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[求助]
求翻译一篇摘要，谢谢
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Longterm safety and efficacy data generated in Europe from usage of fumaric acid formulations in the latter disease constituted grounds to investigate their effects in MS patients. Dimethyl fumarate (DMF) was found to be the active principle in those formulations and in vitro studies have demonstrated that DMF has immune-modulatory properties exerted through abilities to divert cytokine production toward a Th2 profile, both on lymphocytes and microglial cells. More importantly, DMF was discovered to impact the anti-oxidative stress cell machinery promoting the transcription of genes downstream to the activation of the nuclear factor (erythroid derived 2)-like2 (NRF2). DMF exposure increases the cytosol concentrations of NRF2, which besides immune regulatory effects, has the potential for cytoprotection on glial cells, oligodendrocytes and neurons. Extensive and rigorous clinical trials have assessed the efficacy and safety of DMF at the dose of 240 mg twice and three times a day in relapsingremitting MS patients during one phase IIb and two phase III trials. Robust, positive results were obtained across a number of clinical and paraclinical parameters. In one study (DEFINE), the relative reductions of the adjusted annualized relapse rate of the low and high dose regimens in comparison with placebo were 53% and 48%, respectively (p < 0.001 for both comparisons). In the other trial (CONFIRM), DMF decreased the annualized relapse rate in comparison with placebo by 44% in the lower and by 51% in higher dosage group (also p < 0.001). The number and size of lesions as detected by magnetic resonance imaging were also significantly decreased in comparison with the patients receiving DMF at every dosage. Multiple post hoc and subgroup analyses corroborated the clinical data, rendering DMF an appealing medication whose potential for impacting the degenerative aspects of MS remains to be explored. |
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baoshanqiu
至尊木虫 (著名写手)
- 翻译EPI: 204
- 应助: 103 (高中生)
- 金币: 15293.5
- 红花: 41
- 帖子: 1611
- 在线: 431.6小时
- 虫号: 3856202
- 注册: 2015-05-08
- 性别: GG
- 专业: 胃肠道免疫相关疾病
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小丸丸9: 金币+50, 翻译EPI+1, 虽然翻译得不怎么好，不过辛苦了。谢谢 2015-06-04 10:15:46
小丸丸9: 金币+50, 翻译EPI+1, 虽然翻译得不怎么好，不过辛苦了。谢谢 2015-06-04 10:15:46
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长期 欧洲使用延胡索酸配方治疗晚期疾病得到的安全和有效性的资料成为研究该类配方对多发性硬化症疗效的基础。二甲基延胡索酸（DMF)是该类配方的主要活性成分。体外使用表明，DMF 具有免疫调节特性，表现为能歧化淋巴细胞和小胶质细胞的细胞因子产生朝Th2方向。更重要的是DMF能动员抗氧化应激细胞机制提高激活核因子（红细胞样衍化因子2）（NRF2)下游基因转录活性。胶质细胞、少突细胞和神经元暴露于DMF后，细胞质NRF2浓度升高。这不仅具有免疫调节作用，还具有保护细胞的潜能。广泛而严格的临床试验已证实了DMF 的疗效和安全性。在一个IIb和两个III期临床试验中DMF在240mg，每天2次和3次的剂量可延迟多发性硬化症病人的复发。在许多临床和亚临床参数中得到稳定的阳性结果。在一项研究（确定）中，低剂量和高剂量组与安慰剂组比较，调整的年复发率相对减少，分别为53%和48% （二者比较均p<0.001).在另一个临床试验（确认）中，DMF组与安慰剂组比较减少年复发率在低剂量为44%，高剂量为51%（也是p<0.001)。在每一个剂量下接受DMF的病人经核磁共振成像检测损伤的数量和大小都显著降低。多次随访和子群分析确证了临床资料，使DMF成为有希望的治疗药物。它对多发性硬化症变性方面的影响有待进一步探索。 |
2楼2015-06-04 00:20:38
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