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https://www.readbyqxmd.com/read/29664818/initiation-of-disease-modifying-therapies-in-rheumatoid-arthritis-is-associated-with-changes-in-blood-pressure
#1
Joshua F Baker, Brian Sauer, Chia-Chen Teng, Michael George, Grant W Cannon, Said Ibrahim, Amy Cannella, Bryant R England, Kaleb Michaud, Liron Caplan, Lisa A Davis, James OʼDell, Ted R Mikuls
PURPOSE: This study reports the effect of disease-modifying therapies for rheumatoid arthritis (RA) on systolic and diastolic blood pressure (SBP, DBP) over 6 months and incident hypertension over 3 years in a large administrative database. METHODS: We used administrative Veterans Affairs databases to define unique dispensing episodes of methotrexate, leflunomide, sulfasalazine, hydroxychloroquine, tumor necrosis factor inhibitors, and prednisone among patients with RA...
April 17, 2018: Journal of Clinical Rheumatology: Practical Reports on Rheumatic & Musculoskeletal Diseases
https://www.readbyqxmd.com/read/29660056/pyomyositis-an-unusual-cause-of-hip-pain-in-a-patient-on-certolizumab-pegol-and-leflunomide
#2
Surabhi Wig, Paul S McCabe, Smrita Swamy, Jawad Sultan, Sreekanth Vasireddy
No abstract text is available yet for this article.
April 6, 2018: Rheumatology
https://www.readbyqxmd.com/read/29644482/metabolic-syndrome-and-the-decreased-levels-of-uric-acid-by-leflunomide-favor-redox-imbalance-in-patients-with-rheumatoid-arthritis
#3
Neide Tomimura Costa, Bruna Miglioranza Scavuzzi, Tatiana Mayumi Veiga Iriyoda, Marcell Alysson Batisti Lozovoy, Daniela Frizon Alfieri, Fabiano Aparecido de Medeiros, Marcelo Cândido de Sá, Pâmela Lonardoni Micheletti, Bruno Alexandre Sekiguchi, Edna Maria Vissoci Reiche, Michael Maes, Andréa Name Colado Simão, Isaias Dichi
Oxidative stress plays a role in the pathophysiology of rheumatoid arthritis (RA). The aim of the present study was to verify the influence of metabolic syndrome (MetS) and disease-modifying antirheumatic drugs on nitrosative and oxidative biomarkers in patients with RA. A total of 177 patients with RA and 150 healthy volunteers participated in this study, which measured lipid hydroperoxides, advanced oxidation protein products (AOPP), nitric oxide metabolites (NOx), carbonyl protein, total radical-trapping antioxidant parameter (TRAP), uric acid (UA), and C-reactive protein (CRP)...
April 11, 2018: Clinical and Experimental Medicine
https://www.readbyqxmd.com/read/29618584/leflunomide-increases-hepatic-exposure-to-methotrexate-and-its-metabolite-by-differentially-regulating-mrp2-3-4-transporters-via-ppar-%C3%AE-activation
#4
Le Wang, Leilei Ma, Yunfei Lin, Xing Liu, Ling Xiao, Yiting Zhang, Ye Xu, Hu Zhou, Guoyu Pan
Methotrexate (MTX) is the gold standard drug for the treatment of rheumatoid arthritis (RA), and it is frequently combined with leflunomide (LEF) to enhance its clinical efficacy. However, this combination can exacerbate liver toxicity, and the underlying mechanism has not been clarified. We investigated whether LEF affects the pharmacokinetics of MTX and its primary toxic metabolite, 7-hydroxyl methotrexate (7OH MTX), in mice. LEF significantly increased the plasma concentration (AUC) of MTX and 7OH MTX (2...
April 4, 2018: Molecular Pharmacology
https://www.readbyqxmd.com/read/29608766/life-threatening-reversible-bone-marrow-toxicity-in-a-rheumatoid-arthritis-patient-switched-from-leflunomide-to-infliximab
#5
A Marchesoni, M Arreghini, B Panni, N Battafarano, L Uziel
No abstract text is available yet for this article.
March 28, 2018: Rheumatology
https://www.readbyqxmd.com/read/29547712/flaming-mitochondria-the-anti-inflammatory-drug-leflunomide-boosts-mitofusins
#6
Anna Pellattiero, Luca Scorrano
Despite the significance of mitochondrial dynamics in many diseases, drugs that modulate it are lacking. In this issue of Cell Chemical Biology, Miret-Casals et al. (2018) use a phenotypic high-throughput screen to discover a pro-fusion role for the anti-inflammatory drug Leflunomide, paving the way to screen for mitochondrial pro-fusion drug candidates.
March 15, 2018: Cell Chemical Biology
https://www.readbyqxmd.com/read/29546609/igg4-related-disease-beyond-glucocorticoids
#7
REVIEW
Mitsuhiro Akiyama, Tsutomu Takeuchi
IgG4-related disease is a heterogeneous immune-mediated fibroinflammatory condition that can affect every single organ. This disease is more prevalent in the elderly (the mean age of patients is above 60 years) and the prevalence rate is estimated to be over 4.6 per 100,000 population. Before making a diagnosis, the exclusion of malignancies, lymphoma, anti-neutrophil cytoplasmic antibody-associated vasculitis, multicentric Castleman disease, and other mimickers is crucial for appropriate treatment. Broad management guidelines have been published emphasizing the need for prompt treatment and the use of glucocorticoids as first-line drug therapy for induction of remission...
March 15, 2018: Drugs & Aging
https://www.readbyqxmd.com/read/29540819/inhibition-of-p70-s6-kinase-activity-by-a77-1726-induces-autophagy-and-enhances-the-degradation-of-superoxide-dismutase-1-sod1-protein-aggregates
#8
Jing Sun, Yarong Mu, Yuanyuan Jiang, Ruilong Song, Jianxin Yi, Jingsong Zhou, Jun Sun, Xinan Jiao, Richard A Prinz, Yi Li, Xiulong Xu
Autophagy plays a central role in degrading misfolded proteins such as mutated superoxide dismutase 1 (SOD1), which forms aggregates in motor neurons and is involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). Autophagy is activated when UNC-51-like kinase 1 (ULK1) is phosphorylated at S555 and activated by AMP-activated protein kinase (AMPK). Autophagy is suppressed when ULK1 is phosphorylated at S757 by the mechanistic target of rapamycin (mTOR). Whether p70 S6 kinase 1 (S6K1), a serine/threonine kinase downstream of mTOR, can also regulate autophagy remains uncertain...
March 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29540672/immunosuppressive-effect-of-arsenic-trioxide-on-islet-xenotransplantation-prolongs-xenograft-survival-in-mice
#9
Bin Zhao, Jun-Jie Xia, Lu-Min Wang, Chang Gao, Jia-Li Li, Jia-Yin Liu, Qi-Jun Cheng, Chen Dai, Qi-Lin Ma, Zhong-Quan Qi, Ben-Hua Zhao
The role of arsenic trioxide (As2 O3 ) in inhibiting immune rejection and prolonging islet allograft survival has been identified in islet allotransplantation. This study aims to explore the role of As2 O3 in islet xenotransplantation and the action mechanism. The streptozotocin (STZ) was used in C57BL/6 mice to induce the type 1 diabetes mellitus (T1DM) for xenotransplantation models establishment. Donor islets were isolated by digesting. The flow cytometry (FCM) was used to analyze lymphocyte types. The blood sugar level was detected by using intraperitoneal glucose tolerance test (IPGTT)...
March 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29540538/a77-1726-leflunomide-blocks-and-reverses-cardiac-hypertrophy-and-fibrosis-in-mice
#10
Zhen-Guo Ma, Xin Zhang, Yu-Pei Yuan, Ya-Ge Jin, Ning Li, Chun-Yan Kong, Peng Song, Qi-Zhu Tang
T cell infiltration and the subsequently increased intracardial chronic inflammation play crucial roles in the development of cardiac hypertrophy and heart failure. A77 1726, the active metabolite of leflunomide, has been reported to have powerful anti-inflammatory and T cells-inhibiting properties. However, the effect of A77 1726 on cardiac hypertrophy remains completely unknown. Herein, we found that A77 1726 treatment attenuated pressure overload or angiotensin II-induced cardiac hypertrophy in vivo, as well as agonist-induced hypertrophic response of cardiomyocytes in vitro...
March 14, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29534752/teriflunomide-promotes-oligodendroglial-differentiation-and-myelination
#11
Peter Göttle, Anastasia Manousi, David Kremer, Laura Reiche, Hans-Peter Hartung, Patrick Küry
BACKGROUND: Multiple sclerosis (MS) is a neuroinflammatory autoimmune disease of the central nervous system (CNS) which in most cases initially presents with episodes of transient functional deficits (relapsing-remitting MS; RRMS) and eventually develops into a secondary progressive form (SPMS). Aside from neuroimmunological activities, MS is also characterized by neurodegenerative and regenerative processes. The latter involve the restoration of myelin sheaths-electrically insulating structures which are the primary targets of autoimmune attacks...
March 13, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29517554/effectiveness-and-drug-survival-of-anti-tumor-necrosis-factor-%C3%AE-therapies-in-patients-with-spondyloarthritis-analysis-from-the-thai-rheumatic-disease-prior-authorization-registry
#12
Praveena Chiowchanwisawakit, Wanruchada Katchamart, Manathip Osiri, Pongthorn Narongroeknawin, Parawee Chevaisrakul, Tasanee Kitumnuaypong, Boonjing Siripaitoon, Worawit Louthrenoo
OBJECTIVE: This study aimed to evaluate the long-term effectiveness and safety of the first anti-tumor necrosis factor α therapy (TNFi) and to identify the associated factors of drug discontinuation in patients with spondyloarthritis. METHODS: This was a retrospective cohort study. Patients with spondyloarthritis who were prescribed the first TNFi between December 2009 and October 2014 in the Rheumatic Disease Prior Authorization registry were enrolled. Baseline clinical data were retrieved...
March 7, 2018: Journal of Clinical Rheumatology: Practical Reports on Rheumatic & Musculoskeletal Diseases
https://www.readbyqxmd.com/read/29508628/drug-associated-pulmonary-arterial-hypertension
#13
Michael McGee, Nicholas Whitehead, Jennifer Martin, Nicholas Collins
INTRODUCTION: While pulmonary arterial hypertension remains an uncommon diagnosis, various therapeutic agents are recognized as important associations. These agents are typically categorized into "definite", "likely", "possible", or "unlikely" to cause pulmonary arterial hypertension, based on the strength of evidence. OBJECTIVE: This review will focus on those therapeutic agents where there is sufficient literature to adequately comment on the role of the agent in the pathogenesis of pulmonary arterial hypertension...
March 6, 2018: Clinical Toxicology
https://www.readbyqxmd.com/read/29505325/safety-of-treatment-options-for-spondyloarthritis-a-narrative-review
#14
Salvatore D'Angelo, Antonio Carriero, Michele Gilio, Francesco Ursini, Pietro Leccese, Carlo Palazzi
Spondyloarthritis (SpA) are chronic inflammatory diseases with overlapping pathogenic mechanisms and clinical features. Treatment armamentarium against SpA includes non-steroidal anti-inflammatory drugs, glucocorticoids, conventional disease-modifying antirheumatic drugs (DMARDs, including sulfasalazine, methotrexate, leflunomide, cyclosporine), targeted synthetic DMARDs (apremilast) and biological DMARDs (TNF inhibitors, anti-IL 12/23 and anti-IL-17 agents). Areas covered: A narrative review of published literature on safety profile of available SpA treatment options was performed...
March 14, 2018: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/29500302/oral-therapies-for-multiple-sclerosis
#15
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/29496905/control-of-hyperglycemia-in-male-mice-by-leflunomide-mechanisms-of-action
#16
Junhong Chen, Jing Sun, Michelle E Doscas, Jin Ye, Ashley J Williamson, Yanchun Li, Yi Li, Richard A Prinz, Xiulong Xu
p70 S6 kinase (S6K1) is a serine/threonine kinase that phosphorylates the insulin receptor substrate-1 (IRS-1) at serine 1101 and desensitizes insulin receptor signaling. S6K1 hyperactivation due to overnutrition leads to hyperglycemia and type 2 diabetes. Our recent study showed that A77 1726, the active metabolite of the anti-rheumatoid arthritis (RA) drug leflunomide, is an inhibitor of S6K1. Whether leflunomide can control hyperglycemia and sensitize the insulin receptor has not been tested. Here we report that A77 1726 increased AKTS473/T308 and S6K1T389 phosphorylation but decreased S6S235/236 and IRS-1S1101 phosphorylation in 3T3-L1 adipocytes, C2C12 and L6 myotubes...
April 2018: Journal of Endocrinology
https://www.readbyqxmd.com/read/29481912/suppression-of-aberrant-choroidal-neovascularization-through-activation-of-the-aryl-hydrocarbon-receptor
#17
Mayur Choudhary, Stephen Safe, Goldis Malek
The aryl hydrocarbon receptor (AhR) is a ligand activated transcription factor, initially discovered for its role in regulating xenobiotic metabolism. There is extensive evidence supporting a multi-faceted role for AhR, modulating physiological pathways important in cell health and disease. Recently we demonstrated that the AhR plays a role in the pathogenesis of age-related macular degeneration (AMD), the leading cause of vision loss in the elderly. We found that loss of AhR exacerbates choroidal neovascular (CNV) lesion formation in a murine model...
February 23, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29473796/severe-hypertriglyceridemia-associated-with-teriflunomide-in-a-patient-with-multiple-sclerosis-a-case-report
#18
Carlos R Camara-Lemarroy, Joaquín Castilló, Jaume Sastre-Garriga, Mar Tintore, Xavier Montalban
OBJECTIVE: To describe a case of severe hypertriglyceridemia in a patient receiving teriflunomide. METHODS: This is a case study. RESULTS: Our patient developed severe hypertriglyceridemia (>5000 mg/dL) while on teriflunomide. The drug was withdrawn. Resolution began over 3 weeks later. CONCLUSION: We describe the first probable case of teriflunomide-associated severe hypertriglyceridemia in a patient with multiple sclerosis, an adverse event previously associated with leflunomide in patients with rheumatologic diseases...
February 1, 2018: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/29427785/mitochondrial-dysfunction-induced-by-leflunomide-and-its-active-metabolite
#19
Jiekun Xuan, Zhen Ren, Tao Qing, Letha Couch, Leming Shi, William H Tolleson, Lei Guo
Leflunomide, an anti-inflammatory drug used for the treatment of rheumatoid arthritis, has been marked with a black box warning regarding an increased risk of liver injury. The active metabolite of leflunomide, A771726, which also carries a boxed warning about potential hepatotoxicity, has been marketed as teriflunomide for the treatment of relapsing multiple sclerosis. Thus far, however, the mechanism of liver injury associated with the two drugs has remained elusive. In this study, cytotoxicity assays showed that ATP depletion and subsequent LDH release were induced in a time- and concentration-dependent manner by leflunomide in HepG2 cells, and to a lesser extent, by A77 1726...
February 7, 2018: Toxicology
https://www.readbyqxmd.com/read/29423085/the-anti-rheumatic-drug-leflunomide-synergizes-with-mek-inhibition-to-suppress-melanoma-growth
#20
Kimberley Hanson, Stephen R Robinson, Karamallah Al-Yousuf, Adam E Hendry, Darren W Sexton, Victoria Sherwood, Grant N Wheeler
Cutaneous melanoma, which develops from the pigment producing cells called melanocytes, is the most deadly form of skin cancer. Unlike the majority of other cancers, the incidence rates of melanoma are still on the rise and the treatment options currently available are being hindered by resistance, limited response rates and adverse toxicity. We have previously shown that an FDA approved drug leflunomide, used for rheumatoid arthritis (RA), also holds potential therapeutic value in treating melanoma especially if used in combination with the mutant BRAF inhibitor, vemurafenib...
January 9, 2018: Oncotarget
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