Predominant pathogenic role of tumor necrosis factor in experimental colitis in mice

Antibodies to tumor necrosis factor (TNF)-α have been recently proposed as effective treatment for patients with Crohn's disease. Here, we analyze the functional role of TNF-α in a mouse model of chronic intestinal inflammation induced by the hapten reagent 2,4,6,-trinitrobenzene sulfonic acid (TNBS) that mimics some characteristics of Crohn's disease in humans. Macrophage-enriched lamina propria (LP) mononuclear cells from mice with TNBS-induced colitis produced 10–30-fold higher levels of TNF-α mRNA and protein than cells from control mice. When mice with chronic colitis were treated by intraperitoneal injection of antibodies to TNF-α, an improvement of both the clinical and histopathologic signs of disease was found. Isolated macrophage-enriched LP cells from anti-TNF-α-treated mice produced strikingly less pro-inflammatory cytokines such as interleukin (IL)-1 and IL-6 in cell culture. The predominant role of TNF-α in the mouse TNBS-induced colitis model was further underlined by the finding that striking colonic inflammation and lethal pancolitis was induced in TNF-α-transgenic mice upon TNBS treatment. Conversely, no significant TNBS-induced colitis could be induced in mice in which the TNF-α gene had been inactivated by homologous recombination. Complementation of TNF-α function in TNF^?/? mice by the expression of a mouse TNF-α transgene was sufficient to reverse this effect. Taken together, the data provide direct evidence for a predominant role of TNF-α in a mouse model of chronic intestinal inflammation and encourage further clinical trials with antibodies to TNF-α for the treatment of patients with Crohn's disease.     

Pathology of a new Toxic Syndrome caused by ingestion of adulterated oil in Spain

Summary The Toxic Syndrome (TS) caused by ingestion of adulterated rapeseed oil in Spain is a new disease of multisystemic character whose aetiology and pathogenesis remains unknown. The most prominent pathological feature is a peculiar non-necrotizing vasculitis, that affects mainly the intima and involves vessels of every type and size in practically every organ. The TS begins with an acute clinical picture with pleuropneumopathy, fever, headaches, exanthems and eosinophilia. In these early clinical phases the main pathological findings were observed in the lungs and consisted of intense pulmonary interstitial oedema with scanty inflammatory mononuclear infiltrates. Ultrastructural study revealed hydropic degeneration of pneumocytes types I and II with desquamation of type I. The patients in this phase died of respiratory failure, later deaths were due to thromboembolic complications. Later still the patients developped a neuromuscular syndrome, sclerodermiform skin lesions and severe weight loss and died predominantly of infectious complications and respiratory failure. The anatomopathological picture in the peripheral nerves was that of inflammatory neuropathy with a lymphocytic perineuritis that led to perineural fibrosis with secondary axonal degeneration. The muscle presented an interstitial inflammatory myopathy at first followed by a neurogenic muscular atrophy. The skin lesions in the late phases consisted in dermal or dermal and subdermal fibrosclerosis, with vasculitis of the small arteries in the lower dermis. The salivary glands and pancreas showed vasculitis and interstitial inflammation which progressed to interstitial fibrosis and parenchymal atrophy.     

IL-10 Secretion and Sensitivity in Normal Human Intestine and Inflammatory Bowel Disease

Interleukin-10 (IL-10) deficiency in gene knockout mice causes chronic enterocolitis. We hypothesized that inflammation in human inflammatory bowel disease might result from innate alterations in the IL-10 pathway. Serum, supernatants, and mRNA of peripheral blood mononuclear cells (PBMC) and lamina propria mononuclear cells (LPMC) derived from inflamed (LPMC-i) and noninflamed colonic mucosa (LPMC-ni) were collected from patients with Crohn's colitis, ulcerative colitis, and controls. IL-10 protein concentrations and IL-10 mRNA were examined in response to PMA/CD3 or PHA stimulation. The response to rhIL-10 was assessed by inhibition of tumor necrosis factor-alpha (TNF-), IL-6, and interferon-gamma (IFN-) production. Serum IL-10 levels of inflammatory bowel disease (IBD) patients were within the normal range. IL-10 concentrations in supernatants from LPMC-i were significantly lower than from LPMC-ni or PBMC. No difference was seen between samples from ulcerative colitis and Crohn's disease. IL-10 mRNA was detected in 0/4 LPMC-i samples compared to 1/6 LPMC-ni and 6/6 PBMC. RhIL-10 inhibited TNF-, IL-6, and IFN- synthesis in PBMC. This effect was strongly diminished in LPMC. Disease-specific alterations were not detected. Our data suggest that LPMC derived from inflamed colonic mucosa have a reduced ability to produce and to respond to rhIL-10. A disease-specific alteration in the IL-10 pathway, however, was not found.     

放射性皮肤损伤机制的研究进展

皮肤是人体受到电离辐射时最先接触的器官,因其基底细胞层及毛细血管对射线很敏感,所以放射性皮肤损伤十分常见,急性放射性皮肤损伤常与表皮和真皮中的细胞改变和炎症有关,而皮肤的晚期损伤主要与辐射对血管影响有关。放射性皮肤损伤的临床表现为皮肤黏膜出现红斑、干性脱屑、湿性脱屑、溃疡,严重程度与射线种类、剂量等相关。目前,放射性皮肤损伤的潜在发生机制在很大程度上是未知的,辐射损伤后还未建立治疗的金标准,已知的放射性皮肤损伤的发生机制大致可分为3个途径：活性氧大量增加引发的氧化应激损伤、细胞因子被转录激活后引发的炎症、骨髓源性细胞引起的免疫反应。本文综述了放射性皮肤损伤发生机制的3大途径,为进一步研究放射性皮肤损伤的机制以及预防治疗提供参考。     

慢阻肺合并肺动脉高压患者机体炎性反应与肺阻力的相关性

目的:观察慢阻肺合并肺动脉高压患者机体炎性反应指标及与肺阻力相关指标表达,分析患者炎性反应与肺阻力的相关性。方法:回顾性选取医院收治的116例慢阻肺患者病历资料,根据患者是否合并肺动脉高压将其分为非肺动脉高压组(59例)和肺动脉高压组(57例)。抽取两组患者清晨空腹静脉血,检测炎性反应指标中的C反应蛋白(CRP)、白细胞计数(WBC)、降钙素原(PCT)、白细胞介素-6(IL-6)以及血沉(ESR),并进行对比;检测两组患者肺阻力指标振荡频率5 Hz下的气道粘性阻力实测值占预计值的百分比[R_5占预计值(%)]、振荡频率5 Hz与共振频率(Fres)之间电抗X曲线下面积(AX),振荡频率在5 Hz的肺弹性阻力(X₅),并进行对比。分析炎性反应相关指标与肺阻力指标的相关性。结果:肺动脉高压组CRP、WBC、PCT及IL-6水平均高于非肺动脉高压组,ESR低于非肺动脉高压组,差异有统计学意义(t=16.243,t=12.413,t=6.726,t=32.670,t=10.102;P<0.05);肺动脉高压组R5占预计值(%)、AX及X₅均高于非肺动脉高压组,差异有统计学意义(t=19.770,t=8.230,t=19.685;P<0.05);相关检验结果显示,慢阻肺合并肺动脉高压患者CRP、WBC、PCT及IL-6水平与R_5占预计值%、AX及X₅值呈正相关,ESR水平与R_5占预计值%、AX及X₅值呈负相关。结论:慢阻肺合并肺动脉高压患者常伴不同程度的炎性反应与肺阻力,且炎性反应程度与患者肺阻力间呈明显相关性,炎性因子检测可能对评估慢阻肺合并肺动脉高压患者的肺阻力情况有一定价值,可指导临床诊治。     

炎症性肠病患者巨细胞病毒感染危险因素

目的探讨炎症性肠病(IBD)患者巨细胞病毒(CMV)感染危险因素及CMV包膜糖蛋白H(gH)基因分型与临床疗效的关系。方法选取2015年2月-2019年12月河北北方学院附属第一医院收治的IBD患者362例,调查CMV感染情况以及临床疗效,多因素Logistic回归分析IBD患者合并CMV感染的危险因素,分析感染不同CMV gH基因型IBD患者临床特点及临床治疗效果。结果362例IBD患者中CMV感染患者122例,CMV感染率为33.70%,单因素分析结果显示,年龄≥40岁、重度IBD病情、广泛结肠型病变范围、糖皮质激素治疗、免疫抑制剂治疗、抗病毒治疗、激素依赖、结肠切除、临床治疗无效是IBD患者CMV感染的危险因素(P<0.05);多因素Logistic回归分析显示年龄≥40岁、重度IBD病情、广泛结肠型病变范围、糖皮质激素治疗、免疫抑制剂治疗是IBD患者CMV感染的独立危险因素;122例IBD合并CMV感染患者中gH 1型85例(69.67%)、gH 2型37例(30.33%);gH 1型与gH 2型IBD合并CMV感染患者的年龄≥40岁、广泛结肠型病变范围、糖皮质激素治疗、免疫抑制剂治疗、结肠切除结局以及激素依赖占比比较差异无统计学意义,而gH 1型患者病情严重程度比较差异有统计学意义(P<0.05),gH 1型与gH 2型患者的治疗有效率比较差异无统计学意义(χ²=0.017,P=0.895)。结论年龄≥40岁、重度病程、广泛结肠病变、糖皮质激素以及免疫抑制剂治疗会增加IBD患者CMV感染风险,IBD并CMV患者以gH1型为主,但gH基因分型不会影响临床疗效。     

侵袭性牙周炎患者疱疹病毒感染和外周血病毒载量

目的分析不同严重程度侵袭性牙周炎(AGP)患者疱疹病毒(HV)感染情况和外周血病毒载量。方法选取2014年12月-2019年12月济南市市中区人民医院口腔科收治的2600例AGP患者,根据病变程度分为轻度AGP组(n=82)、中度AGP组(n=578)、重度AGP组(n=1940),以同期100名健康人群为对照组。入组后,检测龈沟液HV病毒感染情况和血浆单纯疱疹病毒1型(HSV-1)、EB病毒(EBV)、人类巨细胞病毒(HCMV)、人类疱疹病毒6型(HHV-6)载量、牙周特征和血炎症因子水平。结果AGP患者牙周菌斑指数(PLI)、探诊深度(PD)、附着丧失(AL)、出血指数(BI)高于对照组(P<0.05),HSV-1、EBV、HCMV、HHV-6感染率和病毒载量高于对照组(P<0.05),白细胞(WBC)、降钙素原(PCT)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、C-反应蛋白(CRP)高于对照组(P<0.05);随着AGP病情严重程度增加,HSV-1、EBV、HCMV、HHV-6感染率和病毒载量、PLI、PD、AL、BI、WBC、PCT、IL-6、TNF-α和CRP均增加(P<0.05)。结论HV感染率和病毒载量与AGP患者血清炎症因子水平和牙周特征随病情严重程度增加而升高。     

肿瘤标记物CA_(125)、CA_(153)、CA_(199)与CEA在肺癌诊断中的意义

目的 :研究四种肿瘤标记物CA12 5、CA153 、CA199与CEA在肺癌诊断中的意义 ,并以常见的几种呼吸道炎症性疾病 (RIDs)作为对照。结果 :肺癌患者CA12 5、CA153 、CA199及CEA水平均显著高于RIDs患者 (P <0 .0 0 1) ,而CA12 5、CA153 、CA199及CEA水平在肺癌的三种组织学类型和各期肺癌中并显著性差异 (P >0 .0 5 )。采有四项指标的平均值作为标准 ,虽然并不能显著提高诊断的灵敏度 (P >0 .0 5 ) ,但可显著提高诊断的特异性 (P <0 .0 5或 0 .0 1)。结论 :CA12 5、CA153 、CA199及CEA可作为肺癌的标记物 ,检测这四项标记物在临床上具有一定的辅助意义     

术前孤立性CRP升高与体外循环术后并发症的相关性

目的探讨无感染的、术前孤立性C-反应蛋白(CRP)增加,对于体外循环心脏术后的结果,是否有预测性价值。方法分术前孤立性CRP升高(10.5～70.2mg／L)50例(A组)与CRP正常(＜10mg／L)50例对照(B组),B组匹配A组在年龄、性别和疾病种类,两组均进行体外循环心脏手术。结果A组脓毒性并发症(20％)比对照组(2％)多(P＜0.01)。这些病人微生物学阳性仅10％。A组中需要儿茶酚胺支持的占28％,而B组仅12％(P＜0.05)。A组较B组术后需呼吸机支持的时间明显延长(25.2±6.2h比6.6±0.5h)(P＜0.01)、ICU滞留时间也较B组长(4.6±0.8d比2.6±0.3d)(P＜0.05)。结论术前孤立性CRP升高的病人,体外循环术后,发生脓毒性并发症的可能性明显增加。且大多数病例微生物学实验阴性,推测大多数脓毒性并发症是由于全身炎症反应综合征的原因。