Degenerative neurological and neuromuscular disease最新文献

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Effect of the micro-immunotherapy medicine 2LPARK® on rat primary dopaminergic neurons after 6-OHDA injury: oxidative stress and survival evaluation in an in vitro model of Parkinson’s disease 微免疫疗法药物2LPARK®对6-OHDA损伤后大鼠原代多巴胺能神经元的影响：帕金森病体外模型中的氧化应激和存活评估

Q3 CLINICAL NEUROLOGY

Degenerative neurological and neuromuscular disease

Pub Date : 2019-07-08 DOI: 10.2147/DNND.S202966

N. L. Lilli, Delphine Révy, S. Robelet, B. Lejeune

Background Parkinson’s disease (PD) is a neurodegenerative disease characterized by motor impairments and resulting from progressive degenerative loss of midbrain dopaminergic (DAergic) neurons in the substantia nigra. Although the main cause of the loss of DAergic neurons is still unknown, various etiopathogenic mechanisms are distinguished, including release and accumulation of endogenous excitotoxic mediators along with the production of oxidative free radicals. Several neurotrophic and growth factors are known to increase DAergic neuronal survival and enhance antioxidant mechanisms. In this context, the micro-immunotherapy (MI) approach consists to regulate the immune system in order to protect DAergic neurons and control oxidative stress. Purpose The aim of the present study was to investigate the effect of the MI medicine (MIM), 2LPARK® (Labo’Life), on oxidative stress and on the number of neurons positive for tyrosine hydroxylase (TH), in an in vitro model of PD. Methods Rat primary mesencephalic DAergic neurons cultures were pre-treated for 1 hr with the MIM (10 μM and 10 mM), placebo (10 μM and 10 mM) or brain-derived neurotrophic factor (BDNF; 3.3 μM) and then intoxicated with 6-hydroxydopamine (6-OHDA; 20 μM) for 48 hrs. After incubation, cells were incubated 30 mins at 37°C with CellROX green reagent and number of labeled cells were quantified. Then, cells were fixed and incubated with anti-TH antibody and the number of TH+ neurons was evaluated. Results We showed that, contrary to placebo, MIM was able to reduce oxidative stress and protect DAergic neurons from 6-OHDA-induced cell death. Conclusion Our results demonstrate the in vitro efficacy of MIM on two essential mechanisms of PD and propose the MI approach as a new ally in the regulation of neuroinflammation and in the treatment of this degenerative disease.

背景帕金森病（PD）是一种以运动障碍为特征的神经退行性疾病，由黑质中脑多巴胺能神经元的进行性退行性丧失引起。尽管DA能神经元损失的主要原因尚不清楚，但各种病因机制是不同的，包括内源性兴奋性毒性介质的释放和积累以及氧化自由基的产生。已知几种神经营养和生长因子可增加DA能神经元的存活率并增强抗氧化机制。在这种情况下，微免疫疗法（MI）方法包括调节免疫系统，以保护DA能神经元并控制氧化应激。目的本研究的目的是研究MI药物2LPARK®（Labo'Life）对PD体外模型中氧化应激和酪氨酸羟化酶（TH）阳性神经元数量的影响，安慰剂（10μM和10 mM）或脑源性神经营养因子（BDNF；3.3μM），然后用6-羟基多巴胺（6-OHDA；20μM）陶醉48小时。孵育后，用CellROX绿色试剂在37°C下孵育细胞30分钟，并定量标记细胞的数量。然后，将细胞固定并与抗TH抗体孵育，并评估TH+神经元的数量。结果与安慰剂相反，MIM能够降低氧化应激，保护DA能神经元免受6-OHDA诱导的细胞死亡。结论我们的研究结果证明了MIM在PD的两个重要机制上的体外疗效，并提出MI方法作为调节神经炎症和治疗这种退行性疾病的新盟友。

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引用次数: 8

Efficacy, safety, and quality-of-life of treatments for acute relapses of multiple sclerosis: results from a literature review of randomized controlled trials 多发性硬化症急性复发治疗的疗效、安全性和生活质量：随机对照试验的文献综述结果

Q3 CLINICAL NEUROLOGY

Degenerative neurological and neuromuscular disease

Pub Date : 2019-07-01 DOI: 10.2147/DNND.S208815

J. Costello, A. Njue, M. Lyall, A. Heyes, Nancy Mahler, M. Philbin, T. Nazareth

Background Intravenous methylprednisolone (IVMP), repository corticotropin injection (RCI), plasmapheresis (PMP), and intravenous immunoglobulin (IVIG) are used in the treatment of acute multiple sclerosis (MS) relapse. A systematic literature review (SLR) of randomized controlled trials (RCTs) was conducted to examine the highest quality evidence available for these therapies. Methods English-language articles were searched in MEDLINE, Embase, and Cochrane Library through May 2016 per Preferred Reporting Items for Systematic Reviews and Meta-Analyses standards. MS conferences, SLRs, and bibliographies of included studies were also searched. Eligible studies included adults treated with ≥1 aforementioned therapy. Results Twenty-three RCTs were identified: 22 on efficacy, 11 on safety, and 3 on QOL (ie 18 IVMP, 2 RCI, 2 PMP, and 2 IVIG). IVMP and RCI improved relapse-related disability; however, IVIG and PMP showed inconsistent efficacy. QOL data were only ascertained for IVMP. Conclusions RCTs indicate IVMP and RCI are efficacious and well tolerated treatments for MS relapse. Overall, many RCTs were dated, with sample sizes of fewer than 30 patients and no definitions for relapse nor clinically significant change. Contemporary evidence generation for all relapse treatments of interest, across efficacy, safety, and QOL outcomes, is still needed.

背景静脉注射甲基强的松龙（IVMP）、促肾上腺皮质激素注射液（RCI）、血浆置换术（PMP）和静脉注射免疫球蛋白（IVIG）用于治疗急性多发性硬化症（MS）复发。对随机对照试验（RCT）进行了系统文献综述（SLR），以检查这些疗法的最高质量证据。方法根据系统评价和荟萃分析标准的首选报告项目，在MEDLINE、Embase和Cochrane图书馆检索截至2016年5月的英语文章。还检索了MS会议、SLR和纳入研究的目录。符合条件的研究包括接受≥1种上述治疗的成年人。结果共确定23项随机对照试验：疗效22项，安全性11项，生活质量3项（IVMP 18项，RCI 2项，PMP 2项，IVIG 2项）。IVMP和RCI改善了复发相关的残疾；然而，IVIG和PMP显示出不一致的疗效。仅确定IVMP的QOL数据。结论随机对照试验表明IVMP和RCI是治疗MS复发的有效且耐受性良好的治疗方法。总体而言，许多随机对照试验都是过时的，样本量不到30名患者，没有复发的定义，也没有临床显著变化。仍然需要为所有感兴趣的复发治疗提供现代证据，包括疗效、安全性和生活质量结果。

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引用次数: 11

Comorbidities in multiple sclerosis-a plea for interdisciplinary collaboration to improve the quality of life of MS patients. 多发性硬化症合并症——呼吁跨学科合作以提高MS患者的生活质量。

IF 2.1 Q3 CLINICAL NEUROLOGY

Degenerative neurological and neuromuscular disease

Pub Date : 2019-06-13 eCollection Date: 2019-01-01 DOI: 10.2147/DNND.S204555

Hans-Klaus Goischke

The negative influence of comorbidities on the quality of life of people with multiple sclerosis is evident and the problem is increasingly acknowledged by numerous international studies in long-term care. One therapeutic option would be an add-on therapy with vitamin D (VD), with the aim of achieving a therapeutically effective dose. The individually required VD dose must be tested, since the response to a certain dose is subject to variations between individuals. A possible toxicity with increased 1.25(OH)D3 (active VD metabolite) is largely prevented by increased activity of 24-hydroxylase (CYP24A1). Monitoring of serum VD levels as well as serum calcium and phosphate levels (optional Ca excretion in 24-hour urine, Ca creatinine ratio in urine) provides safety and is necessary because possible mutations on the (catabolic) CYP24A1 gene can lead to a partial or total loss of 24-hydroxylase activity and provoke hypercalcemia/hyperphosphatemia. The main therapeutic objective is to maintain functional and social independence by using drugs with a high safety profile. The prevention and optimal management of comorbidities can influence the quality of life of patients with MS (PwMS) when included in patient care. Adequate measures can reduce the burden of MS only if the risk of comorbidity is reduced through targeted monitoring, early detection and diagnosis. Such a strategy will contribute to influencing the premature mortality of patients with MS. If VD is recognized as a "multipurpose steroid hormone", it could also be used to maintain cognitive function and prevent premature possible dementia, especially as there is evidence that VD deficiency correlates with brain atrophy (hippocampus). At present, MS therapy is still a balancing act between therapeutically efficient action and the management of unexpected side effects, with VD add-on therapy being almost unproblematic and most likely to be accepted by PwMS.

合并症对多发性硬化症患者生活质量的负面影响是显而易见的，长期护理领域的许多国际研究越来越认识到这个问题。一种治疗选择是使用维生素D（VD）进行附加治疗，目的是达到治疗有效剂量。必须测试个人所需的VD剂量，因为对特定剂量的反应会因个人而异。1.25（OH）D3（活性VD代谢产物）增加的可能毒性在很大程度上通过增加24-羟化酶（CYP24A1）的活性来预防。监测血清VD水平以及血清钙和磷酸盐水平（24小时尿液中可选的钙排泄量、尿液中的钙-肌酸酐比率）提供了安全性，并且是必要的，因为（分解代谢）CYP24A1基因上可能的突变会导致24-羟化酶活性的部分或全部丧失，并引发高钙血症/高磷血症。主要治疗目标是通过使用具有高安全性的药物来保持功能和社会独立性。当纳入患者护理时，合并症的预防和最佳管理会影响多发性硬化症患者的生活质量。只有通过有针对性的监测、早期发现和诊断来降低合并症的风险，适当的措施才能减轻多发性硬化症的负担。这种策略将有助于影响多发性硬化症患者的过早死亡。如果VD被认为是一种“多用途类固醇激素”，它也可以用于维持认知功能和预防可能的过早痴呆，特别是有证据表明VD缺乏与脑萎缩（海马体）相关。目前，多发性硬化症治疗仍然是治疗有效作用和意外副作用管理之间的平衡行为，VD附加治疗几乎没有问题，最有可能被PwMS接受。

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引用次数: 0

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