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Fumarate dimethyl

Bhupendra O Khatri, Sergey S Tarima, Benjamin Essig, Jean Sesing, Tayo Olapo
BACKGROUND: Dimethyl fumarate (DMF) reduces absolute lymphocyte counts, CD4, and CD8 counts, without significantly affecting total white blood cell counts. However, the recovery rate of these cells after discontinuation of DMF is unknown. The effect of subsequent disease modifying therapies (DMTs) on re-population rate is also unknown. OBJECTIVES: 1. To study the re-population rate of absolute lymphocytes, CD4, and CD8 counts back to baseline after discontinuation of DMF...
November 2017: Multiple Sclerosis and related Disorders
Tessa Eagle, Fiona Stuart, Alicia S Chua, Allison LaRussa, Kaitlynne Leclaire, Sandra L Cook, Tanuja Chitnis, Howard L Weiner, Bonnie I Glanz, Brian C Healy
BACKGROUND: The recent approval of oral disease-modifying therapies (DMTs) for multiple sclerosis (MS) has provided patients with a new route of therapy administration. Little research has compared patients' experiences with and perceptions of injectable, infusion and oral MS therapies. METHODS: Three hundred fifty-seven treated MS patients enrolled in the CLIMB study completed the Treatment Satisfaction Questionnaire for Medication (TSQM). The TSQM provides information regarding perceived effectiveness, side effects, convenience and overall satisfaction...
November 2017: Multiple Sclerosis and related Disorders
Irene Eriksson, Thomas Cars, Fredrik Piehl, Rickard E Malmström, Björn Wettermark, Mia von Euler
PURPOSE: To describe patients initiating dimethyl fumarate (DMF) and measure persistence with DMF, discontinuation, and switching in treatment-naïve DMF patients and patients switching to DMF from other multiple sclerosis disease-modifying treatments (DMTs). METHODS: A population-based cohort study of all Stockholm County residents initiating DMF from 9 May 2014 until 31 May 2017. All data were derived from a regional database that collects individual-level data on healthcare and drug utilization of all residents...
November 11, 2017: European Journal of Clinical Pharmacology
Amanda Della Giustina, Sandra Bonfante, Graciela Freitas Zarbato, Lucinéia Gainski Danielski, Khiany Mathias, Aloir Neri de Oliveira, Leandro Garbossa, Taise Cardoso, Maria Eduarda Fileti, Raquel Jaconi De Carli, Mariana Pereira Goldim, Tatiana Barichello, Fabricia Petronilho
Sepsis is defined as life-threatening organ dysfunction induced by a disrupted host response to infecting pathogens. Evidences suggest that oxidative stress is intrinsically related to sepsis progression. Dimethyl fumarate (DMF) is a novel oral therapeutic agent with anti-oxidant properties which exerts protective effects through activation of nuclear factor erythroid 2 (NFE2)-related factor 2 (Nrf2). Thus, the aim of this study is to evaluate the effect of DMF in different organs of rats submitted to an animal model of sepsis...
November 9, 2017: Inflammation
Antonio Cuadrado, Sebastian Kügler, Isabel Lastres-Becker
Tauopathies are a group of neurodegenerative disorders where TAU protein is presented as aggregates or is abnormally phosphorylated, leading to alterations of axonal transport, neuronal death and neuroinflammation. Currently, there is no treatment to slow progression of these diseases. Here, we have investigated whether dimethyl fumarate (DMF), an inducer of the transcription factor NRF2, could mitigate tauopathy in a mouse model. The signaling pathways modulated by DMF were also studied in mouse embryonic fibroblast (MEFs) from wild type or KEAP1-deficient mice...
November 6, 2017: Redox Biology
Maria Antonietta Mazzola, Radhika Raheja, Keren Regev, Vanessa Beynon, Felipe von Glehn, Anu Paul, Isabelle Pierre, Pia Kivisakk, Howard L Weiner, Roopali Gandhi
BACKGROUND: Dimethyl fumarate (DMF) and its active metabolite monomethyl fumarate (MMF) effectively lead to reduction in disease relapses and active magnetic resonance imaging (MRI) lesions. DMF and MMF are known to be effective in modulating T- and B-cell responses; however, their effect on the phenotype and function of human myeloid dendritic cells (mDCs) is not fully understood. OBJECTIVE: To investigate the role of MMF on human mDCs maturation and function. METHODS: mDCs from healthy controls were isolated and cultured in vitro with MMF...
November 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
Sarah E Fiedler, Amelia R Kerns, Catherine Tsang, Haley N Love, Sonemany Salinthone
OBJECTIVE: Dimethyl fumarate (DMF) is an anti-inflammatory and antioxidant drug used to treat multiple sclerosis, but its mechanism(s) of action are not fully understood. In central nervous system (CNS) cells, DMF activates nuclear factor E2-related factor 2 (Nrf2), perhaps ameliorating oxidative stress-induced damage. However, it is not known whether DMF also activates Nrf2 in peripheral immune cells, which are known to participate in CNS demyelination. We conducted a single observation study to determine whether DMF can activate Nrf2 in peripheral immune cells in vitro...
November 2, 2017: BMC Research Notes
Britta Bauer, Anna-Lena Göderz, Heidi Braumüller, Jörg Martin Neudörfl, Martin Röcken, Thomas Wieder, Hans-Günther Schmalz
Autoimmune diseases are characterized by dendritic cell (DC)-driven activation of pro-inflammatory T cell responses. Therapeutic options for these severe diseases comprise small molecules such as dimethyl fumarate, or "gasotransmitters" such as CO. Herein we describe the synthesis of bifunctional enzyme-triggered CO-releasing molecules (ET-CORMs) that allow the simultaneous intracellular release of both CO and methyl fumarate. Using bone-marrow-derived DCs the impressive therapeutic potential of these methyl fumarate-derived compounds (FumET-CORMs) is demonstrated by strong inhibition of lipopolysaccharide-induced pro-inflammatory signaling pathways and blockade of downstream interleukin-12 or -23 production...
November 2, 2017: ChemMedChem
Pramod Kumar, Gajanand Sharma, Rajendra Kumar, Ruchi Malik, Bhupinder Singh, Om Prakash Katare, Kaisar Raza
AIM: Dimethyl fumarate is a frequent prescription for the management of numerous neurological disorders. Despite immense promises, DMF is associated with various problems such as multiple dosing (2-3 oral doses daily) and lower brain permeability. Our aim was to enhance the oral bioavailability and increase the brain concentrations of dimethyl fumarate. METHODS: Solid lipid nanoparticles were systematically formulated by optimizing the composition based on the desired attributes viz...
November 2, 2017: Nanomedicine
Amandine Mathias, Sylvain Perriot, Mathieu Canales, Claudia Blatti, Coline Gaubicher, Myriam Schluep, Britta Engelhardt, Renaud Du Pasquier
OBJECTIVE: To evaluate the long-term effects of treatments used in MS on the T-cell trafficking profile. METHODS: We enrolled 83 patients with MS under fingolimod (FTY), natalizumab (NTZ), dimethyl fumarate (DMF), or other disease-modifying treatments (DMTs). Blood was drawn before treatment onset and up to 36-48 months. The ex vivo expression of CNS-related integrins (α4β1 and αL subunit of LFA-1) and the gut-related integrin (α4β7) was assessed using flow cytometry on CD4(+) and CD8(+) T cells...
November 2017: Neurology® Neuroimmunology & Neuroinflammation
Yuuki Yamaguchi, Hiroyuki Kanzaki, Yuta Katsumata, Kanako Itohiya, Sari Fukaya, Yutaka Miyamoto, Tsuyoshi Narimiya, Satoshi Wada, Yoshiki Nakamura
Bone destructive diseases are common worldwide and are caused by dysregulation of osteoclast formation and activation. During osteoclastogenesis, reactive oxygen species (ROS) play a role in the intracellular signalling triggered by receptor activator of nuclear factor-κB ligand (RANKL) stimulation. Previously, we demonstrated that induction of antioxidant enzymes by Nrf2 activation using Nrf2-gene transfer, an ETGE-peptide or polyphenols, successfully ameliorated RANKL-dependent osteoclastogenesis. Dimethyl fumarate (DMF) has been shown to activate Nrf2 signalling and has been lately used in clinical trials for neurodegenerative diseases...
October 24, 2017: Journal of Cellular and Molecular Medicine
Regina Berkovich
OBJECTIVE: To evaluate clinical and MRI outcomes after stopping or switching disease-modifying therapy in patients with stable MS. METHODS: A retrospective chart review was conducted of stable MS patients who discontinued or switched their DMT from 2011 to 2015. Clinical and MRI outcomes were obtained at baseline and 1-year follow-up. RESULTS: For the DMT discontinuation group, 15 patients were included, with 67% female, 53% Caucasian, mean age of 45...
October 2017: Multiple Sclerosis and related Disorders
Lisa Lindström, Maria Alvarado-Kristensson
Overexpression of γ-tubulin leads to the formation of filaments, but nothing is known about such filaments with regard to possible presence in cells, structure and probable dynamics. Here, we used mammalian cell lines to investigate the ability of γ-tubulin to form filaments. We found that γ-tubulin produces fibers called γ-tubules in a GTP-dependent manner and that γ-tubules are made up of pericentrin and the γ-tubulin complex proteins 2, 3, 5 and 6. Furthermore, we noted that the number of cells with cytosolic γ-tubules is increased in non-dividing cells...
October 16, 2017: Biochimica et Biophysica Acta
Sriram Krishnamoorthy, Betty Pace, Dipti Gupta, Sarah Sturtevant, Biaoru Li, Levi Makala, Julia Brittain, Nancy Moore, Benjamin F Vieira, Timothy Thullen, Ivan Stone, Huo Li, William E Hobbs, David R Light
Sickle cell disease (SCD) results from a point mutation in the β-globin gene forming hemoglobin S (HbS), which polymerizes in deoxygenated erythrocytes, triggering recurrent painful vaso-occlusive crises and chronic hemolytic anemia. Reactivation of fetal Hb (HbF) expression ameliorates these symptoms of SCD. Nuclear factor (erythroid derived-2)-like 2 (Nrf2) is a transcription factor that triggers cytoprotective and antioxidant pathways to limit oxidative damage and inflammation and increases HbF synthesis in CD34+ stem cell-derived erythroid progenitors...
October 19, 2017: JCI Insight
Georgios Tsivgoulis, Georgios N Papadimitropoulos, Aristeidis H Katsanos, Christina Zompola, Apostolos Safouris, Odysseas Kargiotis, Konstantinos Voumvourakis
No abstract text is available yet for this article.
October 10, 2017: Neurology
Michela Campolo, Giovanna Casili, Marika Lanza, Alessia Filippone, Irene Paterniti, Salvatore Cuzzocrea, Emanuela Esposito
Alzheimer disease (AD) is characterized by a complex heterogeneity of pathological changes, and any therapeutic approach categorically requires a multi-targeted way. It has been demonstrated that together with the hallmarks of the disease such as neurofibrillary tangles and senile plaques, oxidative and inflammatory stress covered an important role. Dimethyl fumarate (DMF) is an orally bioavailable methyl ester of fumaric acid and activator of Nrf2 with potential neuroprotective and immunomodulating activities...
October 9, 2017: Journal of Cellular and Molecular Medicine
Johanna Breuer, Sebastian Herich, Tilman Schneider-Hohendorf, Achmet I Chasan, Nina Wettschureck, Catharina C Gross, Karin Loser, Alexander Zarbock, Johannes Roth, Luisa Klotz, Heinz Wiendl, Nicholas Schwab
OBJECTIVE: Dimethyl fumarate (DMF) is prescribed against relapsing-remitting multiple sclerosis (MS). Here, we investigated the effects of DMF and monomethyl fumarate (MMF), its metabolite in vivo, at the (inflamed) blood-brain barrier (BBB). METHODS: Effects of fumaric acid esters were analyzed using primary human brain-derived microvascular endothelial cells (HBMECs) in combination with peripheral blood mononuclear cells (PBMCs) derived from DMF-treated MS patients...
October 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
Sarah E Fiedler, Joshua D George, Haley N Love, Edward Kim, Rebecca Spain, Dennis Bourdette, Sonemany Salinthone
OBJECTIVE AND DESIGN: The etiology of multiple sclerosis (MS) is unknown, but blood derived monocytes/macrophages are believed to be involved in the pathogenesis through phagocytosis of myelin and production of inflammatory mediators. The objective of this study is to examine inflammatory cytokines that are present at elevated levels in active MS lesions to determine whether there are differences between classically stimulated monocytes isolated from healthy control (HC) and relapsing-remitting MS (RRMS) subjects taking disease modifying drugs (DMDs), including dimethyl fumarate (DMF)...
May 2017: Journal of Systems and Integrative Neuroscience
Neda Djedović, Suzana Stanisavljevic, Bojan Jevtić, Miljana Momčilović, Irena Lavrnja, Djordje Miljković
Ethyl pyruvate is a redox analogue of dimethyl fumarate (Tecfidera), a drug for multiple sclerosis treatment. We have recently shown that ethyl pyruvate ameliorates experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. It affects encephalitogenic T cells and macrophages in vitro, as well as in lymph nodes draining the site of encephalitogenic immunization and within the central nervous system (CNS). Here, in vivo effects of ethyl pyruvate on EAE are thoroughly investigated in the CNS and within the gut associated lymphoid tissue...
September 28, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Katy Wright, Mandy D Winkler, Braeden D Newton, Maria Pia Sormani, Darin T Okuda
OBJECTIVE: To examine the temporal profile of absolute and lymphocyte subset data from dimethyl fumarate (DMF) start and relationships to disease behavior. METHODS: A retrospective study performed on patients with an existing diagnosis of MS and a history of DMF exposure from a single MS center. Demographic, laboratory, and corresponding clinical relapse and MRI data were recorded from baseline and in 3-4-month intervals after treatment initiation extending to 3 years...
November 2017: Neurology® Neuroimmunology & Neuroinflammation
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