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Fumarate dimethyl

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https://www.readbyqxmd.com/read/28332255/what-should-we-expect-from-multiple-sclerosis-therapy-results-of-an-integrated-analysis-of-delayed-release-dimethyl-fumarate-pivotal-trials
#1
EDITORIAL
R Lanzillo
No abstract text is available yet for this article.
March 22, 2017: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
https://www.readbyqxmd.com/read/28328179/effect-of-delayed-release-dimethyl-fumarate-on-no-evidence-of-disease-activity-in-relapsing-remitting-multiple-sclerosis-integrated-analysis-of-the-phase-iii-define-and-confirm-studies
#2
E Havrdova, G Giovannoni, R Gold, R J Fox, L Kappos, J Theodore Phillips, M Okwuokenye, J L Marantz
BACKGROUND AND PURPOSE: Significant effects on clinical/neuroradiological disease activity have been reported in patients with relapsing-remitting multiple sclerosis treated with delayed-release dimethyl fumarate (DMF) in phase III DEFINE/CONFIRM trials. We conducted a post hoc analysis of integrated data from DEFINE/CONFIRM to evaluate the effect of DMF on achieving no evidence of disease activity (NEDA) in patients with relapsing-remitting multiple sclerosis. METHODS: The analysis included patients randomized to DMF 240 mg twice daily, placebo or glatiramer acetate (CONFIRM only) for ≤2 years...
March 22, 2017: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
https://www.readbyqxmd.com/read/28300316/dimethyl-fumarate-finally-coming-of-age
#3
D M W Balak
No abstract text is available yet for this article.
March 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28283486/systematic-literature-review-and-network-meta-analysis-in-highly-active-relapsing-remitting-multiple-sclerosis-and-rapidly-evolving-severe-multiple-sclerosis
#4
Eline Huisman, Katerina Papadimitropoulou, James Jarrett, Matthew Bending, Zoe Firth, Felicity Allen, Nick Adlard
OBJECTIVE: Multiple sclerosis (MS) is a chronic, neurodegenerative autoimmune disorder affecting the central nervous system. Relapsing-remitting MS (RRMS) is the most common clinical form of MS and affects ∼85% of cases at onset. Highly active (HA) and rapidly evolving severe (RES) RRMS are 2 forms of RRMS amenable to disease-modifying therapies (DMT). This study explored the efficacy of fingolimod relative to other DMTs for the treatment of HA and RES RRMS. METHODS: A systematic literature review (SLR) was conducted to identify published randomised controlled trials in HA and RES RRMS...
March 10, 2017: BMJ Open
https://www.readbyqxmd.com/read/28283109/classifying-pml-risk-with-disease-modifying-therapies
#5
REVIEW
Joseph R Berger
OBJECTIVE: To catalogue the risk of PML with the currently available disease modifying therapies (DMTs) for multiple sclerosis (MS). BACKGROUND: All DMTs perturb the immune system in some fashion. Natalizumab, a highly effective DMT, has been associated with a significant risk of PML. Fingolimod and dimethyl fumarate have also been unquestionably associated with a risk of PML in the MS population. Concerns about PML risk with other DMTs have arisen due to their mechanism of action and pharmacological parallel to other agents with known PML risk...
February 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/28260421/successful-pregnancy-after-natalizumab-associated-progressive-multifocal-leukoencephalopathy-in-a-patient-with-multiple-sclerosis
#6
Kalliopi Pitarokoili, Kerstin Hellwig, Carsten Lukas, Ralf Gold
We report the case of a post-progressive multifocal leukoencephalopathy (PML), multiple sclerosis (MS) patient with an uncomplicated pregnancy and delivery. A 28-year-old woman on natalizumab (total of 49 infusions) was diagnosed with PML due to typical magnetic resonance imaging (MRI) and clinical presentation. John Cunningham virus (JCV) was detected in the cerebrospinal fluid (CSF) during the immune reconstitution inflammatory syndrome (IRIS). Nine months after PML onset, JCV negativity in the CSF was observed...
March 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28258191/dimethyl-fumarate-selectively-reduces-memory-t-cells-and-shifts-the-balance-between-th1-th17-and-th2-in-multiple-sclerosis-patients
#7
Qi Wu, Qin Wang, Guangmei Mao, Catherine A Dowling, Steven K Lundy, Yang Mao-Draayer
Dimethyl fumarate (DMF; trade name Tecfidera) is an oral formulation of the fumaric acid ester that is Food and Drug Administration approved for treatment of relapsing-remitting multiple sclerosis. To better understand the therapeutic effects of Tecfidera and its rare side effect of progressive multifocal leukoencephalopathy, we conducted cross-sectional and longitudinal studies by immunophenotyping cells from peripheral blood (particularly T lymphocytes) derived from untreated and 4-6 and 18-26 mo Tecfidera-treated stable relapsing-remitting multiple sclerosis patients using multiparametric flow cytometry...
March 3, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28252608/-clinical-guidelines-for-the-use-of-dimethyl-fumarate-in-relapsing-remitting-multiple-sclerosis
#8
V M Alifirova, A N Boiko, Ya V Vlasov, M V Davydovskaya, M N Zakharova, N A Malkova, E V Popova, S A Sivertseva, N N Spirin, N V Khachanova, Т Е Shmidt
Multiple sclerosis is a chronic demyelinating and neurodegenerative disease of the central nervous system, in which autoimmune inflammation and oxidative stress play essential pathogenetic roles. Activation and infiltration of immune cells in brain tissues, lipid peroxidation products, mitochondrial dysfunction, defective antioxidant protection, and many other pathological factors result in demyelination, axonal injury and death, and apoptosis of oligodendrocytes and neurons, all of which causes constant progression of the disease...
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/28247911/opposing-effects-of-nrf2-and-nrf2-activating-compounds-on-the-nlrp3-inflammasome-independent-of-nrf2-mediated-gene-expression
#9
Martha Garstkiewicz, Gerhard E Strittmatter, Serena Grossi, Jennifer Sand, Gabriele Fenini, Sabine Werner, Lars E French, Hans-Dietmar Beer
The transcription factor Nrf2 regulates the expression of genes required for protection from xenobiotic and oxidative stress. Under normal conditions Nrf2 is constantly degraded upon ubiquitination, mediated by the Nrf2 inhibitor Keap1. Inflammasomes represent stress-induced protein complexes. They are critically involved in acute and chronic inflammation through caspase-1-mediated activation of pro-inflammatory cytokines. Here, we demonstrate that Nrf2 is as a positive regulator of the NLRP3 inflammasome. In contrast, Nrf2-activating compounds, including the anti-inflammatory drug dimethyl fumarate (DMF), inhibit inflammasome activation...
March 1, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28245526/progressive-multifocal-leukoencephalopathy-driven-from-rarity-to-clinical-mainstream-by-iatrogenic-immunodeficiency
#10
REVIEW
Siraj A Misbah
Advances in immune-mediated targeted therapies have proven to be a double-edged sword for patients by highlighting the risk of iatrogenic infective complications. This has been exemplified by progressive multifocal leukoencephalopathy (PML), a hitherto rare devastating viral infection of the brain caused by the neurotropic JC polyoma virus. While PML achieved prominence during the first two decades of the HIV epidemic, effective anti-retroviral treatment and restitution of T cell function has led to PML being less prominent in this population...
February 28, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28236206/glutamate-t-cells-and-multiple-sclerosis
#11
REVIEW
Mia Levite
Glutamate is the major excitatory neurotransmitter in the nervous system, where it induces multiple beneficial and essential effects. Yet, excess glutamate, evident in a kaleidoscope of acute and chronic pathologies, is absolutely catastrophic, since it induces excitotoxicity and massive loss of brain function. Both the beneficial and the detrimental effects of glutamate are mediated by a large family of glutamate receptors (GluRs): the ionotropic glutamate receptors (iGluRs) and the metabotropic glutamate receptors (mGluRs), expressed by most/all cells of the nervous system, and also by many non-neural cells in various peripheral organs and tissues...
February 24, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28217362/crystal-structure-of-dimethyl-2-2z-5z-5-2-meth-oxy-2-oxo-ethyl-idene-2-e-2-methyl-5-prop-1-en-2-yl-cyclo-hex-2-enyl-idene-hydrazinyl-idene-4-oxo-thia-zolidin-3-yl-fumarate
#12
Abdellah N'ait Ousidi, My Youssef Ait Itto, Aziz Auhmani, Abdelkhalek Riahi, Abdelwahed Auhmani, Jean-Claude Daran
The crystal structure and the conformation of the title compound, C22H27N3O7S, were determined from the synthetic pathway and by X-ray analysis. This compound is a new 4-thia-zolidinone derivative prepared and isolated as pure product from thio-semicarbazone carvone. The mol-ecule is built up from an oxo-thia-zolidine ring tetra-substituted by a meth-oxy-oxo-ethyl-idene, a maleate, an oxygen and a cyclo-hexyl-idene-hydrazone. The cyclo-hexyl-idene ring is statistically disordered over two positions, resulting in an inversion of configuration for the substituted carbon...
February 1, 2017: Acta Crystallographica. Section E, Crystallographic Communications
https://www.readbyqxmd.com/read/28211024/comparative-effectiveness-research-of-disease-modifying-therapies-for-the-management-of-multiple-sclerosis-analysis-of-a-large-health-insurance-claims-database
#13
Aaron Boster, Jacqueline Nicholas, Ning Wu, Wei-Shi Yeh, Monica Fay, Michael Edwards, Ming-Yi Huang, Andrew Lee
INTRODUCTION: Limited data are available on the real-world effectiveness of newer oral disease-modifying therapies (DMTs) in multiple sclerosis. The purpose of this study was to retrospectively compare the real-world effectiveness of dimethyl fumarate (DMF), fingolimod, teriflunomide, and injectable DMTs in routine clinical practice based on US claims data. METHODS: Patients newly-initiating DMF, interferon beta (IFNβ), glatiramer acetate (GA), teriflunomide, or fingolimod in 2013 were identified in the Truven MarketScan Commercial Claims Databases (N = 6372)...
February 16, 2017: Neurology and Therapy
https://www.readbyqxmd.com/read/28209921/dimethyl-fumarate-for-ischemic-stroke
#14
EDITORIAL
Reiner Kunze
No abstract text is available yet for this article.
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28209373/cost-utility-of-first-line-disease-modifying-treatments-for-relapsing-remitting-multiple-sclerosis
#15
Erkki Soini, Jaana Joutseno, Marja-Liisa Sumelahti
PURPOSE: This study evaluated the cost-effectiveness of first-line treatments of relapsing-remitting multiple sclerosis (RRMS) (dimethyl fumarate [DMF] 240 mg PO BID, teriflunomide 14 mg once daily, glatiramer acetate 20 mg SC once daily, interferon [IFN]-β1a 44 µg TIW, IFN-β1b 250 µg EOD, and IFN-β1a 30 µg IM QW) and best supportive care (BSC) in the health care payer setting in Finland. METHODS: The primary outcome was the modeled incremental cost-effectiveness ratio (ICER; €/quality-adjusted life-year [QALY] gained, 3%/y discounting)...
February 13, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28181536/the-nrf2-transcriptional-target-osgin1-contributes-to-monomethyl-fumarate-mediated-cytoprotection-in-human-astrocytes
#16
Melanie S Brennan, Maria F Matos, Karl E Richter, Bing Li, Robert H Scannevin
Dimethyl fumarate (DMF) is indicated for the treatment of relapsing multiple sclerosis and may exert therapeutic effects via activation of the nuclear factor (erythroid-derived 2)-like 2 (NRF2) pathway. Following oral DMF administration, central nervous system (CNS) tissue is predominantly exposed to monomethyl fumarate (MMF), the bioactive metabolite of DMF, which can stabilize NRF2 and induce antioxidant gene expression; however, the detailed NRF2-dependent mechanisms modulated by MMF that lead to cytoprotection are unknown...
February 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28180112/oral-multiple-sclerosis-drugs-inhibit-the-in-vitro-growth-of-epsilon-toxin-producing-gut-bacterium-clostridium-perfringens
#17
Kareem R Rumah, Timothy K Vartanian, Vincent A Fischetti
There are currently three oral medications approved for the treatment of multiple sclerosis (MS). Two of these medications, Fingolimod, and Teriflunomide, are considered to be anti-inflammatory agents, while dimethyl fumarate (DMF) is thought to trigger a robust antioxidant response, protecting vulnerable cells during an MS attack. We previously proposed that epsilon toxin from the gut bacterium, Clostridium perfringens, may initiate newly forming MS lesions due to its tropism for blood-brain barrier (BBB) vasculature and central nervous system myelin...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28161400/memory-b-cells-are-major-targets-for-effective-immunotherapy-in-relapsing-multiple-sclerosis
#18
REVIEW
David Baker, Monica Marta, Gareth Pryce, Gavin Giovannoni, Klaus Schmierer
Although multiple sclerosis (MS) is considered to be a CD4, Th17-mediated autoimmune disease, supportive evidence is perhaps circumstantial, often based on animal studies, and is questioned by the perceived failure of CD4-depleting antibodies to control relapsing MS. Therefore, it was interestingly to find that current MS-treatments, believed to act via T cell inhibition, including: beta-interferons, glatiramer acetate, cytostatic agents, dimethyl fumarate, fingolimod, cladribine, daclizumab, rituximab/ocrelizumab physically, or functionally in the case of natalizumab, also depleted CD19+, CD27+ memory B cells...
February 2017: EBioMedicine
https://www.readbyqxmd.com/read/28157295/vitamin-derived-nanolipoidal-carriers-for-brain-delivery-of-dimethyl-fumarate-a-novel-approach-with-preclinical-evidences
#19
Pramod Kumar, Gajanand Sharma, Rajendra Kumar, Ruchi Malik, Bhupinder Singh, O P Katare, Kaisar Raza
Various oral treatment options have been reported for relapsing multiple sclerosis. Recently, dimethyl fumarate (DMF) has been approved for the management of the same. Though effective, DMF is associated with concerns like multiple dosing, patient incompliance, gastrointestinal flushing, lower brain permeation and economic hurdles. Henceforth, the objective of the present study was to develop vitamin-based solid lipid nanoparticles (SLNs) for effective brain delivery of DMF with a promise of once-a-day dosing...
February 3, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28156185/evidence-of-activation-of-the-nrf2-pathway-in-multiple-sclerosis-patients-treated-with-delayed-release-dimethyl-fumarate-in-the-phase-3-define-and-confirm-studies
#20
Sreeja Gopal, Alvydas Mikulskis, Ralf Gold, Robert J Fox, Katherine T Dawson, Lakshmi Amaravadi
BACKGROUND: Delayed-release dimethyl fumarate (DMF) is an approved oral treatment for relapsing forms of multiple sclerosis (MS). Preclinical studies demonstrated that DMF activated the nuclear factor E2-related factor 2 (Nrf2) pathway. DMF and its primary metabolite monomethyl fumarate (MMF) were also shown to promote cytoprotection of cultured central nervous system (CNS) cells via the Nrf2 pathway. OBJECTIVE: To investigate the activation of Nrf2 pathway following ex vivo stimulation of human peripheral blood mononuclear cells (PBMCs) with DMF or MMF, and in DMF-treated patients from two Phase 3 relapsing MS studies DEFINE and CONFIRM...
January 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
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