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Dimethylfumarate

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https://www.readbyqxmd.com/read/29603404/a-review-of-the-mechanisms-of-action-of-dimethylfumarate-dmf-in-the-treatment-of-psoriasis
#1
REVIEW
J Brück, R Dringen, A Amasuno, I Pau-Charles, K Ghoreschi
Fumaric acid esters (FAEs) like dimethylfumarate (DMF) are used for the treatment of adults with moderate to severe psoriasis. The mode of action of FAEs is complex. Here we provide a comprehensive review of the literature to describe the molecular mechanisms by which DMF and its active metabolite monomethylfumarate (MMF) exert their anti-inflammatory and immune modulatory effects. MMF can bind to the hydroxy-carboxylic acid receptor 2 (HCA2) on the cell surface and both DMF and MMF react with intracellular glutathione following cell penetration...
March 30, 2018: Experimental Dermatology
https://www.readbyqxmd.com/read/29526118/first-line-disease-modifying-drugs-in-relapsing-remitting-multiple-sclerosis-an-italian-real-life-multicenter-study-on-persistence
#2
Diana Ferraro, Valentina Camera, Eleonora Baldi, Veria Vacchiano, Erica Curti, Angelica Guareschi, Susanna Malagù, Sara Montepietra, Silvia Strumia, Mario Santangelo, Luisa Caniatti, Matteo Foschi, Alessandra Lugaresi, Franco Granella, Ilaria Pesci, Luisa Motti, Walter Neri, Paolo Immovilli, Enrico Montanari, Francesca Vitetta, Anna Maria Simone, Patrizia Sola
OBJECTIVE: The introduction of oral disease-modifying drugs (DMDs) in addition to the available, injectable, ones for relapsing-remitting multiple sclerosis (RRMS) could be expected to improve medication persistence due to a greater acceptability of the route of administration. The aim of the study was to compare the proportion of patients discontinuing injectable DMDs (interferon beta 1a/1b, pegylated interferon, glatiramer acetate) with those discontinuing oral DMDs (dimethylfumarate and teriflunomide) during an observation period of at least 12 months...
April 12, 2018: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/29500302/oral-therapies-for-multiple-sclerosis
#3
Simon Faissner, Ralf Gold
Multiple sclerosis treatment faces tremendous changes owing to the approval of new medications, some of which are available as oral formulations. Until now, the four orally available medications, fingolimod, dimethylfumarate (BG-12), teriflunomide, and cladribine have received market authorization, whereas laquinimod is still under development. Fingolimod is a sphingosine-1-phosphate inhibitor, which is typically used as escalation therapy and leads to up to 60% reduction of the annualized relapse rate, but might also have neuroprotective properties...
March 2, 2018: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/29478287/altered-epigenetic-pathways-and-cell-cycle-dysregulation-in-healthy-appearing-skin-of-patients-with-koebnerized-squamous-cell-carcinomas-following-skin-surgery
#4
T Gambichler, I Rüddel, S Hessam, F G Bechara, E Stockfleth, L Schmitz
BACKGROUND: Koebnerized non-melanoma skin cancer following skin trauma represents a rare and obscure event. OBJECTIVES: To study molecular pathological parameters in koebnerized squamous cell carcinomas (K-SCCs) occurring after complete tumour removal. METHODS: We assessed two patients with multiple sclerosis who were on treatment with dimethylfumarate (DMF) preceded by long-term azathioprine therapy. Both patients rapidly developed several K-SCCs following histopathologically proven complete excision of cutaneous SCCs...
February 25, 2018: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/29337444/-fumarates-far-more-than-a-dietary-supplement
#5
Wolf-Henning Boehncke, Nicolo Costantino Brembilla
Fumaric acid has an important role in the citric acid cycle. Its esters were first used by a German chemist to treat his own psoriasis, hypothesizing that the disease may be related to disturbances in this very cycle. Meanwhile, the mechanisms underlying its anti-inflammatory efficacy are much better understood. A monosubstance derived from the mix of esters used originally is now being authorized for treating multiple sclerosis, and in 2017 dimethylfumaric acid ester became a globally available option to treat psoriasis...
January 10, 2018: Revue Médicale Suisse
https://www.readbyqxmd.com/read/29183628/the-pharmacokinetics-of-fumaric-acid-esters-reveal-their-in-vivo-effects
#6
REVIEW
Ulrich Mrowietz, Peter John Morrison, Ina Suhrkamp, Margaret Kumanova, Bernd Clement
Fumaric acid ester-based drugs are used for the treatment of psoriasis and multiple sclerosis. All licensed fumaric acid ester drugs contain dimethylfumarate (DMF) as the main active component. Due to the expanding use of oral DMF there is growing scientific interest in determining its as-yet-unknown mechanism of action. However, the pharmacology and chemistry of DMF are often not fully considered in the design and interpretation of experiments; namely, that while DMF is plasma-membrane permeable and has strong effects on many cell types in vitro, it is rapidly metabolized into membrane-impermeable monomethylfumarate (MMF) in vivo...
January 2018: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/28986302/activation-of-nrf2-might-reduce-oxidative-stress-in-human-granulosa-cells
#7
Nana Akino, Osamu Wada-Hiraike, Hiromi Terao, Harunori Honjoh, Wataru Isono, Houju Fu, Mana Hirano, Yuichiro Miyamoto, Michihiro Tanikawa, Miyuki Harada, Tetsuya Hirata, Yasushi Hirota, Kaori Koga, Katsutoshi Oda, Kei Kawana, Tomoyuki Fujii, Yutaka Osuga
Nuclear factor-E2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1)-antioxidant response element (ARE) signaling pathway is one of the most important defense mechanisms against oxidative stress (OS). It is well documented that equilibration status of OS plays fundamental roles in human reproductive medicine, and the physiological role of Nrf2 in ovarian granulosa cells (GCs) has not been determined yet. Herein we aimed to study the function of Nrf2 in GCs. Human ovarian tissues were subjected to immunohistochemistry to localize Nrf2 and Keap1 and we detected the expression of Nrf2 and Keap1 in the human GCs...
October 4, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28732748/controlling-the-pro-inflammatory-function-of-6-sulfo-lacnac-slan-dendritic-cells-with-dimethylfumarate
#8
Stephanie Oehrl, Florina Olaru, Anja Kunze, Michael Maas, Silvia Pezer, Marc Schmitz, Knut Schäkel
BACKROUND: The fumaric acid ester (FAE) dimethylfumarate (DMF) is a small molecule immunomodulator successfully used for the treatment of psoriasis and multiple sclerosis (MS). DMF is thought to inhibit pathogenic immune responses with Th17/Th1T cells, and IL-23/IL-12 producing dendritic cells (DCs). 6-sulfo LacNAc expressing dendritic cells (slanDCs) are a human pro-inflammatory cell type found frequently among the infiltrating leukocytes in skin lesions of psoriasis and brain lesions of MS...
June 24, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28633807/differential-induction-of-atf3-and-ho-1-in-myeloid-cells-and-keratinocytes-via-dimethylfumarate-or-cyclosporine-a
#9
Stefanie Müller, Nikola Smatlik, Marc Burian, Kamran Ghoreschi, Martin Röcken, Amir S Yazdi
BACKGROUND: Chronic inflammatory skin diseases are characterized by controlled proliferation of keratinocytes. Here, activating transcription factor 3 (ATF3) might play a fundamental role. In these inflammatory diseases, proliferation is controlled and only rarely leads to cancer development which can be supported by an inflammatory microenvironment. ATF3 is a dual function protein as it suppresses pro-inflammatory IL-6 and IL-8, but also acts as a pro-oncogenic factor by the suppression of p53...
June 12, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28526975/lipid-nanoparticles-for-administration-of-poorly-water-soluble-neuroactive-drugs
#10
Elisabetta Esposito, Markus Drechsler, Paolo Mariani, Federica Carducci, Michela Servadio, Francesca Melancia, Patrizia Ratano, Patrizia Campolongo, Viviana Trezza, Rita Cortesi, Claudio Nastruzzi
This study describes the potential of solid lipid nanoparticles and nanostructured lipid carriers as nano-formulations to administer to the central nervous system poorly water soluble drugs. Different neuroactive drugs, i.e. dimethylfumarate, retinyl palmitate, progesterone and the endocannabinoid hydrolysis inhibitor URB597 have been studied. Lipid nanoparticles constituted of tristearin or tristearin in association with gliceryl monoolein were produced. The nanoencapsulation strategy allowed to obtain biocompatible and non-toxic vehicles, able to increase the solubility of the considered neuroactive drugs...
September 2017: Biomedical Microdevices
https://www.readbyqxmd.com/read/28486503/depletion-of-saccharomyces-cerevisiae-in-psoriasis-patients-restored-by-dimethylfumarate-therapy-dmf
#11
Hester Eppinga, H Bing Thio, Marco W J Schreurs, Blerdi Blakaj, Ruena I Tahitu, Sergey R Konstantinov, Maikel P Peppelenbosch, Gwenny M Fuhler
BACKGROUND: Psoriasis and inflammatory bowel disease (IBD) are chronic inflammatory diseases sharing similar pathogenic pathways. Intestinal microbial changes such as a decrease of bakers' yeast Saccharomyces cerevisiae have been reported in IBD, suggesting the presence of a gut-skin axis. OBJECTIVE: To investigate whether the S. cerevisiae abundance was altered in psoriasis patients versus healthy controls, and whether dimethylfumarate (DMF) interacted with this yeast...
2017: PloS One
https://www.readbyqxmd.com/read/28322482/progressive-multifocal-leukoencephalopathy-associated-with-fumaric-acid-esters-treatment-in-psoriasis-patients
#12
D M W Balak, E Hajdarbegovic, W M Bramer, H A M Neumann, H B Thio
BACKGROUND: Fumaric acid esters (FAEs) are a systemic treatment for psoriasis considered to have a favourable long-term safety profile without an increased risk for immunosuppression. However, progressive multifocal leukoencephalopathy (PML), a rare, opportunistic viral infection of the central nervous system, has been linked anecdotally to FAE treatment. OBJECTIVE: To assess clinical features and outcomes of FAE-associated PML cases. METHODS: Systematic literature search in multiple databases up to 25th February 2016 for reports of PML in psoriasis patients treated with FAEs...
March 21, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28123399/the-status-of-nrf2-based-therapeutics-current-perspectives-and-future-prospects
#13
REVIEW
Irina G Gazaryan, Bobby Thomas
This mini-review presents the authors' vision on the current status and future trends in the development of neuroprotective agents working via activation of nuclear factor erythroid 2-related factor 2 (Nrf2), and in particular, via disruption of Nrf2-Keap1 interaction. There are two opposite "chemical" mechanisms underlying such activation: the first one is a non-specific covalent modification of Keap1 thiols, resulting in side effects of varied severity, and the second one is the shift of the Nrf2-Kelch-like ECH associated protein-1 (Keap1) binding equilibrium in the presence of a competitive and chemically benign displacement agent...
November 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/27743338/erratum-to-dimethylfumarate-induces-cell-cycle-arrest-and-apoptosis-via-regulating-intracellular-redox-systems-in-hela-cells
#14
Guocan Han, Qiang Zhou
No abstract text is available yet for this article.
December 2016: In Vitro Cellular & Developmental Biology. Animal
https://www.readbyqxmd.com/read/27496192/dimethylfumarate-induces-cell-cycle-arrest-and-apoptosis-via-regulating-intracellular-redox-systems-in-hela-cells
#15
Guocan Han, Qiang Zhou
Dimethylfumarate (DMF) is cytotoxic to several kinds of cells and serves as an anti-tumor drug. This study was designed to investigate the effects and underlying mechanism of DMF on cervical cancer cells. HeLa cells were cultured and treated with 0, 50, 100, 150, and 200 μM DMF, respectively. After 24 h, cell growth was evaluated using Cell Counting Kit-8 (CCK-8) assay and the cell cycle was examined using flow cytometry. In addition, cell apoptosis was detected by Annexin V/propidium iodide (PI) staining and the expressions of caspase-3 and poly-ADP-ribose polymerase (PARP) were detected using western blotting...
December 2016: In Vitro Cellular & Developmental Biology. Animal
https://www.readbyqxmd.com/read/27468725/dimethylfumarate-inhibits-melanoma-cell-proliferation-via-p21-and-p53-induction-and-bcl-2-and-cyclin-b1-downregulation
#16
Irina Kaluzki, Igor Hrgovic, Tsige Hailemariam-Jahn, Monika Doll, Johannes Kleemann, Eva Maria Valesky, Stefan Kippenberger, Roland Kaufmann, Nadja Zoeller, Markus Meissner
Recent evidence suggests that dimethylfumarate (DMF), known as a highly potent anti-psoriatic agent, might have anti-tumorigenic properties in melanoma. It has recently been demonstrated that DMF inhibits melanoma proliferation by apoptosis and cell cycle inhibition and therefore inhibits melanoma metastasis. Nonetheless, the underlying mechanisms remain to be evaluated. To elucidate the effects of DMF on melanoma cell lines (A375, SK-Mel), we first performed cytotoxicity assays. No significant lactatedehydogenase (LDH) release could be found...
October 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/27376248/dimethyl-and-monomethylfumarate-regulate-indoleamine-2-3-dioxygenase-ido-activity-in-human-immune-cells
#17
Sevgi Eminel, Na Jin, Martin Rostami, Stefan Dibbert, Ulrich Mrowietz, Ina Suhrkamp
Fumaric acid esters (FAEs) are used as an oral treatment for psoriasis. Dimethylfumarate (DMF) and its metabolite monomethylfumarate (MMF) are regarded as the pharmacologically active moieties. Indoleamine 2,3-dioxygenase (IDO) is the key enzyme for the metabolism of tryptophan. The kynurenine pathway is established as a major regulator of innate and adaptive immunity. Here, we investigated the effect of DMF and MMF on IDO activity and expression in human peripheral blood mononuclear cells (PBMCs). IDO activity was determined by measuring the concentration of kynurenine in the culture medium using a HPLC technique...
August 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/27312167/immunological-treatment-of-multiple-sclerosis
#18
REVIEW
Martin Diebold, Tobias Derfuss
Treatment of multiple sclerosis (MS) has been a challenge since its first description by Charcot. The advent of immunomodulatory drugs in the mid 1990s brought the first big change in the treatment of MS patients. During the last 10 years there has been an ongoing tremendous evolution of novel treatment options for relapsing-remitting MS. These options include monoclonal antibodies, which inhibit migration of lymphocytes (natalizumab), deplete lymphocytes (alemtuzumab), or block the cytokine receptor interleukin (IL)-2 (daclizumab), teriflunomide that inhibits proliferation of activated lymphocytes, fingolimod that modulates the sphingosine-receptor system, and dimethylfumarate that combines features of immunomodulatory and immunosuppressive drugs...
April 2016: Seminars in Hematology
https://www.readbyqxmd.com/read/27277809/distinct-nrf2-signaling-mechanisms-of-fumaric-acid-esters-and-their-role-in-neuroprotection-against-1-methyl-4-phenyl-1-2-3-6-tetrahydropyridine-induced-experimental-parkinson-s-like-disease
#19
Manuj Ahuja, Navneet Ammal Kaidery, Lichuan Yang, Noel Calingasan, Natalya Smirnova, Arsen Gaisin, Irina N Gaisina, Irina Gazaryan, Dmitry M Hushpulian, Ismail Kaddour-Djebbar, Wendy B Bollag, John C Morgan, Rajiv R Ratan, Anatoly A Starkov, M Flint Beal, Bobby Thomas
UNLABELLED: A promising approach to neurotherapeutics involves activating the nuclear-factor-E2-related factor 2 (Nrf2)/antioxidant response element signaling, which regulates expression of antioxidant, anti-inflammatory, and cytoprotective genes. Tecfidera, a putative Nrf2 activator, is an oral formulation of dimethylfumarate (DMF) used to treat multiple sclerosis. We compared the effects of DMF and its bioactive metabolite monomethylfumarate (MMF) on Nrf2 signaling and their ability to block 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced experimental Parkinson's disease (PD)...
June 8, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27192495/the-keap1-nrf2-are-pathway-as-a-potential-preventive-and-therapeutic-target-an-update
#20
REVIEW
Meng-Chen Lu, Jian-Ai Ji, Zheng-Yu Jiang, Qi-Dong You
The Keap1-Nrf2-ARE ((Kelch-like ECH-Associating protein 1) nuclear factor erythroid 2 related factor 2-antioxidant response element) pathway is one of the most important defense mechanisms against oxidative and/or electrophilic stresses, and it is closely associated with inflammatory diseases, including cancer, neurodegenerative diseases, cardiovascular diseases, and aging. In recent years, progress has been made in strategies aimed at modulating the Keap1-Nrf2-ARE pathway. The Nrf2 activator DMF (Dimethylfumarates) has been approved by the FDA as a new first-line oral drug to treat patients with relapsing forms of multiple sclerosis, while a phase 3 study of another promising candidate, CDDO-Me, was terminated for safety reasons...
September 2016: Medicinal Research Reviews
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