Opposite effects of substance P and calcitonin gene-related peptide in oxazolone colitis

Background

Extrinsic sensory neurons play a crucial role in aberrant immune responses in colitis. The activation of peptidergic sensory nerve fibres is accompanied by a release of the neuropeptides calcitonin gene-related peptide (CGRP) and substance P (SP). SP levels increase whilst CGRP levels decrease in colon specimens from patients with inflammatory bowel disease; thus suggesting the pro- and anti-inflammatory roles, respectively, of these neuropeptides.

Methods

Oxazolone (4-ethoxymethylene-2-phenyl-2-oxazolin-5-one) colitis was induced in wild-type (WT), SP and CGRP knockout (^−/−) mice. CGRP^−/− mice were treated with the neurokinin 1-receptor antagonist CP-96345 (CP). The permeability of the mouse colon was evaluated by Evans Blue uptake. Cytokines produced by colonic lamina propria mononuclear cells were measured by ELISA.

Results

Colons of WT, CGRP^−/− and SP^−/− mice showed similar tissue architecture and permeability. SP^−/− mice were protected against oxazolone colitis, whereas CGRP^−/− showed increased susceptibility to colitis compared to WT mice. SP^−/− and CP-treated CGRP^−/− mice showed no significant body weight loss during the period of sickness in contrast to untreated CGRP^−/− and WT mice. Decreased production of IL-4, IL-5, and IL-13 by colonic lamina propria mononuclear cells of the protected SP^−/− mice confirms the crucial role of these cytokines in oxazolone colitis.

Conclusion

We demonstrate that the neuropeptides CGRP and SP exert opposing effects in oxazolone colitis and provide further evidence for a prominent neuroimmune association in the gut.     

维生素D缺乏与干眼关系的研究进展

干眼是泪液和眼球表面的多因素疾病,能引起不适、视觉障碍和泪膜不稳定,可能损害眼表,伴有泪液渗透压升高和眼表炎症。维生素D是一种脂溶性维生素,在皮肤中产生或随食物摄取,具有多种功能,对骨骼、肠道、肾脏,特别是免疫系统等有重要的调节作用。近年研究发现,维生素D缺乏与干眼存在密切联系。本文就维生素D缺乏与干眼之间的关系进行综述。     

Previous immunosuppressive therapy is a risk factor for immune reconstitution inflammatory syndrome in Whipple's disease

Introduction

Whipple's disease is a rare chronic infection caused by Tropheryma whipplei. Although most patients respond to antibiotics, in some of them the start of the treatment is followed by recurrence of inflammation. Since polymerase chain reaction is negative for Tropheryma whipplei, this reinflammation cannot be a relapse of Whipple's disease itself. Very recently, it has been recognised as a complication of Whipple's disease and defined immune reconstitution inflammatory syndrome (IRIS). Our aim is to study the prevalence and the clinical features of IRIS in Italian patients with Whipple's disease.

Methods

Evidence of IRIS was retrospectively revaluated in the clinical notes of 22 patients with Whipple's disease. Patients with no evidence of IRIS served as controls for the clinical findings.

Results

Recurrence of arthralgia and/or fever allowed a diagnosis of IRIS in 5/22 patients. One patient died. Previous immunosuppressive therapy was found in all patients with IRIS but only in 7/17 controls (Fisher test, p = 0.039). Age at diagnosis and diagnostic delay were higher in patients with IRIS compared to controls. However, statistical significance was not reached.

Conclusions

IRIS is a frequent complication of Whipple's disease and it can be fatal. The risk of IRIS is greatly increased in patients previously treated with immunosuppressive therapy.     

小梁网细胞氧化应激在青光眼发病中的研究进展

青光眼是一种常见的不可逆性致盲眼病,病理性眼压升高为主要临床特征。眼压的形成与房水循环密切相关,房水动力学异常,会引起病理性眼压升高。小梁网是房水外流通道的主要组成部分,对维持正常眼压起到非常关键的作用。氧化应激是导致青光眼眼压升高的直接危险因素,表现为氧化与抗氧化作用的失衡。小梁网细胞氧化应激可能导致细胞外基质的沉积与退行性变,使细胞发生自噬和衰老,造成小梁网细胞功能障碍,最终导致房水外流阻力增大,引起病理性眼压升高。本文将针对小梁网细胞氧化应激与青光眼关系的研究进展进行综述,以期为进一步的临床研究提供依据,为探讨青光眼的发病机制、预防及治疗青光眼提供参考。     

复方牛胎肝提取物联合阿德福韦酯治疗慢性乙型肝炎疗效观察

目的观察复方牛胎肝提取物片联合阿德福韦酯片治疗慢性乙型肝炎患者对肝纤维化的临床疗效。方法将42例慢性乙型肝炎患者随机分为治疗组21例,给予口服复方牛胎肝提取物片及阿德福韦酯片和对照组21例,给予口服阿德福韦酯片,疗程均为48周。观察两组患者在治疗前及治疗48周后两次肝穿刺活检病理学变化和血清透明质酸（HA）的变化。结果治疗后治疗组肝组织炎症活动度2例加重,10例无明显变化,9例减轻,对照组肝组织炎症活动度6例加重,12例无明显变化,3例减轻。治疗组肝脏炎症活动度改善优于对照组,差异有显著性（P=0.029）;治疗组纤维化程度2例加重,10例无明显变化,9例减轻,对照组纤维化程度9例加重,9例无明显变化,3例减轻。治疗组纤维化程度改善明显优于对照组,差异有显著性（P=0.006）;治疗组治疗后HA下降明显（P〈0.001）,对照组未见降低,两组间差异有显著性（P〈0.001）。结论复方牛胎肝提取物片联合阿德福韦酯片能显著地改善肝脏炎症活动度和纤维化程度,优于单用阿德福韦酯治疗。     

系统性炎症与慢性阻塞性肺疾病大动脉弹性的相关性研究

目的 探讨慢性阻塞性肺疾病( COPD)患者系统性炎症与大动脉弹性之间的关系.方法 采用病例对照研究的方法,研究对象分为两组:病例组:102例COPD稳定期患者;对照组:83例同期健康体检者.两组研究对象用同样的方法应用脉搏波速度自动测定仪测定颈-股动脉搏波传导速度(C-FPWV)和颈-足背动脉搏波传导速度(C-DPWV)作为大动脉弹性的参数,应用免疫比浊法测定血清超敏C反应蛋白(hs-CRP)浓度,放射免疫分析法测定血清白介素1(IL-1)、白介素6(IL-6)、肿瘤坏死因子α(TNF-α)浓度,这些炎性因子的测定作为系统性炎症的参数,与正常对照组作比较.结果 ①病例组C-FPWV、C-DPWV、IL-1、IL-6、TNF-α、hs-CRP均高于正常对照组,差异有统计学意义,P＜0.05.②病例组C-FPWV与年龄、吸烟指数、收缩压、IL-1、IL-6、TNF-α、hs-CRP呈正相关,P＜0.05.C-DPWV与年龄、吸烟指数、IL-1、IL-6、TNF-α、hs-CRP呈正相关,P＜0.05.③IL-6、吸烟指数、TNF-α是影响C-FPWV的独立因素;IL-6是影响GDPWV的独立因素.结论 系统性炎症与COPD患者大动脉弹性间存在相关性.系统性炎症可能参与了COPD患者大动脉弹性下降的发病过程,它是COPD患者发生心血管疾病的高危因素.     

白血病抑制因子与支气管哮喘

在支气管哮喘(简称哮喘)的发病过程中,机体神经、免疫与内分泌系统均参与其中,它是一个多步骤的过程,涉及到大量的细胞因子、炎症介质和神经递质.白血病抑制因子(leukemia inhibitory factor,LIF)是连接神经-免疫-内分泌系统网络的桥梁,LIF通过调节多种炎症细胞,如嗜酸粒细胞、淋巴细胞和肥大细胞等,促进炎性介质的释放;促进气道感觉神经末梢释放P物质等神经肽,上调气道上皮细胞神经激肽-1受体(neurokinin-1 receptor,NK-1R)的表达,诱发气道神经源性炎症;此外,LIF还可下调糖皮质激素受体的表达,导致糖皮质激素抵抗.因此LIF水平在哮喘患者血清、痰液、支气管肺泡灌洗液、支气管黏膜中均可有所升高.本文就LIF的生物学特征以及与哮喘发病的关系作一综述,旨在为探讨哮喘的发病机制和临床治疗提供理论依据.     

Nitric oxide boosts TLR‐4 mediated lipocalin 2 expression in chondrocytes

Lipocalin 2 (LCN2) has recently emerged as a novel adipokine involved in different processes including arthritis and chondrocyte inflammatory response. However, little is known about its activity on chondrocyte homeostasis and its regulation by nitric oxide (NO) Hence, we performed a set of experiments aimed to achieve a better understanding of this relationship. Cell vitality was tested in the ATDC5 cell line by the MTT colorimetric assay. Protein expression and gene expression was evaluated by Western blot and real time RT‐PCR, respectively. NO production (determined as nitrite accumulation) was assayed by the Griess reaction. First, we demonstrated that LCN2 decreased murine chondrocytes vitality. Next, LCN2 co‐stimulation with LPS enhanced NOS2 protein expression by murine chondrocytes. In addition, inhibition of LPS‐induced nitric oxide production by aminoguanidine, a selective NOS2 inhibitor, significantly reduced LPS‐mediated LCN2 expression. In contrast, treatment of murine chondrocytes with sodium nitroprussiate (SNP), a classic NO donor, scarcely induced LCN2 expression. Intriguingly, SNP addition to LPS‐challenged chondrocytes, treated with aminoguanidine, provoked a strong induction of LCN2 expression. Finally, murine ATDC5 cells, co‐cultured with LPS pre‐challenged macrophages, had higher LCN2 expression in comparison with murine chondrocytes co‐cultured with non pre‐challenged macrophages. In this work we have described for the first time that NO is able to exert a control on LCN2 expression, suggesting the existence of a feedback loop regulating its expression. © 2013 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 31:1046–1052, 2013     

The Relationship between the MEFV Genotype,Clinical Features,and Cytokine-Inflammatory Activities in Patients with Familial Mediterranean Fever

Familial Mediterranean Fever (FMF) is an autosomal recessive disease characterized by periodic attacks of fever and polyserositis. The effects of the MEFV genotype differences on clinical picture and inflammatory activity have not been well documented. The aim of this study was to investigate levels of conventional inflammation markers, procalcitonin, interleukin levels, TNF-alpha, and C5a levels in patients with FMF who had different MEFV genotypes and compare them with those of healthy subjects. The study consisted of 41 patients with FMF (F/M: 23/18), and 31 healthy subjects (F/M: 18/13). Tests were performed during the attack-free period.

White-blood cell count, CRP and IL-8 levels were higher in patients with FMF than in healthy subjects (p < 0.05) and also higher in M680I carriers than in the patients with M694V allele carriers. However, ESR, fibrinogen, procalcitonin, IL-6, C5a, TNF-alpha, and IgD levels were not significantly different between patients and healthy subjects (p > 0.05). Arthralgia or arthritis was significantly higher in M694V carriers than in non-M694V carriers (p < 0.05). It is concluded that the clinical features and inflammatory-cytokine activities were higher in patients with FMF during the attack-free period than in healthy subjects, and the different genotype might be related to different clinical pictures.     

Hypertension,fluid overload and micro inflammation are associated with left ventricular hypertrophy in maintenance hemodialysis patients

Abstract

This cross-sectional study aims to identify the potential risk factors of left ventricular hypertrophy (LVH) in hemodialysis (HD) patients. Echocardiography, anthropometric measurements and biochemical analyses were performed for 112 HD patients. In univariate analysis, body mass index, systolic blood pressure, diastolic blood pressure, glycosylated hemoglobin, glycated albumin, high sensitivity C-reactive protein (hs-CRP), cardiac troponin T (cTnT), amino-terminal pro-B-natriuretic peptide (NT-proBNP) and carotid artery intima-media thickness were positively correlated with left ventricular mass index (LVMI); pre-albumin, serum creatinine, left ventricular ejection fraction (LVEF) and fractional shortening were negatively correlated with LVMI. Linear regression analysis showed systolic blood pressure, NT-proBNP and LVEF were independently associated with LVMI. According to a binary logistic regression model, higher systolic blood pressure, NT-proBNP and hs-CRP levels showed independent correlation with LVH. Receiver operator characteristic curves analysis showed the associations between NT-proBNP and LVH more closely than hs-CRP and cTnT. The area under the curve for NT-proBNP, hs-CRP and cTnT was 0.762 (95% CI: 0.660–0.864, p?<?0.001), 0.734 (95% CI: 0.624–0.844, p?<?0.001) and 0.677 (95% CI: 0.563–0.790, p?=?0.004), respectively. These data support the main conclusions: hypertension, fluid overload and micro inflammation are associated with LVH in maintenance HD patients. It demonstrates traditional and nontraditional risk factors all play important roles in the development of LVH.