Urinary Claudin-2 Measurements as a Predictor of Necrotizing Enterocolitis: A Pilot Study

Urinary Claudin-2 Measurements as a Predictor of Necrotizing Enterocolitis: A Pilot Study
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尿液 Claudin-2 测量作为坏死性小肠结肠炎的预测因子:一项初步研究

DOI:
10.21699/jns.v4i4.282
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发表时间:
2015
影响因子:
--
通讯作者:
Catherine J Hunter M.D.
Catherine J Hunter M.D.
中科院分区:
--
文献类型:
--
作者:
Brian P Blackwood M.D.;Douglas R Wood B.S.;Carrie Y Yuan B.S.;Joseph D Nicolas;Anne Griffiths M.D.;Karen Mestan M.D.;Catherine J Hunter M.D.

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背景:坏死性小肠结肠炎(NEC)影响5-10%的新生儿重症监护室患者,最初患者可能只有非特异性临床表现。一种非侵入性的检测工具将有助于诊断。尿密蛋白的增加与成人炎症性肠病有关。方法:获得机构审查委员会批准。从患有和未患有NEC的患者中获得新生儿肠道组织样本。对肠组织进行紧密连接蛋白-2的免疫荧光分析。从6名NICU患者中收集了32份尿液样本。提取蛋白质,并使用蛋白质印迹分析测量尿密蛋白-2表达。将所有样品浓度标准化为尿肌酐。用ANOVA或学生T检验分析差异。结果与患者的临床状态相关。结果如下:新生儿肠免疫荧光分析显示,密蛋白-2存在于健康肠上皮中,并且在NEC肠组织中减少(p=0.0001)。在评价的6名患者中,3名患者患有NEC。所有3名NEC患者的尿紧密连接蛋白-2水平均出现峰值(分别为p<0.001、p<0.001、p <0.0598)。峰值似乎与新生儿败血症的其他病因、药物使用或机械通气的需要无关。活动性NEC期间的水平几乎是无NEC期间的两倍(p<0.0001)。结论:早期发现的工具将有助于早期干预和潜在的预防严重NEC。初步研究结果表明,尿密蛋白-2可能是NEC的潜在生物标志物,值得进一步研究。
Background: Necrotizing Enterocolitis (NEC) affects 5-10% of NICU patients where initially patients may have only nonspecific clinical findings. A noninvasive tool for detection would aid in diagnosis. Increased urinary claudins have been associated with active adult inflammatory bowel disease. Methods: Institutional Review Board approval was obtained. Neonatal intestinal tissue samples were obtained from patients with and without NEC. Immunofluorescence analysis of claudin-2 was performed on the intestinal tissue. Thirty two urine samples were collected from 6 NICU patients. Proteins were extracted and urinary claudin-2 expression was measured using Western Blot Analysis. All sample concentrations were normalized to urinary creatinine. Differences were analyzed with ANOVA or Student’s T-test. Findings were correlated to the patient’s clinical status. Results: Neonatal intestinal immunofluorescence analysis revealed that claudin-2 is present in healthy intestinal epithelium and is decreased in NEC intestinal tissue (p=0.0001). Of the six patients evaluated, three patients had NEC. All 3 patients with NEC had spikes in urinary claudin-2 levels (p<0.001, p<0.001, p 0.0598 respectively). Spikes did not appear to correlate with other etiologies of neonatal sepsis, medication use or need for mechanical ventilation. Levels during active NEC were almost twice that of NEC-free periods (p<0.0001). Conclusion: A tool for early detection would facilitate early intervention and potential prevention of severe NEC. Preliminary findings indicate that urinary claudin-2 may represent a potential biomarker for NEC worth further investigation.
DOI: 10.1152/ajpgi.2000.279.2.g250
发表时间: 2000-08-01
影响因子: 4.5
作者:
Mitic, LL;van Itallie, CM;Anderson, JM
通讯作者: Anderson, JM
DOI: 10.1016/j.ajpath.2013.01.013
发表时间: 2013-05-01
影响因子: 6
作者:
Bergmann, Kelly R.;Liu, Shirley X. L.;De Plaen, Isabelle G.
通讯作者: De Plaen, Isabelle G.