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一氧化氮作为多发性硬化症的活性标志物。

Nitric oxide as an activity marker in multiple sclerosis.

作者信息

Acar G, Idiman F, Idiman E, Kirkali G, Cakmakçi H, Ozakbaş S

机构信息

Department of Neurology, Dokuz Eylül University, School of Medicine, Izmir, Turkey.

出版信息

J Neurol. 2003 May;250(5):588-92. doi: 10.1007/s00415-003-1041-0.

Abstract

Nitric oxide (NO) molecules have one of the most important roles in the pathogenesis of multiple sclerosis (MS). It has been stated that a continuous and high concentration of NO metabolites in CSF and in the serum of MS patients in relapse may cause toxic damage to myelin and oligodendroglia. The aim of this study was to investigate whether NO is a marker of disease activity and is correlated with other disease activity markers such as active lesions on brain magnetic resonance imaging (MRI) and increased immunoglobulin G (IgG) index. Cerebrospinal fluid (CSF) and peripheral serum (PS) samples were taken from patients with definite MS (n = 24) during relapse and remission and from control subjects (n = 18). The Griess reaction was used to measure the NO metabolites, nitrite and nitrate in CSF and PS. Cranial MRI was carried out with triple dose (0,3 mmol/kg) gadolinium and the IgG index was determined. Nitrite and nitrate concentrations (NNCs) of CSF were 11.16 +/- 8.60 micromol/ml in relapse and 6.72 +/- 3.50 micromol/ml in remission, whereas in PS they were 12.89 +/- 7.62 micromol/ml during relapse and 12.35 +/- 6.62 micromol/ml during remission. In control subjects NNCs in CSF and PS were 7.42 +/- 2.81 micromol/ml and 4.37 +/- 1.63 micromol/ml respectively. NNCs in CSF during relapse period were significantly higher than those of both remission phase and control subjects (p = 0.000). Although serum NNCs did not differ in relapse and remission, they were still higher than normal controls. Validity analysis revealed that NNC measurement in CSF was 71 % specific and 66 % sensitive to disease activity. The most important result was the significant correlation of increased NNCs with the existence of active lesion in cranial MRI and an increase in IgG index (p < 0.05).In conclusion, these results add background data to assist in further outlining the possible role of NO in the pathogenesis of MS. Together with the other markers it may be used as an activity marker in relapses of MS.

摘要

一氧化氮(NO)分子在多发性硬化症(MS)的发病机制中起着最重要的作用之一。据报道,复发期MS患者脑脊液和血清中持续高浓度的NO代谢产物可能会对髓鞘和少突胶质细胞造成毒性损伤。本研究的目的是调查NO是否为疾病活动的标志物,以及它是否与其他疾病活动标志物相关,如脑磁共振成像(MRI)上的活动性病变和免疫球蛋白G(IgG)指数升高。在复发期和缓解期从确诊为MS的患者(n = 24)以及对照受试者(n = 18)中采集脑脊液(CSF)和外周血清(PS)样本。采用格里斯反应测量CSF和PS中的NO代谢产物亚硝酸盐和硝酸盐。使用三倍剂量(0.3 mmol/kg)钆进行头颅MRI检查,并测定IgG指数。CSF中的亚硝酸盐和硝酸盐浓度(NNCs)在复发期为11.16±8.60 μmol/ml,缓解期为6.72±3.50 μmol/ml,而PS中的NNCs在复发期为12.89±7.62 μmol/ml,缓解期为12.35±6.62 μmol/ml。对照受试者CSF和PS中的NNCs分别为7.42±2.81 μmol/ml和4.37±1.63 μmol/ml。复发期CSF中的NNCs显著高于缓解期和对照受试者(p = 0.000)。虽然血清NNCs在复发期和缓解期没有差异,但仍高于正常对照组。有效性分析显示,CSF中NNC测量对疾病活动的特异性为71%,敏感性为66%。最重要的结果是NNCs升高与头颅MRI上活动性病变的存在以及IgG指数升高显著相关(p < 0.05)。总之,这些结果为进一步阐明NO在MS发病机制中的可能作用提供了背景数据。与其他标志物一起,它可作为MS复发时的活动标志物。

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