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Fumarate dimethyl

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https://www.readbyqxmd.com/read/29764226/oral-disease-modifying-therapies-for-multiple-sclerosis-in-the-middle-eastern-and-north-african-mena-region-an-overview
#1
Dirk Deleu, Boulenouar Mesraoua, Beatriz Canibaño, Gayane Melikyan, Hassan Al Hail, Lubna El-Sheikh, Musab Ali, Hassan Al Hussein, Faiza Ibrahim, Yolande Hanssens
The introduction of new disease-modifying therapies (DMTs) for remitting-relapsing multiple sclerosis (RRMS) have considerably transformed the landscape of therapeutic opportunities for this chronic disabling disease. Unlike injectable drugs, oral DMTs, promote patient satisfaction and increase therapeutic adherence. This article reviews the salient features about the mode of action, efficacy, safety and tolerability profile of approved oral DMTs in RRMS and reviews their place in clinical algorithms in the Middle East and North Africa (MENA) region...
May 15, 2018: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/29763776/dimethyl-fumarate-downregulates-the-immune-response-through-the-hca-2-gpr109a-pathway-implications-for-the-treatment-of-multiple-sclerosis
#2
REVIEW
Felipe von Glehn, Rafael P C Dias-Carneiro, Adriel S Moraes, Alessandro S Farias, Veronica A P G Silva, Francisco T M Oliveira, Carlos Eduardo B G Silva, Fabricio de Carvalho, Elaine Rahal, Clare Baecher-Allan, Leonilda M B Santos
BACKGROUND: The mechanisms of action of dimethyl fumarate (DMF), and its metabolite, monomethyl fumarate (MMF), for the treatment of multiple sclerosis are not completely elucidated. OBJECTIVES: To discuss the role of DMF/MMF-induced hydroxycarboxylic acid receptor 2 (HCA2 /GPR109A) pathway activation in the immune response and treatment of MS. METHODS: A narrative (traditional) review of the current literature. RESULTS: Studies have shown that binding of DMF/MMF to HCA2 on dendritic cells inhibits the production of pro-inflammatory cytokines in vitro and in MS murine models...
April 25, 2018: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/29744572/protective-potential-of-dimethyl-fumarate-in-a-mouse-model-of-thalamocortical-demyelination
#3
Manuela Cerina, Venu Narayanan, Anna Delank, Patrick Meuth, Stephanie Graebenitz, Kerstin Göbel, Alexander M Herrmann, Stefanie Albrecht, Thiemo Daldrup, Thomas Seidenbecher, Ali Gorji, Tanja Kuhlmann, Heinz Wiendl, Christoph Kleinschnitz, Erwin J Speckmann, Hans-Christian Pape, Sven G Meuth, Thomas Budde
Alterations in cortical cellular organization, network functionality, as well as cognitive and locomotor deficits were recently suggested to be pathological hallmarks in multiple sclerosis and corresponding animal models as they might occur following demyelination. To investigate functional changes following demyelination in a well-defined, topographically organized neuronal network, in vitro and in vivo, we focused on the primary auditory cortex (A1) of mice in the cuprizone model of general de- and remyelination...
May 9, 2018: Brain Structure & Function
https://www.readbyqxmd.com/read/29713994/dimethyl-fumarate-limits-neuroinflammation-and-oxidative-stress-and-improves-cognitive-impairment-after-polymicrobial-sepsis
#4
Graciela Freitas Zarbato, Mariana Pereira de Souza Goldim, Amanda Della Giustina, Lucinéia Gainski Danielski, Khiany Mathias, Drielly Florentino, Aloir Neri de Oliveira Junior, Naiana da Rosa, Ana Olivia Laurentino, Taina Trombetta, Maria Luiza Gomes, Amanda Valnier Steckert, Ana Paula Moreira, Patricia Fernanda Schuck, Jucelia Jeremias Fortunato, Tatiana Barichello, Fabricia Petronilho
Sepsis is caused by a dysregulated host response to infection, often associated with acute central nervous system (CNS) dysfunction, which results in long-term cognitive impairment. Dimethyl fumarate (DMF) is an important agent against inflammatory response and reactive species in CNS disorders. Evaluate the effect of DMF on acute and long-term brain dysfunction after experimental sepsis in rats. Male Wistar rats were submitted to the cecal ligation and puncture (CLP) model. The groups were divided into sham (control) + vehicle, sham + NAC, sham + DMF, CLP + vehicle, CLP + NAC, and CLP + DMF...
April 30, 2018: Neurotoxicity Research
https://www.readbyqxmd.com/read/29709955/disease-exacerbation-after-the-cessation-of-fingolimod-treatment-in-japanese-patients-with-multiple-sclerosis
#5
Kazunori Sato, Masaaki Niino, Atsushi Kawashima, Moemi Yamada, Yusei Miyazaki, Toshiyuki Fukazawa
Objective In Japan, following the launch of dimethyl fumarate (DMF) after fingolimod as a disease-modifying drug in multiple sclerosis (MS), some patients switched from fingolimod to DMF. The aim of this study was to determine the follow-up status of MS patients who switched to DMF after fingolimod cessation. Methods Clinical and magnetic resonance imaging (MRI) data in 19 patients with MS who switched to DMF were collected for at least for 6 months after fingolimod cessation. Results Ten patients (52.6%) experienced clinical or MRI exacerbation after fingolimod cessation...
April 27, 2018: Internal Medicine
https://www.readbyqxmd.com/read/29708444/fulminant-rebound-of-relapsing-remitting-multiple-sclerosis-after-discontinuation-of-dimethyl-fumarate-a-case-report
#6
Peter Harmel, Frieder Schlunk, Lutz Harms
BACKGROUND: Rebound phenomena after discontinuation of different treatments for relapsing-remitting multiple sclerosis (RRMS) have previously been described. Systematic database research in PubMed did not show any report with relapse directly associated with dimethyl fumarate (DMF) cessation. CASE PRESENTATION: Here, we report on a 38-year-old Caucasian male patient suffering from a relatively mild course of RRMS who developed a fulminant clinical rebound 2 months after discontinuation of DMF therapy...
April 1, 2018: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/29707040/incidence-and-mitigation-of-gastrointestinal-events-in-patients-with-relapsing-remitting-multiple-sclerosis-receiving-delayed-release-dimethyl-fumarate-a-german-phase-iv-study-tolerate
#7
Ralf Gold, Eugen Schlegel, Birte Elias-Hamp, Christian Albert, Stephan Schmidt, Björn Tackenberg, James Xiao, Tom Schaak, Hans Christian Salmen
Background: Gastrointestinal (GI) events are common adverse events (AEs) associated with delayed-release dimethyl fumarate (DMF), an approved treatment for relapsing-remitting multiple sclerosis (RRMS). The objective of the TOLERATE study was to evaluate GI tolerability and GI mitigation via symptomatic therapies in patients initiating DMF in a real-world clinical setting in Germany. Methods: TOLERATE was a multicentre, open-label, single-arm study performed at 25 German sites...
2018: Therapeutic Advances in Neurological Disorders
https://www.readbyqxmd.com/read/29703445/first-line-therapy-in-relapsing-remitting-multiple-sclerosis
#8
REVIEW
D Biotti, J Ciron
Today, first-line treatments for multiple sclerosis include injectable immunomodulators - some of which have been on the market for nearly 25 years - as well as teriflunomide and dimethyl fumarate, which are more recent, but have opened the way for oral treatments. These drugs are considered similar in effectiveness, and their safety and side-effect profiles are generally reassuring. These treatments have been associated with a reduction in radiological and clinical disease activity, and a positive effect on patient quality of life, especially when introduced early in the disease process...
April 24, 2018: Revue Neurologique
https://www.readbyqxmd.com/read/29695598/preapproval-and-postapproval-evidence-on-drugs-for-multiple-sclerosis
#9
REVIEW
Chiara Gerardi, Vittorio Bertele', Silvia Rossi, Silvio Garattini, Rita Banzi
OBJECTIVE: To review the evidence supporting the European Union marketing authorization of drugs for multiple sclerosis (MS) and assess how far postmarketing research addresses information gaps at the time of approval. METHODS: Through its database, we identified drugs approved by the European Medicines Agency and gathered data on pivotal trials from the European Public Assessment Reports and corresponding publications. We searched Medline, Embase, Cochrane Library, and trial registries for postmarketing randomized controlled trials testing the drugs identified in any form of the disease...
April 25, 2018: Neurology
https://www.readbyqxmd.com/read/29691120/neuroprotective-effect-of-nrf2-activator-dimethyl-fumarate-on-the-hippocampal-neurons-in-chemical-kindling-model-in-rat
#10
Neha Singh, Sheekha Vijayanti, Lekha Saha, Alka Bhatia, Dibyajyoti Banerjee, Amitava Chakrabarti
BACKGROUND: Nuclear factor erythroid-2 related factor 2 (Nrf2) is a transcription factor, which activates the anti-oxidative stress response pathway. In epilepsy, oxidative stress is one of the key factors in the progression of the disease. So, the neuroprotective role of dimethyl fumarate (DMF), a Nrf2 pathway activator was explored in pentylenetetrazole (PTZ) induced kindling model of epilepsy in rats. METHODS: Male Wistar rats were subjected to different doses of DMF (15, 30, 60 mg/kg) to evaluate the effect on the PTZ induced kindling in rats...
April 21, 2018: Epilepsy Research
https://www.readbyqxmd.com/read/29686116/practice-guideline-recommendations-summary-disease-modifying-therapies-for-adults-with-multiple-sclerosis-report-of-the-guideline-development-dissemination-and-implementation-subcommittee-of-the-american-academy-of-neurology
#11
Alexander Rae-Grant, Gregory S Day, Ruth Ann Marrie, Alejandro Rabinstein, Bruce A C Cree, Gary S Gronseth, Michael Haboubi, June Halper, Jonathan P Hosey, David E Jones, Robert Lisak, Daniel Pelletier, Sonja Potrebic, Cynthia Sitcov, Rick Sommers, Julie Stachowiak, Thomas S D Getchius, Shannon A Merillat, Tamara Pringsheim
OBJECTIVE: To develop recommendations for disease-modifying therapy (DMT) for multiple sclerosis (MS). METHODS: A multidisciplinary panel developed DMT recommendations, integrating findings from a systematic review; followed an Institute of Medicine-compliant process to ensure transparency and patient engagement; and developed modified Delphi consensus-based recommendations concerning starting, switching, and stopping DMTs pertinent to people with relapsing-remitting MS, secondary progressive MS, primary progressive MS, and clinically isolated syndromes of demyelination...
April 24, 2018: Neurology
https://www.readbyqxmd.com/read/29684504/schwann-cell-plasticity-is-regulated-by-a-weakened-intrinsic-antioxidant-defense-system-in-acute-peripheral-nerve-injury
#12
Wenjing Lv, Binbin Deng, Weisong Duan, Yuanyuan Li, Yakun Liu, Zhongyao Li, Wei Xia, Chunyan Li
The biological effects of the transcription factor NF-E2-related factor 2 (Nrf2) in acute peripheral nervous system (PNS) injury have not been adequately elucidated. By analyzing the results of Nrf2 knockout and Nrf2 activation experiments, we found the following: (1) The antioxidant system was rapidly inactivated after acute PNS injury in a partly Nrf2-dependent manner, giving rise to a temporary state of oxidative stress, and then slowly and partially recovered following regeneration. (2) Nrf2 knockout promoted the reprogramming and proliferation of Schwann cells and inhibited myelination, as well as the redifferentiation of repair Schwann cells...
April 20, 2018: Neuroscience
https://www.readbyqxmd.com/read/29681490/safety-and-efficacy-of-delayed-release-dimethyl-fumarate-in-pediatric-patients-with-relapsing-multiple-sclerosis-focus
#13
Raed Alroughani, Rajiv Das, Natasha Penner, Joe Pultz, Catherine Taylor, Satish Eraly
BACKGROUND: No therapies have been formally approved by the Food and Drug Administration for use in pediatric multiple sclerosis, a rare disease. OBJECTIVE: We evaluated the safety, efficacy, and pharmacokinetics of dimethyl fumarate in pediatric patients with multiple sclerosis. METHODS: FOCUS, a phase 2, multicenter study of patients aged 10 to 17 years with relapsing-remitting multiple sclerosis, comprised an eight-week baseline and 24-week treatment period; during treatment, patients received dimethyl fumarate (120 mg twice daily on days one to seven; 240 mg twice a day thereafter)...
March 22, 2018: Pediatric Neurology
https://www.readbyqxmd.com/read/29675414/spondyloarthritis-acute-anterior-uveitis-and-fungi-updating-the-catterall-king-hypothesis
#14
Martin Laurence, Mark Asquith, James T Rosenbaum
Spondyloarthritis is a common type of arthritis which affects mostly adults. It consists of idiopathic chronic inflammation of the spine, joints, eyes, skin, gut, and prostate. Inflammation is often asymptomatic, especially in the gut and prostate. The HLA-B*27 allele group, which presents intracellular peptides to CD8+ T cells, is by far the strongest risk factor for spondyloarthritis. The precise mechanisms and antigens remain unknown. In 1959, Catterall and King advanced a novel hypothesis explaining the etiology of spondyloarthritis: an as-yet-unrecognized sexually acquired microbe would be causing all spondyloarthritis types, including acute anterior uveitis...
2018: Frontiers in Medicine
https://www.readbyqxmd.com/read/29663814/new-biological-agents-in-the-treatment-of-multiple-sclerosis
#15
M Buc
Multiple sclerosis (MS) is an inflammatory disease induced by autoimmune processes. Their understanding has resulted in an introduction of biological agents to its treatment. Interferon beta and glatiramer acetate have been in clinical practice for more than 20 years. Nowadays, novel biologics, which target molecules involved in immunopathological processes more specifically have entered the scene. They are represented by monoclonal antibodies binding to molecules VLA4 (natalizumab), CD20 (ocrelizumab), CD52 (alemtuzumab) or alpha subunit of IL-2 receptor (daclizumab) or by small molecules such as those modulating the receptors involved in regulation of lymphocyte migration (fingolimod, ozanimod) or in induction of lymphopenia by apoptosis (dimethyl fumarate, cladribine)...
2018: Bratislavské Lekárske Listy
https://www.readbyqxmd.com/read/29649923/diffuse-dermatophytosis-occurring-on-dimethyl-fumarate-therapy
#16
Jeffrey I Greenstein
BACKGROUND: Opportunistic infections have occurred during dimethyl fumarate (DMF) therapy. OBJECTIVE: Diffuse skin dermatophytosis which occurred during DMF therapy in the setting of lymphopenia is described. METHODS AND RESULTS: The clinical course, the lymphocyte subset profile, and dermatologic evaluations were reviewed. In both instances, there was no other cause of lymphopenia or immune suppression, and it is likely that the tinea infections are associated with DMF therapy...
April 1, 2018: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/29610843/listeria-monocytogenes-induced-rhombencephalitis-in-a-patient-with-multiple-sclerosis-treated-with-dimethyl-fumarate
#17
Serena Ruggieri, Alessandra Logoteta, Gabriella Martini, Alessandro Bozzao, Laura De Giglio
No abstract text is available yet for this article.
April 2, 2018: JAMA Neurology
https://www.readbyqxmd.com/read/29600441/efficacy-and-safety-of-the-newer-multiple-sclerosis-drugs-approved-since-2010
#18
REVIEW
Simon Faissner, Ralf Gold
Multiple sclerosis treatment faces tremendous changes as a result of the approval of new medications. The new medications have differing safety considerations and risks after long-term treatment, which are important for treating physicians to optimize and individualize multiple sclerosis care. Since the approval of the first multiple sclerosis capsule, fingolimod, the armamentarium of multiple sclerosis therapy has grown with the orally available medications dimethyl fumarate and teriflunomide. Fingolimod is mainly associated with cardiac side effects, dimethyl fumarate with bowel symptoms...
March 2018: CNS Drugs
https://www.readbyqxmd.com/read/29599194/dimethyl-fumarate-targets-gapdh-and-aerobic-glycolysis-to-modulate-immunity
#19
Michael D Kornberg, Pavan Bhargava, Paul M Kim, Vasanta Putluri, Adele M Snowman, Nagireddy Putluri, Peter A Calabresi, Solomon H Snyder
Activated immune cells undergo a metabolic switch to aerobic glycolysis akin to the Warburg effect, thereby presenting a potential therapeutic target in autoimmune disease. Dimethyl fumarate (DMF), a derivative of the Krebs cycle intermediate fumarate, is an immunomodulatory drug used to treat multiple sclerosis and psoriasis. Although its therapeutic mechanism remains uncertain, DMF covalently modifies cysteine residues in a process termed succination. We found that DMF succinates and inactivates the catalytic cysteine of the glycolytic enzyme glyceraldehyde 3-phosphate dehydrogenase (GAPDH) in mice and humans, both in vitro and in vivo...
April 27, 2018: Science
https://www.readbyqxmd.com/read/29598822/dimethyl-fumarate-attenuates-reactive-microglia-and-long-term-memory-deficits-following-systemic-immune-challenge
#20
Hallel C Paraiso, Ping-Chang Kuo, Eric T Curfman, Haley J Moon, Robert D Sweazey, Jui-Hung Yen, Fen-Lei Chang, I-Chen Yu
BACKGROUND: Systemic inflammation is associated with increased cognitive decline and risk for Alzheimer's disease. Microglia (MG) activated during systemic inflammation can cause exaggerated neuroinflammatory responses and trigger progressive neurodegeneration. Dimethyl fumarate (DMF) is a FDA-approved therapy for multiple sclerosis. The immunomodulatory and anti-oxidant properties of DMF prompted us to investigate whether DMF has translational potential for the treatment of cognitive impairment associated with systemic inflammation...
March 29, 2018: Journal of Neuroinflammation
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