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Leflunomide

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https://www.readbyqxmd.com/read/29042208/antiallodynic-activity-of-leflunomide-is-partially-inhibited-by-naltrexone-and-glibenclamide-and-associated-with-reduced-production-of-tnf-%C3%AE-and-cxcl-1
#1
Ana Mercy S Brito, Adriana M Godin, Paulo Sérgio A Augusto, Raquel R Menezes, Ivo S F Melo, Marcela G M B Dutra, Sarah O A M Costa, Franciele A Goulart, Felipe F Rodrigues, Isis MoraisMarcela Ísis Morais, Renes R Machado, Márcio M Coelho
Leflunomide, an immunosuppressive drug approved for the treatment of patients with rheumatoid arthritis, exhibits many mechanisms which may affect the nociceptive processing. Therefore, the present study aimed to evaluate the effect induced by leflunomide on the mechanical allodynia in models of inflammatory and neuropathic pain in mice and investigate mechanisms mediating such effects. Per os (p.o.) administration of leflunomide (25, 50 or 100 mg/kg) inhibited the inflammatory edema and mechanical allodynia induced by intraplantar carrageenan...
October 14, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29039518/leflunomide-inhibits-proliferation-and-tumorigenesis-of-oral-squamous-cell-carcinoma
#2
Aishu Ren, Gang Fu, Yu Qiu, Hongjuan Cui
Oral squamous cell carcinoma (OSCC) is the most prevalent pathological cancer occurring in the head and neck area. Progress has previously been made regarding treatment strategies of OSCC, however the 5‑year survival rate of these patients is only 50%. The present study examined if leflunomide (LEF), a drug primarily used for the treatment of rheumatoid arthritis, exhibited antitumor effects in OSCC. The results demonstrated that LEF inhibited cell proliferation and blocked the cell cycle at the S phase in OSCC cells, with upregulation of cyclin A protein expression...
October 10, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29038464/unveiling-some-fda-approved-drugs-as-inhibitors-of-the-store-operated-ca-2-entry-pathway
#3
Saifur Rahman, Taufiq Rahman
The store-operated calcium entry (SOCE) pathway is an important route for generating cytosolic Ca(2+) signals that regulate a diverse array of biological processes. Abnormal SOCE seem to underlie several diseases that notably include allergy, inflammation and cancer. Therefore, any modulator of this pathway is likely to have significant impact in cell biology under both normal and abnormal conditions. In this study, we screened the FDA-approved drug library for agents that share significant similarity in 3D shape and surface electrostatics with few, hitherto best known inhibitors of SOCE...
October 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29037899/the-management-of-first-line-biologic-therapy-failures-in-rheumatoid-arthritis-current-practice-and-future-perspectives
#4
REVIEW
Ennio Giulio Favalli, Maria Gabriella Raimondo, Andrea Becciolini, Chiara Crotti, Martina Biggioggero, Roberto Caporali
The introduction of biologic disease-modifying anti-rheumatic drugs (bDMARDs) has dramatically changed the management of rheumatoid arthritis (RA). However, in a real-life setting about 30-40%. of bDMARD treated patients experience drug discontinuation because of either inefficacy or adverse events. According to international recommendations, to date the best strategy for managing first-line bDMARD failures has not been defined yet and available data (especially on TNF inhibitors [TNFis]) seem to drive toward a personalized approach for the individual patient...
October 13, 2017: Autoimmunity Reviews
https://www.readbyqxmd.com/read/29037312/rheumatoid-arthritis-seems-to-have-dmard-treatment-decision-influenced-by-fibromyalgia
#5
Rafael Mendonça da Silva Chakr, Claiton Brenol, Aline Ranzolin, Amanda Bernardes, Ana Paula Dalosto, Giovani Ferrari, Stephanie Scalco, Vanessa Olszewski, Charles Kohem, Odirlei Monticielo, João Carlos T Brenol, Ricardo M Xavier
OBJECTIVE: To compare DMARD use in patients with and without FM over time, including overtreatment and undertreatment rates in both groups. METHODS: A prospective cohort study with patients attending an RA outpatient clinic was conducted. Participants were consecutively recruited between March 2006 and June 2007 and were followed through December 2013. Data on DMARD use (prevalences, doses and escalation rates), DAS28, HAQ and radiographic progression were compared among RA patients with FM and without FM...
September 2017: Revista Brasileira de Reumatologia
https://www.readbyqxmd.com/read/29033202/-pyopneumothorax-in-rheumatoid-arthritis
#6
B Huret, S Boulanger, L Benhamed, X Deprez, D Caparros
INTRODUCTION: Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting the joints but which frequently includes extra articular effects, including pulmonary nodules, which grow faster under immunosuppressive treatment. CASE REPORT: A 74 years old man, with mild asbestosis, underwent treatment with methotrexate then leflunomide (LEF) for seropositive RA. In February 2014, during monitoring of his asbestosis, chest CT scan showed the appearance of thick-walled cavitating lung nodules, with a central and sub pleural distribution...
October 12, 2017: Revue des Maladies Respiratoires
https://www.readbyqxmd.com/read/28988120/endoplasmic-reticulum-stress-and-mapk-signaling-pathway-activation-underlie-leflunomide-induced-toxicity-in-hepg2-cells
#7
Zhen Ren, Si Chen, Tao Qing, Jiekun Xuan, Letha Couch, Dianke Yu, Baitang Ning, Leming Shi, Lei Guo
Leflunomide, used for the treatment of rheumatoid arthritis, has been reported to cause severe liver problems and liver failure; however, the underlying mechanisms are not clear. In this study, we used multiple approaches including genomic analysis to investigate and characterize the possible molecular mechanisms of the cytotoxicity of leflunomide in hepatic cells. We found that leflunomide caused endoplasmic reticulum (ER) stress and activated an unfolded protein response, as evidenced by increased expression of related genes including CHOP and GADD34; and elevated protein levels of typical ER stress markers including CHOP, ATF-4, p-eIF2α, and spliced XBP1...
October 5, 2017: Toxicology
https://www.readbyqxmd.com/read/28969447/beneficial-effects-of-a-probiotic-blend-on-gastrointestinal-side-effects-induced-by-leflunomide-and-amlodipine-in-a-rat-model
#8
S-C Song, Y-M An, J-H Shin, M-J Chung, J-G Seo, E Kim
Patients with metabolic disorders frequently suffer from side effects induced by long-term oral medications. The present study using a rat model system indicated that leflunomide (LF) and amlodipine (AMD), the active ingredients contained in the medications for rheumatoid arthritis and hypertension, respectively, appeared to induce various bowel problems including constipation and inflammation. In the small and large intestine, LF increased the expression of tumour necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 compared to the null control and AMD increased the expression of both TNF-α and IL-1β, although its effect on IL-6 was only increased in the large intestine...
October 3, 2017: Beneficial Microbes
https://www.readbyqxmd.com/read/28967035/comparative-efficacy-and-tolerability-of-monotherapy-with-leflunomide-or-tacrolimus-for-the-treatment-of-rheumatoid-arthritis-a-bayesian-network-meta-analysis-of-randomized-controlled-trials
#9
Sang-Cheol Bae, Young Ho Lee
We aimed to assess the relative efficacy and tolerability of monotherapy with leflunomide or tacrolimus at recommended dosages in rheumatoid arthritis (RA) patients. Randomized controlled trials (RCTs) examining the efficacy and tolerability of leflunomide 20 mg, leflunomide 10 mg, tacrolimus 3 mg, tacrolimus 1.5-2 mg, and placebo, based on the number of withdrawals of RA patients, were included. We performed a Bayesian random-effects network meta-analysis to combine direct and indirect evidence from the RCTs...
October 1, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28957557/risk-factors-of-serious-infections-in-patients-with-rheumatoid-arthritis-treated-with-tocilizumab-in-the-french-registry-regate
#10
Jacques Morel, Arnaud Constantin, Gabriel Baron, Emmanuelle Dernis, René Marc Flipo, Stéphanie Rist, Bernard Combe, Jacques Eric Gottenberg, Thierry Schaeverbeke, Martin Soubrier, Olivier Vittecoq, Maxime Dougados, Alain Saraux, Xavier Mariette, Philippe Ravaud, Jean Sibilia
Objectives: Observational studies have already reported the risk of serious infections in RA treated with tocilizumab, but in limited samples. The aim of this study was to investigate the predictive risk factors for serious infections in the largest European registry of patients treated with tocilizumab for RA. Methods: A total of 1491 RA patients included in the French REGistry-RoAcTEmra were analysed to calculate the incidence rate of first serious infections rate after initiation of tocilizumab...
October 1, 2017: Rheumatology
https://www.readbyqxmd.com/read/28944992/ginsenoside-rb1-enhances-atherosclerotic-plaque-stability-by-skewing-macrophages-to-the-m2-phenotype
#11
Xue Zhang, Ming-Hao Liu, Lei Qiao, Xin-Yu Zhang, Xiao-Ling Liu, Mei Dong, Hong-Yan Dai, Mei Ni, Xiao-Rong Luan, Jun Guan, Hui-Xia Lu
Atherosclerosis (AS) is characterized as progressive arterial plaque, which is easy to rupture under low stability. Macrophage polarization and inflammation response plays an important role in regulating plaque stability. Ginsenoside Rb1 (Rb1), one of the main active principles of Panax Ginseng, has been found powerful potential in alleviating inflammatory response. However, whether Rb1 could exert protective effects on AS plaque stability remains unclear. This study investigated the role of Rb1 on macrophage polarization and atherosclerotic plaque stability using primary peritoneal macrophages isolated from C57BL/6 mice and AS model in ApoE(-/-) mice...
September 25, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28913596/-perioperative-management-of-immunosuppressive-treatment-in-patients-undergoing-joint-surgery
#12
K Krüger
The perioperative management of patients on immunosuppressive drugs is uncertain due to a lack of controlled studies. Continuation of medication without a pause may increase the risk of postoperative infections and wound healing disorders and when the pause is too long this can induce a flare of the underlying rheumatic disease. Additional factors, such as rheumatic disease activity, comorbidities, previous infections and the type of surgical procedure also modulate the risk. The highest risk of infection is associated with corticosteroids depending on the dose, so that a dosage as low as possible but stable in the perioperative period is recommended...
September 14, 2017: Zeitschrift Für Rheumatologie
https://www.readbyqxmd.com/read/28867467/systematic-review-and-meta-analysis-of-the-efficacy-and-safety-of-leflunomide-and-methotrexate-in-the-treatment-of-rheumatoid-arthritis
#13
Roberto Alfaro-Lara, Hector Fabricio Espinosa-Ortega, César Alejandro Arce-Salinas
OBJECTIVE: To assess the efficacy and side effects of methotrexate and leflunomide in patients with rheumatoid arthritis (RA) as the first disease-modifying antirheumatic drug (DMARD). METHODS: We performed a systematic review and meta-analysis of clinical studies that included patients who took methotrexate, leflunomide, placebo or another DMARD for RA treatment. A systematic review yielded 1971 articles from databases; once completely reviewed, 73 trials that completed inclusion criteria were selected...
August 31, 2017: Reumatología Clinica
https://www.readbyqxmd.com/read/28838440/ganciclovir-dosing-strategies-and-development-of-cytomegalovirus-resistance-in-a-kidney-transplant-recipient-a-case-report
#14
I A Echenique, D Beltran, L Ramirez-Ruiz, N Najafian, N Agrawal
In renal transplant recipients, delayed graft function and accompanying renal impairment may lead to therapeutic underexposure of valganciclovir. We describe a case of a cytomegalovirus (CMV)-seronegative kidney transplant recipient from a CMV-seropositive donor, whose course was complicated during valganciclovir prophylaxis by CMV disease, ultimately progressing to ganciclovir, foscarnet, and cidofovir resistance. Assessments and adjustments for renal dysfunction, according to both Cockgroft-Gault and Modification of Diet in Renal Disease study equations, are described...
September 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28833582/a-retrospective-study-on-the-safety-and-efficacy-of-leflunomide-in-dogs
#15
M Sato, J K Veir, M Legare, M R Lappin
BACKGROUND: Little clinical information is available concerning the use of leflunomide in dogs with immune-mediated diseases. OBJECTIVES: To report the safety and efficacy of leflunomide for the treatment of naturally occurring immune-mediated diseases in dogs. ANIMALS: Ninety-two dogs treated with leflunomide for management of suspected immune-mediated diseases. METHODS: Retrospective medical record review from Jan 1995 to Dec 2014...
September 2017: Journal of Veterinary Internal Medicine
https://www.readbyqxmd.com/read/28774475/what-is-new-in-management-of-takayasu-arteritis
#16
Gokhan Keser, Kenan Aksu
Management of Takayasu arteritis (TAK) is challenging mostly due to difficulties in assessing actual disease activity. The rational of medical treatment is to suppress both vascular and systemic inflammation with appropriate systemic immunosuppression, including corticosteroids and conventional immunosuppressive (IS) agents. In case of refractory disease activity, biologic agents such as TNF inhibitors and tocilizumab may be tried. In selected cases, endovascular interventions and surgical procedures may be indicated and should be performed during inactive disease...
July 2017: La Presse Médicale
https://www.readbyqxmd.com/read/28752968/-effects-of-triptolide-on-the-autophagy-in-synovial-spleen-and-thymus-of-rats-with-adjuvant-arthritis
#17
Lei Wan, Jian Liu, Chuan-Bing Huang, Xiao-Jun Zhang, Ya-Li Wang, Ping-Heng Zhang, Yue Sun, Lei Liu
OBJECTIVE: To determine the effect of triptolide (TP) on the expression of ATG /LC3-Ⅱ Beclin1 in synovial, spleen, and thymusof rats with adjuvant arthritis (AA). METHODS: Rats were divided for four groups: normal control (NC), model control (MC), leflunomide (LEF) treatment, and triptolide (TP)treatment, with 12 rats in each group.The AA model was established through Freund's complete adjuvant (0.1 mL each) injection into the right foot plantar skin to introduce inflammation and 10 days of tail root injection of 0...
July 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28743837/inactivation-deficiency-of-dhodh-induces-cell-cycle-arrest-and-programed-cell-death-in-melanoma
#18
Lichao Liu, Zhen Dong, Qian Lei, Jie Yang, Huanrong Hu, Qian Li, Yacong Ji, Leiyang Guo, Yanli Zhang, Yaling Liu, Hongjuan Cui
Malignant melanoma (MM) is one of the most malignant tumors and has a very poor prognosis. However, there are no effective drugs to treat this disease. As a kind of iron flavin dependent enzyme, dihydroorotate dehydrogenase (DHODH, EC 1.3.3.1) is the fourth and a key enzyme in the de novo biosynthesis of pyrimidines. Herein, we found that DHODH inactivation/deficiency inhibited melanoma cell proliferation, induced cell cycle arrest at S phase and lead to autophagy in human melanoma cells. Meanwhile, leflunomide treatment induced cell apoptosis and deficiency of DHODH sensitized cells to drug-induced apoptosis in BCL-2 deficient melanoma cells, while not in BCL-2 abundant melanoma cells...
July 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28736027/suppression-of-delayed-xenograft-rejection-by-resveratrol-in-a-hamster-to-rat-cardiac-transplantation-model
#19
Y Lian, C Gao, Y Wu, J Xia, Y Leng, Y Liu, M Zhu, J Chen, Z Qi
BACKGROUND: Delayed xenograft rejection (DXR) is an insurmountable barrier for xenotransplantation. Previous studies reported that hamster hearts transplanted into rats undergo DXR and stop functioning after the cessation of immunosuppression. Herein, we investigated the effects of resveratrol on preventing DXR in a hamster-to-rat vascularized cardiac xenograft model. METHODS: Hamster hearts were engrafted into Lewis rat recipients. Recipient rats received a graft acceptance-inducing treatment of leflunomide and FK506 for 2 weeks to prevent acute xenograft rejection (AXR)...
July 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28724365/leflunomide-is-equally-efficacious-and-safe-compared-to-low-dose-rituximab-in-refractory-rheumatoid-arthritis-given-in-combination-with-methotrexate-results-from-a-randomized-double-blind-controlled-clinical-trial
#20
Harindu Wijesinghe, Priyadharshini Galappatthy, Rajiva de Silva, Suranjith L Seneviratne, Ushagowry Saravanamuttu, Preethi Udagama, Melanie Hart, Peter Kelleher, Upul Senerath, Rohini Fernandopulle, Lilani P Weerasekera, Lalith S Wijayaratne
BACKGROUND: The standard dose of rituximab used in rheumatoid arthritis (RA) is 1000 mg but recent studies have shown that low dose (500 mg) is also effective. Efficacy of low dose rituximab in rheumatoid arthritis (RA) refractory to first-line non-biologic Disease Modifying Anti Rheumatic Drugs (DMARDs), compared to leflunomide is unknown. In a tertiary care referral setting, we conducted a randomized, double blind controlled clinical trial comparing the efficacy and safety of low-dose rituximab-methotrexate combination with leflunomide-methotrexate combination...
July 19, 2017: BMC Musculoskeletal Disorders
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