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1.

Background

Resistin is an immunometabolic mediator that is elevated in several inflammatory disorders. A ligand for Toll-like receptor 4, resistin modulates the recruitment and activation of myeloid cells, notably neutrophils. Neutrophils are major drivers of cystic fibrosis (CF) lung disease, in part due to the release of human neutrophil elastase- and myeloperoxidase-rich primary granules, leading to tissue damage. Here we assessed the relationship of resistin to CF lung disease.

Methods

Resistin levels were measured in plasma and sputum from three retrospective CF cohorts spanning a wide range of disease. We also assessed the ability of neutrophils to secrete resistin upon activation in vitro. Finally, we constructed a multivariate model assessing the relationship between resistin levels and lung function.

Results

Plasma resistin levels were only marginally higher in CF than in healthy control subjects. By contrast, sputum resistin levels were very high in CF, reaching 50–100 fold higher levels than in plasma. Among CF patients, higher plasma resistin levels were associated with allergic bronchopulmonary aspergillosis, and higher sputum resistin levels were associated with CF-related diabetes. Mechanistically, in vitro release of neutrophil primary granules was concomitant with resistin secretion. Overall, sputum resistin levels were negatively correlated with CF lung function, independently of other variables (age, sex, and genotype).

Conclusions

Our data establish relationships between resistin levels in the plasma and sputum of CF patients that correlate with disease status, and identify resistin as a novel mechanistic link between neutrophilic inflammation and lung disease in CF.  相似文献   
2.
同步记录72例拟诊冠心病患者头胸导联(HC)及常规导联(wilson)心电图(ECG),并与冠脉造影结果对照。结果:HC与Wilson导联ECG对冠心病诊断的敏感性分别为88.9%与81.5%,特异性33.3%与27.8%,准确性75%与68.1%;二组导联对比无明显差异(P>0.05);对右心室梗塞、缺血及左心室后壁缺血.HC导联的敏感性(91.7%)及准确性(94.4%)均显著高于Wilson导联(12.5%、70.8%,P<0.01),并与冠状动脉病变程度呈高度正相关。HC导联优于Wilson导联。  相似文献   
3.
目的 观察白术桃花汤治疗习惯性便秘的疗效。方法 自拟白术桃花汤 (白术 30g ,桃花 12g ,生地黄 30g ,枳实 10g) ,每日服 1剂 ,7d为 1个疗程。对照组服用果导片作对比观察。结果 白术桃花汤治疗习惯性便秘 117例 ,治愈 10 6例 ,好转 4例 ,总有效率 94 .0 2 %;果导片治疗 6 6例 ,治愈18例 ,好转 30例 ,总有效率 72 .73%。两组总有效率比较 ,经统计学处理P <0 0 1,差异有非常显著性意义。结论 白术桃花汤功能为补气除湿 ,增液行气 ,通调大便 ,治疗习惯性便秘疗效满意。  相似文献   
4.
目的探讨瞬时受体电位香草素受体4型通道蛋白(TRPV4)抑制剂HC067047对小鼠膝骨关节炎软骨组织的影响。 方法将30只小鼠均分为假手术组、模型组、HC067047组。假手术组仅切开右侧膝关节髌韧带内侧皮肤,不予处理膝关节囊内结构;模型组、HC067047组手术切除小鼠板股韧带及内侧半月板前角以构建膝骨关节炎,分别用生理盐水、HC067047每天10 mg/kg灌胃。qRT-PCR检测各组小鼠软骨组织中TRPV4 mRNA表达水平。番红固绿染色评估关节软骨受损程度,HE染色分析膝关节软骨下骨的骨量变化。Western blotting检测各组软骨组织中细胞焦亡标志蛋白TRPV4、Caspase-1、核苷酸结合寡聚化结构域样受体家族热蛋白结构域蛋白3(NLRP3)、凋亡相关斑点样蛋白(ASC)、GSDMD-N蛋白水平;ELISA、Western blotting分别检测血清、软骨组织中炎症因子水平。 结果与假手术组比较,模型组TRPV4、NLRP3、ASC、Caspase-1、GSDMD-N、IL-1β、IL-18水平显著升高(P<0.05)。与模型组比较,HC067047组NLRP3、ASC、Caspase-1、GSDMD-N、IL-1β、IL-18水平显著降低(P<0.05)。HC067047能明显改善关节软骨形态及降低骨关节炎受损程度,并能维持软骨下骨的骨量。 结论TRPV4抑制剂HC067047能抑制软骨组织细胞焦亡,改善膝骨关节炎小鼠关节软骨的退变。  相似文献   
5.
Interactions between rabbit-γ-immunoglobulins and model membranes (lipid monalayers, planar lipid bilayers, liposomes) have been investigated. No significant interaction was observed with immunoglobulins. However, immunoglobulins dialysed first vs aqueous buffer having pH 2 or 3 and then dialysed against pH 7 buffer presumably adopt a new conformation which allows their bindings to model membranes. This binding is hydrophobic and the immunoglobulin region interacting with the lipid acyl chains is probably located in the heavy chain, as suggested by labelling in this region by a photosensitive probe previously incorporated into the lipid hydrophobic core. Cleavage at the hinge region by papain or pepsin, or heating above 38°C, induces the loss of the hydrophobic conformation responsible for hydrophobic bindings. The binding capacity of immunoglobulins heated above 38°C is restored after momentary dialysis at pH 2. The possible existence of two Ig isomers is discussed in relation to the mechanism of γ-immunoglobulin passage through the endoplasmic membrane and fixation into the plasma membrane.  相似文献   
6.
The molecular nature of the membrane antigen that is acquired from FCS-containing media by human lymphoblastoid cells has been investigated. The presence of bovine α2, macroglobulin on the surface of Namalva cells was demonstrated by radioimmunoassay using specific antisera. Alternatively, cell-bound bovine α2,M could be detected by the more sensitive heterophile rosette assay described previously. Namalva cells grown in NHS-containing media acquired bovine α2 M upon subsequent incubation with the purified protein in a dose- and time-dependent way. Acquisition of α2 M was demonstrated using both viable and formaldehyde-fixed cells. Purified fetuin, which carries a heterophile epitope shared with bovine α2 M as well as with other glycoproteins, failed to bind with the membrane of Namalva cells. The possible role of acquired α2 macroglobulin on cells has been discussed.  相似文献   
7.
目的探讨头胸(HC)导联右胸心电图在右心病变化的临床应用价值.方法对200例17~20岁体育院校健康学生的HC导联与常规导联右胸心电图检测结果进行比较分析研究.结果HC导联的P、QRS、T波振幅均明显大于常规导联,且HC导联的QRS形态在右胸多呈正向,有R波逐渐递增,S波逐渐递减的规律,T波多数正向高尖,而常规导联的QRS的形态多数为负向,且振幅小,ST段等电位人数多,且抬高的比下移的多.结论 HC导联在反映在右室的电位变化方向优于常规导联.T波高尖的占40%,反映了体育院校的学生的生理性心肌肥厚,是心室复极的表现.  相似文献   
8.
OBJECTIVES

We tested to find out whether pravastatin restores the infarct size (IS)-limiting effect of ischemic preconditioning (IP) and if it has any effect on the IP-induced activation of adenosine producing enzyme ecto-5′-nucleotidase which plays a key role in the IP-induced cardioprotection.

BACKGROUND

The IS-limiting effect of IP is blunted by hypercholesterolemia. Recently, HMG-CoA reductase inhibitors are shown to have direct cytoprotective effects.

METHODS

Rabbits were fed with a normal or cholesterol (1%) added diet with or without pravastatin (5 mg/kg/day) treatment. Infarct size was measured after 30 min occlusion and 3 h reperfusion of circumflex coronary artery with or without the IP procedure (5 min occlusion and 10 min reperfusion). Additionally, ecto-5′-nucleotidase activities of ischemic and nonischemic myocardium were measured immediately after IP procedure.

RESULTS

This dose of pravastatin did not normalize the increased level of serum cholesterol. The IS-limiting effect of preceding IP (IS reduced from 36.7% to 9.6%, p < 0.001) was abolished by hypercholesterolemia (from 46.1% to 31.3%, p = NS) and restored by pravastatin treatment (from 35.2% to 9.4%, p < 0.001). Pravastatin treatment did not affect IS or the effect of IP under normocholesterolemia. The activation of ecto-5′-nucleotidase presented as the activity ratio of ischemic to nonischemic myocardium (3.1-fold in normocholesterolemia) was blunted by hypercholesterolemia (1.8-fold, p < 0.05) and restored by pravastatin treatment (2.9-fold).

CONCLUSIONS

Pravastatin, at the dose serum cholesterol was not normalized, restored the IS-limiting effect of IP and IP-induced ecto-5′-nucleotidase activation, which were both blunted by hypercholesterolemia. The activation of ecto-5′-nucleotidase may be worth further investigation as a possible mechanism for the hypercholesterolemia-induced retardation and pravastatin-mediated restoration of the cardioprotective effect of IP.  相似文献   

9.
Functional bowel disorders (FBDs) are the most common gastrointestinal (GI) disorders seen by gastroenterologists and primary care physicians. The disorders affect patients functioning and quality of life (QOL) and are associated with significant healthcare burden. The current theory regarding the development of FBDs suggests brain-gut axis dysfunctions associated abnormal GI motility and sensation. Recent data suggest that alterations in the intestinal microbiota may have a role in the pathogenesis of FBDs; or at least have the potential to affect intestinal functions that are thought to be relevant to the development of functional GI symptoms. This has led to growing interest of healthcare providers and patients in targeting the intestinal microbiota for the treatment of FBDs. In this article we discuss the potential role probiotic interventions in the treatment of FBDs. We review the evidence from pre-clinical and clinical studies and discuss the current recommendations for the use of probiotics for FBDs in clinical practice.  相似文献   
10.
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