与健康对照组相比 ,阻塞性肺气肿模型组大鼠FEV0 3[(5 1 2± 0 42 )ml]、(FEV0 3/FVC)× 1 0 0 % [(71 1 5± 9 84) ]显著降低 ,FRC[(7 2 2± 2 1 8)ml]显著增加 (P值均 <     

Aeroportia and acute abdominal pain: ischemic bowel necrosis

Pneumatosis intestinalis and aeroportia are typical findings of mesenteric ischemia. The second carries a worse prognosis than the former. We report the case of a patient presenting with acute abdominal pain and acidosis after admission to the coronary unit for myocardial infarction. An emergent abdominal CT scan showed aeroportia. Laparotomy confirmed extended bowel necrosis. Aeroportia is a typical feature of ischemic bowel necrosis, often associated with advanced disease and bad prognosis. In the presence of acute abdominal pain, aeroportia should be considered as a sign of ischemic bowel necrosis. Emergent laparotomy is warranted.