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Fumarate dimethyl

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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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...
January 31, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28157295/vitamin-derived-nanolipoidal-carriers-for-brain-delivery-of-dimethyl-fumarate-a-novel-approach-with-preclinical-evidences
#8
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
#9
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
https://www.readbyqxmd.com/read/28150703/dimethyl-fumarate-ameliorates-pulmonary-arterial-hypertension-and-lung-fibrosis-by-targeting-multiple-pathways
#10
Agnieszka P Grzegorzewska, Francesca Seta, Rong Han, Caitlin A Czajka, Katsunari Makino, Lukasz Stawski, Jeffrey S Isenberg, Jeffrey L Browning, Maria Trojanowska
Pulmonary arterial hypertension (PAH) is a fatal condition for which there is no cure. Dimethyl Fumarate (DMF) is an FDA approved anti-oxidative and anti-inflammatory agent with a favorable safety record. The goal of this study was to assess the effectiveness of DMF as a therapy for PAH using patient-derived cells and murine models. We show that DMF treatment is effective in reversing hemodynamic changes, reducing inflammation, oxidative damage, and fibrosis in the experimental models of PAH and lung fibrosis...
February 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28134847/dimethyl-fumarate-therapy-significantly-improves-the-responsiveness-of-t-cells-in-multiple-sclerosis-patients-for-immunoregulation-by-regulatory-t-cells
#11
Janine Schlöder, Carsten Berges, Felix Luessi, Helmut Jonuleit
Multiple sclerosis (MS) is a chronic autoimmune disease caused by an insufficient suppression of autoreactive T lymphocytes. One reason for the lack of immunological control is the reduced responsiveness of T effector cells (Teff) for the suppressive properties of regulatory T cells (Treg), a process termed Treg resistance. Here we investigated whether the disease-modifying therapy of relapsing-remitting MS (RRMS) with dimethyl fumarate (DMF) influences the sensitivity of T cells in the peripheral blood of patients towards Treg-mediated suppression...
January 28, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28130920/interdisciplinary-risk-management-in-the-treatment-of-multiple-sclerosis
#12
Joachim Havla, Clemens Warnke, Tobias Derfuss, Ludwig Kappos, Hans-Peter Hartung, Reinhard Hohlfeld
BACKGROUND: Multiple sclerosis (MS) is the most common autoimmune disease of the central nervous system. There are at least 150 000 persons with MS in Germany. Recent years have seen the approval of new drugs against. METHODS: This article is based on pertinent literature retrieved by a selective search in PubMed as well as on documentation of relevant risks and adverse effects in "red hand letters" (information bulletins from pharmaceutical companies to physicians about adverse drug effects) and elsewhere, along with data provided by the German Multiple Sclerosis Competence Network...
December 26, 2016: Deutsches Ärzteblatt International
https://www.readbyqxmd.com/read/28130412/update-on-disease-modifying-therapies-for-multiple-sclerosis
#13
Diana L Vargas, William R Tyor
Multiple sclerosis (MS) is an autoimmune, demyelinating disease of the central nervous system (CNS). It predominantly affects young women and is one of the most common causes of disability in young adults. MS is characterized by formation of white matter lesions in the CNS as a result of inflammation, demyelination, and axonal loss. Treatment has been a focus of neurological research for over 60 years. A number of disease-modifying therapies (DMTs) have become available making MS a treatable disease. These compounds target the inflammatory response in MS...
January 27, 2017: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
https://www.readbyqxmd.com/read/28116039/dimethyl-fumarate-induces-glutathione-recycling-by-upregulation-of-glutathione-reductase
#14
Christina Hoffmann, Michael Dietrich, Ann-Kathrin Herrmann, Teresa Schacht, Philipp Albrecht, Axel Methner
Neuronal degeneration in multiple sclerosis has been linked to oxidative stress. Dimethyl fumarate (DMF) is an effective oral therapeutic option shown to reduce disease activity and progression in patients with relapsing-remitting multiple sclerosis. DMF activates the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) leading to increased synthesis of the major cellular antioxidant glutathione (GSH) and prominent neuroprotection in vitro. We previously demonstrated that DMF is capable of raising GSH levels even when glutathione synthesis is inhibited, suggesting enhanced GSH recycling...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28104252/novel-zebrafish-eae-model-a-quick-in-vivo-screen-for-multiple-sclerosis
#15
Pushkar Kulkarni, Swapna Yellanki, Raghavender Medishetti, Dharmarajan Sriram, Uday Saxena, Perumal Yogeeswari
INTRODUCTION: Pre-clinical drug discovery for multiple sclerosis (MS) is a labor intensive activity to perform in rodent models. This is owing to the long duration of disease induction and observation of treatment effects in an experimental autoimmune encephalomyelitis (EAE) model. We propose a novel adult zebrafish based model which offers a quick and simple protocol that can used to screen candidates as a step between in vitro experiments and rodent studies. The experiments conducted for this manuscript were to standardize a suitable model of EAE in adult zebrafish and validate it using known modulators...
January 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/28093681/quantifying-the-benefits-of-dimethyl-fumarate-over-%C3%AE-interferon-and-glatiramer-acetate-therapies-on-work-productivity-outcomes-in-ms-patients
#16
Andrew Lee, James Pike, Michael R Edwards, Jennifer Petrillo, John Waller, Eddie Jones
INTRODUCTION: Dimethyl fumarate (DMF) is a novel oral therapy used for the treatment of relapse-remitting multiple sclerosis (RRMS). In two 2-year pivotal Phase 3 trials in patients with RRMS, DMF significantly reduced disease activity based on both clinical and magnetic resonance imaging (MRI) findings and demonstrated an acceptable safety profile. However, there is currently a lack of comparative data which explore the relationship between work productivity and health-related quality of life (HRQoL) outcomes in RRMS and how these differ among RRMS therapies, including DMF...
January 16, 2017: Neurology and Therapy
https://www.readbyqxmd.com/read/28092423/-1-h-qnmr-quantification-of-annonaceous-acetogenins-in-crude-extracts-of-annona-muricata-l-fruit-pulp
#17
Natacha Bonneau, Timothé Cynober, Jean-Christophe Jullian, Pierre Champy
INTRODUCTION: Annonaceous acetogenins (AAGs) constitute a group of environmental neurotoxins, possibly implicated in sporadic atypical Parkinsonism/dementia complexes. The recent evidencing of complex mixtures of AAGs in edible fruits and derived food products requires efficient and practical analytical tools for an estimation of human exposure. OBJECTIVE: To develop a simple method for the direct quantitation of the majority of AAGs (sub-types 1a and 1b) within crude extracts, using commonly available (1) H-NMR spectrometers, for food control...
January 16, 2017: Phytochemical Analysis: PCA
https://www.readbyqxmd.com/read/28069874/dimethyl-fumarate-controls-the-nrf2-dj-1-axis-in-cancer-cells-therapeutic-applications
#18
Nathaniel Edward Bennett Saidu, Gaëlle Noé, Olivier Cerles, Luc Cabel, Niloufar Kavian-Tessler, Sandrine Chouzenoux, Mathilde Bahuaud, Christiane Chéreau, Carole Nicco, Karen Leroy, Bruno Borghese, Francois Goldwasser, Frédéric Batteux, Jerome Alexandre
The transcription factor NRF2 (NFE2L2), regulates important antioxidant and cytoprotective genes. It enhances cancer cell proliferation and promotes chemoresistance in several cancers. Dimethyl fumarate (DMF) is known to promote NRF2 activity in non-cancer models. We combined in vitro and in vivo methods to examine the effect of DMF on cancer cell death and the activation of the NRF2 antioxidant pathway. We demonstrated that at lower concentrations (< 25 μM), DMF has a cytoprotective role through activation of the NRF2 antioxidant pathway...
January 9, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28063629/the-autoimmune-risk-gene-zmiz1-is-a-vitamin-d-responsive-marker-of-a-molecular-phenotype-of-multiple-sclerosis
#19
N L Fewings, P N Gatt, F C McKay, G P Parnell, S D Schibeci, J Edwards, M A Basuki, A Goldinger, M J Fabis-Pedrini, A G Kermode, C P Manrique, J L McCauley, D Nickles, S E Baranzini, T Burke, S Vucic, G J Stewart, D R Booth
Multiple Sclerosis (MS) is a neurological condition driven in part by immune cells from the peripheral circulation, the targets for current successful therapies. The autoimmune and MS risk gene ZMIZ1 is underexpressed in blood in people with MS. We show that, from three independent sets of transcriptomic data, expression of ZMIZ1 is tightly correlated with that of hundreds of other genes. Further we show expression is partially heritable (heritability 0.26), relatively stable over time, predominantly in plasmacytoid dendritic cells and non-classical monocytes, and that levels of ZMIZ1 protein expression are reduced in MS...
January 4, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28059711/t1-recovery-is-predominantly-found-in-black-holes-and-is-associated-with-clinical-improvement-in-patients-with-multiple-sclerosis
#20
C Thaler, T D Faizy, J Sedlacik, B Holst, K Stürner, C Heesen, J-P Stellmann, J Fiehler, S Siemonsen
BACKGROUND AND PURPOSE: Quantitative MR imaging parameters help to evaluate disease progression in multiple sclerosis and increase correlation with clinical disability. We therefore hypothesized that T1 values might be a marker for ongoing tissue damage or even remyelination and may help increase clinical correlation. MATERIALS AND METHODS: MR imaging was performed in 17 patients with relapsing-remitting MS at baseline and after 12 months of starting immunotherapy with dimethyl fumarate...
November 10, 2016: AJNR. American Journal of Neuroradiology
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