BACKGROUND:Harmane (1-methyl-9H-pyrido[3,4-b]indole), a neurotoxin, may be an environmental risk factor for essential tremor (ET). Harmane and related chemicals are toxic to the cerebellum. Whether it is through this mechanism (cerebellar toxicity) that harmane leads to ET is unknown. Impaired olfaction may be a feature of cerebellar disease. OBJECTIVE:To determine whether blood harmane concentrations correlate with olfactory test scores in patients with ET. METHODS:Blood harmane concentrations were quantified using high performance liquid chromatography. Odor identification testing was performed with the University of Pennsylvania Smell Identification Test (UPSIT). RESULTS:In 83 ET cases, higher log blood harmane concentration was correlated with lower UPSIT score (rho=-0.46, p<0.001). 25/40 (62.5%) cases with high log blood harmane concentration (based on a median split) had low UPSIT scores (based on a median split) vs. 12/43 (27.9%) ET cases with low log blood harmane concentration (adjusted odd ratios (OR) 4.04, 95% confidence intervals (CI) 1.42-11.50, p=0.009). When compared with the low log blood harmane tertile, the odds of olfactory dysfunction were 2.64 times higher in cases in the middle tertile and 10.95 times higher in cases in the high tertile. In 69 control subjects, higher log blood harmane concentration was not correlated with lower UPSIT score (rho=0.12, p=0.32). CONCLUSIONS:Blood harmane concentrations were correlated with UPSIT scores in ET cases but not controls. These analyses set the stage for postmortem studies to further explore the role of harmane as a cerebellar toxin in ET.

译文

背景:Harmane(1-甲基-9H-吡啶并[3,4-b]吲哚)是一种神经毒素,可能是原发性震颤(ET)的环境危险因素。 Harmane和相关化学物质对小脑有毒。烷烃是否通过这种机制(小脑毒性)导致ET尚不清楚。嗅觉障碍可能是小脑疾病的特征。
目的:确定ET患者血液中的烷烃含量是否与嗅觉测试成绩相关。
方法:采用高效液相色谱法定量测定甲醛的血中烷烃浓度。气味识别测试是通过宾夕法尼亚大学气味识别测试(UPSIT)进行的。
结果:在83例ET患者中,较高的对数血液harmane浓度与较低的UPSIT评分相关(rho = -0.46,p <0.001)。 25/40(62.5%)的高对数血液harmane浓度(基于中位数拆分)病例的UPSIT得分较低(基于中位数的分裂),而12/43(27.9%)的ET血液血液harmane浓度较低的病例(27.9%)调整后的奇数比(OR)4.04,95%置信区间(CI)1.42-11.50,p = 0.009)。与低对数血液harmane三分位数相比,中三分位数的患者嗅觉功能障碍的几率高2.64倍,高三分位数的患者嗅觉功能障碍的几率高10.95倍。在69名对照受试者中,较高的log血液harmane浓度与较低的UPSIT得分无关(rho = 0.12,p = 0.32)。
结论:ET病例的血液中甲醛含量与UPSIT评分相关,而与对照组无关。这些分析为进行死后研究奠定了基础,以进一步探讨harmane作为ET中小脑毒素的作用。

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