N. L. Lilli, Delphine Révy, S. Robelet, B. Lejeune
{"title":"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","authors":"N. L. Lilli, Delphine Révy, S. Robelet, B. Lejeune","doi":"10.2147/DNND.S202966","DOIUrl":"https://doi.org/10.2147/DNND.S202966","url":null,"abstract":"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.","PeriodicalId":93972,"journal":{"name":"Degenerative neurological and neuromuscular disease","volume":"9 1","pages":"79 - 88"},"PeriodicalIF":0.0,"publicationDate":"2019-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/DNND.S202966","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49479214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J. Costello, A. Njue, M. Lyall, A. Heyes, Nancy Mahler, M. Philbin, T. Nazareth
{"title":"Efficacy, safety, and quality-of-life of treatments for acute relapses of multiple sclerosis: results from a literature review of randomized controlled trials","authors":"J. Costello, A. Njue, M. Lyall, A. Heyes, Nancy Mahler, M. Philbin, T. Nazareth","doi":"10.2147/DNND.S208815","DOIUrl":"https://doi.org/10.2147/DNND.S208815","url":null,"abstract":"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.","PeriodicalId":93972,"journal":{"name":"Degenerative neurological and neuromuscular disease","volume":"9 1","pages":"55 - 78"},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/DNND.S208815","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48642648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comorbidities in multiple sclerosis-a plea for interdisciplinary collaboration to improve the quality of life of MS patients.","authors":"Hans-Klaus Goischke","doi":"10.2147/DNND.S204555","DOIUrl":"10.2147/DNND.S204555","url":null,"abstract":"<p><p>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 (<i>CYP24A1</i>). 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) <i>CYP24A1</i> 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.</p>","PeriodicalId":93972,"journal":{"name":"Degenerative neurological and neuromuscular disease","volume":"9 ","pages":"39-53"},"PeriodicalIF":2.1,"publicationDate":"2019-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0c/8a/dnnd-9-39.PMC6584285.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41223823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}