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Macrophage methotrexate

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https://www.readbyqxmd.com/read/29681783/imaging-and-methotrexate-response-monitoring-of-systemic-inflammation-in-arthritic-rats-employing-the-macrophage-pet-tracer-18-f-fluoro-peg-folate
#1
Durga M S H Chandrupatla, Gerrit Jansen, Elise Mantel, Philip S Low, Takami Matsuyama, René P Musters, Albert D Windhorst, Adriaan A Lammertsma, Carla F M Molthoff, Conny J van der Laken
Background: In rheumatoid arthritis, articular inflammation is a hallmark of disease, while the involvement of extra-articular tissues is less well defined. Here, we examined the feasibility of PET imaging with the macrophage tracer [18 F]fluoro-PEG-folate, targeting folate receptor β (FR β ), to monitor systemic inflammatory disease in liver and spleen of arthritic rats before and after methotrexate (MTX) treatment. Methods: [18 F]Fluoro-PEG-folate PET scans (60 min) were acquired in saline- and MTX-treated (1 mg/kg, 4x) arthritic rats, followed by tissue resection and radiotracer distribution analysis...
2018: Contrast Media & Molecular Imaging
https://www.readbyqxmd.com/read/29546609/igg4-related-disease-beyond-glucocorticoids
#2
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/29542334/bayesian-comparative-effectiveness-study-of-four-consensus-treatment-plans-for-initial-management-of-systemic-juvenile-idiopathic-arthritis-first-line-options-for-systemic-juvenile-idiopathic-arthritis-treatment-frost
#3
Peter A Nigrovic, Timothy Beukelman, George Tomlinson, Brian M Feldman, Laura E Schanberg, Yukiko Kimura
BACKGROUND: Systemic juvenile idiopathic arthritis is a rare febrile arthritis of childhood characterized by a potentially severe course, including prolonged glucocorticoid exposure, growth failure, destructive arthritis, and life-threatening macrophage activation syndrome. Early cytokine-blocking biologic therapy may improve long-term outcomes, although some systemic juvenile idiopathic arthritis patients respond well to non-biologic treatment, leaving optimal management undefined. Consequently, treatment of new-onset systemic juvenile idiopathic arthritis by expert clinicians varies widely...
March 1, 2018: Clinical Trials: Journal of the Society for Clinical Trials
https://www.readbyqxmd.com/read/29490676/pharmacological-characterisation-of-cr6086-a-potent-prostaglandin-e-2-receptor-4-antagonist-as-a-new-potential-disease-modifying-anti-rheumatic-drug
#4
Gianfranco Caselli, Albino Bonazzi, Marco Lanza, Flora Ferrari, Daniele Maggioni, Cristian Ferioli, Roberto Giambelli, Eleonora Comi, Silvia Zerbi, Marco Perrella, Ornella Letari, Elena Di Luccio, Milena Colovic, Stefano Persiani, Tiziano Zanelli, Laura Mennuni, Tiziana Piepoli, Lucio Claudio Rovati
BACKGROUND: Prostaglandin E2 (PGE2 ) acts via its EP4 receptor as a cytokine amplifier (e.g., interleukin [IL]-6) and induces the differentiation and expansion of inflammatory T-helper (Th) lymphocytes. These mechanisms play a key role in the onset and progression of rheumatoid arthritis (RA). We present the pharmacological characterisation of CR6086, a novel EP4 receptor antagonist, and provide evidence for its potential as a disease-modifying anti-rheumatic drug (DMARD). METHODS: CR6086 affinity and pharmacodynamics were studied in EP4-expressing HEK293 cells by radioligand binding and cyclic adenosine monophosphate (cAMP) production, respectively...
March 1, 2018: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/29431121/methotrexate-limits-inflammation-through-an-a20-dependent-cross-tolerance-mechanism
#5
Cristina Municio, Ángeles Dominguez-Soto, Sara Fuentelsaz-Romero, Amalia Lamana, Nuria Montes, Víctor D Cuevas, Raquel García Campos, José L Pablos, Isidoro González-Álvaro, Amaya Puig-Kröger
OBJECTIVES: Methotrexate (MTX) is the anchor drug for treatment of rheumatoid arthritis (RA), but the mechanism of its anti-inflammatory action is not fully understood. In RA, macrophages display a proinflammatory polarisation profile that resembles granulocyte-macrophage colony-stimulating factor (GM-CSF)-differentiated macrophages and the response to MTX is only observed in thymidylate synthase+ GM-CSF-dependent macrophages. To determine the molecular basis for the MTX anti-inflammatory action, we explored toll-like receptor (TLR), RA synovial fluid (RASF) and tumour necrosis factor receptor (TNFR)-initiated signalling in MTX-exposed GM-CSF-primed macrophages...
February 3, 2018: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/29407968/aryl-thiosemicarbazones-for-the-treatment-of-trypanosomatidic-infections
#6
Pasquale Linciano, Carolina B Moraes, Laura M Alcantara, Caio H Franco, Bruno Pascoalino, Lucio H Freitas-Junior, Sara Macedo, Nuno Santarem, Anabela Cordeiro-da-Silva, Sheraz Gul, Gesa Witt, Maria Kuzikov, Bernhard Ellinger, Stefania Ferrari, Rosaria Luciani, Antonio Quotadamo, Luca Costantino, Maria Paola Costi
Basing on a library of thiadiazole derivatives showing anti-trypanosomatidic activity, we have considered the thiadiazoles opened forms and reaction intermediates, thiosemicarbazones, as compounds of interest for phenotypic screening against Trypanosoma brucei (Tb), intracellular amastigote form of Leishmania infantum (Li) and Trypanosoma cruzi (Tc). Similar compounds have already shown interesting activity against the same organisms. The compounds were particularly effective against T. brucei and T. cruzi...
January 30, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29361199/mavrilimumab-a-fully-human-granulocyte-macrophage-colony-stimulating-factor-receptor-%C3%AE-monoclonal-antibody-long-term-safety-and-efficacy-in-patients-with-rheumatoid-arthritis
#7
Gerd R Burmester, Iain B McInnes, Joel M Kremer, Pedro Miranda, Jiří Vencovský, Alex Godwood, Marius Albulescu, M Alex Michaels, Xiang Guo, David Close, Michael Weinblatt
OBJECTIVE: Mavrilimumab, a human monoclonal antibody, targets granulocyte-macrophage colony-stimulating factor receptor α. We undertook to determine the long-term safety and efficacy of mavrilimumab in rheumatoid arthritis patients in 2 phase IIb studies (1071 and 1107) and in 1 open-label extension study (ClinicalTrials.gov identifier: NCT01712399). METHODS: In study 1071, patients with an inadequate response to disease-modifying antirheumatic drugs (DMARDs) received mavrilimumab (30, 100, or 150 mg) or placebo every other week plus methotrexate...
January 23, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29273180/-multiple-facets-of-ada2-deficiency-vasculitis-auto-inflammatory-disease-and-immunodeficiency-a-literature-review-of-135-cases-from-literature
#8
A Fayand, G Sarrabay, A Belot, V Hentgen, I Kone-Paut, G Grateau, I Melki, S Georgin-Lavialle
Deficiency of adenosine deaminase 2 (DADA2) is a recently described auto-inflammatory disorder. It is an autosomal recessive inherited disease, caused by mutations in the ADA2 gene (formerly known as CECR1) encoding ADA2 enzyme. Besides its role in the purine metabolism, it has been postulated that ADA2 may act as a growth factor for endothelial cells and in the differenciation of monocytes. Thus, deficiency of ADA2 would lead to endothelial damage and a skewing of monocytes into M1 pro-inflammatory macrophage, causing DADA2 manifestations...
April 2018: La Revue de Médecine Interne
https://www.readbyqxmd.com/read/29228558/1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol-ameliorates-arthritic-joints-through-reducing-neutrophil-infiltration-mediated-by-il-6-stat3-and-mip-2-activation
#9
Young-Jun Kim, Jae Min Shin, Su-Hyun Shin, Joo Heon Kim, Ki-Young Sohn, Heung-Jae Kim, Jong-Koo Kang, Sun Young Yoon, Jae Wha Kim
The pathogenesis of rheumatoid arthritis (RA) has been implicated neutrophil extracellular traps (NETs) formation which could generate autoantigen. Neutrophil contributes to initiate and maintain the inflammatory process in the joint. In this study, we show that 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) decreases neutrophil migration by regulating the activity of STAT3, a regulator of IL-6 and MIP-2 expression. PLAG caused a decrease in IL-6 production in the RAW264.7 macrophage cell line and in rheumatoid arthritis-fibroblast-like synoviocytes via the regulation of STAT3 signaling without affecting NF-κB signaling...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29166574/altered-tnf-%C3%AE-response-by-aconibal%C3%A2-and-methotrexate-in-a-lipopolysaccharide-induced-setting-of-inflammatory-conditions-potential-on-a-synergistic-combination
#10
Gunhyuk Park, Seung Hoon Lee, Ji-Ye Han, Dal-Seok Oh
ETHNOPHARMACOLOGICAL RELEVANCE: Aconitum carmichaelii (AC) is a common herbal medicine used as anti-inflammatory and analgesic agent in Eastern Asia. In Korea, a commercial processed AC (Aconibal®) is traditionally used to treat the symptoms of spondylosis deformans and rheumatic pain. AIM OF STUDY: Rheumatoid arthritis (RA) is systemic and autoimmune disease characterized by chronic inflammation. Methotrexate (MTX) is often the first-line therapy for RA. If MTX monotherapy is ineffective or RA is initially severe, adding a tumor necrosis factor alpha (TNF-α) inhibitor to the treatment can be beneficial...
March 1, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29154446/transmission-electron-microscopy-helpfulness-in-whipple-s-disease-masked-by-immunosuppressant-therapy-for-arthritis
#11
Alessandra Loiodice, Giuseppe Losurdo, Andrea Iannone, Roberta Rossi, Maria Grazia Fiore, Domenico Piscitelli
A 61-year-old woman received a diagnosis of undifferentiated non-erosive arthritis in 2010 and assumed methotrexate and steroids in 2014. After 1 year, she experienced watery diarrhea, vomiting, fever, weight loss, and severe hypoalbuminemia, thus being admitted into our Unit. Esophagogastroduodenoscopy showed duodenal lymphangiectasia and duodenal biopsy samples several foamy PAS-positive macrophages and villous subtotal atrophy. Transmission electron microscope demonstrated several extracellular and intracellular rod-shaped bacteria (Tropheryma whipplei)...
January 2018: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/29133618/therapeutic-impact-of-nanoparticle-therapy-targeting-tumor-associated-macrophages
#12
Courtney A Penn, Kun Yang, Hong Zong, Jae-Young Lim, Alex Cole, Dongli Yang, James Baker, Sascha N Goonewardena, Ronald J Buckanovich
Antiangiogenic therapies, despite initial encouragement, have demonstrated a limited benefit in ovarian cancer. Laboratory studies suggest antiangiogenic therapy-induced hypoxia can induce tumor "stemness" as resistance to antiangiogenic therapy develops and limits the therapeutic benefit. Resistance to antiangiogenic therapy and an induction of tumor stemness may be mediated by proangiogenic tumor-associated macrophages (TAM). As such, TAMs have been proposed as a therapeutic target. We demonstrate here that ovarian TAMs express high levels of the folate receptor-2 (FOLR2) and can be selectively targeted using G5-dendrimer nanoparticles using methotrexate as both a ligand and a toxin...
January 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29062314/harnessing-apoptotic-cell-clearance-to-treat-autoimmune-arthritis
#13
REVIEW
Philippe Saas, Francis Bonnefoy, Eric Toussirot, Sylvain Perruche
Early-stage apoptotic cells possess immunomodulatory properties. Proper apoptotic cell clearance during homeostasis has been shown to limit subsequent immune responses. Based on these observations, early-stage apoptotic cell infusion has been used to prevent unwanted inflammatory responses in different experimental models of autoimmune diseases or transplantation. Moreover, this approach has been shown to be feasible without any toxicity in patients undergoing allogeneic hematopoietic cell transplantation to prevent graft- versus -host disease...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29056774/glucocorticoid-management-in-rheumatoid-arthritis-morning-or-night-low-dose
#14
REVIEW
Sabrina Paolino, Maurizio Cutolo, Carmen Pizzorni
Morning symptoms of rheumatoid arthritis (RA) are linked to circadian increase of night inflammation, supported by inadequate cortisol secretion in active disease. Therefore, exogenous glucocorticoid administration in RA is recommended by EULAR and ACR from the beginning of the diagnosis, since may partially act like a "replacement therapy". In addition, the prevention/treatment of the night up-regulation of the immune/inflammatory reaction has been shown more effective when exogenous glucocorticoid administration is managed with a night-time-release formulation...
2017: Reumatologia
https://www.readbyqxmd.com/read/28979343/the-potential-use-of-methotrexate-in-the-treatment-of-cutaneous-leishmaniasis-in-vitro-assays-against-sensitive-and-meglumine-antimoniate-resistant-strains-of-leishmania-tropica
#15
Hossein Mahmoudvand, Farnaz Kheirandish, Seyed Reza Mirbadie, Mohammad Hassan Kayedi, Tahereh Rezaei Riabi, Abbas Ali Ghasemi, Mehdi Bamorovat, Iraj Sharifi
BACKGROUND: The present study aimed to evaluate the effect of methotrexate (MTX) alone and in combination with meglumine antimoniate (MA, Glucantime) against sensitive and MA-resistant Leishmania tropica stages in vitro. METHODS: The present study was carried out in 2014 in Leishmaniasis Research Center at School of Medicine, Kerman University of Medical sciences, Kerman, Iran. The effects of MTX alone and along with MA on promastigote and amastigote stages of sensitive (SS) and MA-resistant (RS) L...
July 2017: Iranian Journal of Parasitology
https://www.readbyqxmd.com/read/28941039/a-randomized-phase-iib-study-of-mavrilimumab-and-golimumab-in-rheumatoid-arthritis
#16
Michael E Weinblatt, Iain B McInnes, Joel M Kremer, Pedro Miranda, Jiri Vencovsky, Xiang Guo, Wendy I White, Patricia C Ryan, Alex Godwood, Marius Albulescu, David Close, Gerd R Burmester
OBJECTIVE: This 24-week, phase IIb, double-blind study was undertaken to evaluate the efficacy and safety of mavrilimumab (a monoclonal antibody to granulocyte-macrophage colony-stimulating factor receptor α) and golimumab (a monoclonal antibody to tumor necrosis factor [anti-TNF]) in patients with rheumatoid arthritis (RA) who have had an inadequate response to disease-modifying antirheumatic drugs (DMARDs) (referred to as DMARD-IR) and/or inadequate response to other anti-TNF agents (referred to as anti-TNF-IR)...
January 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28932117/multifunctional-folate-receptor-targeting-and-ph-responsive-nanocarriers-loaded-with-methotrexate-for-treatment-of-rheumatoid-arthritis
#17
Jinlong Zhao, Menghui Zhao, Changhui Yu, Xueyan Zhang, Jiaxin Liu, Xinwei Cheng, Robert J Lee, Fengying Sun, Lesheng Teng, Youxin Li
Rheumatoid arthritis (RA) is an autoimmune disease characterized by progressive cartilage and bone destruction. Activated macrophages that overexpress folic acid (FA) receptors play an important role in RA, due to their abundance in inflamed synovial membrane and joints. In an effort to deliver drugs to the inflamed tissues, multifunctional FA receptor-targeting and pH-responsive nanocarriers were developed. They were composed of lipids, polyethylene glycol (PEG)-poly(lactic- co -glycolic acid) (PLGA) forming a hydrophilic shell, FA around the hydrophilic shell as a targeting ligand, and poly(cyclohexane-1,4-diylacetone dimethylene ketal) (PCADK) and PLGA as a hydrophobic core...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28871936/xanthoma-like-skin-changes-in-an-elderly-woman-with-a-normal-lipid-profile
#18
Piotr Nockowski, Zdzisław Woźniak, Adam Reich, Joanna Maj
Dear Editor, An 83-year-old woman developed yellow-brownish infiltrates, nodules, and tumors mimicking xanthomas, mostly involving the periorbital and chest area within three months (Figure 1). She had no abnormalities in serum cholesterol or triglycerides levels. A detailed laboratory analysis revealed the presence of mild monoclonal gammopathy with a presence of immunoglobulin G (IgG) kappa light chains; however, according to hematologist consultation, it did not require medical intervention. Imaging assessment and ultrasound examination did not show any specific involvement of internal organs...
July 2017: Acta Dermatovenerologica Croatica: ADC
https://www.readbyqxmd.com/read/28832763/methotrexate-associated-to-lipid-core-nanoparticles-improves-cardiac-allograft-vasculopathy-and-the-inflammatory-profile-in-a-rabbit-heart-graft-model
#19
A I Fiorelli, D D Lourenço-Filho, E R Tavares, P O Carvalho, A F Marques, P S Gutierrez, R C Maranhão, N A G Stolf
Coronary allograft vasculopathy is an inflammatory-proliferative process that compromises the long-term success of heart transplantation and has no effective treatment. A lipid nanoemulsion (LDE) can carry chemotherapeutic agents in the circulation and concentrates them in the heart graft. The aim of the study was to investigate the effects of methotrexate (MTX) associated to LDE. Rabbits fed a 0.5% cholesterol diet and submitted to heterotopic heart transplantation were treated with cyclosporine A (10 mg·kg-1·day-1 orally) and allocated to treatment with intravenous LDE-MTX (4 mg/kg, weekly, n=10) or with weekly intravenous saline solution (control group, n=10), beginning on the day of surgery...
August 17, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28754008/combination-therapy-of-peg-hm-3-and-methotrexate-retards-adjuvant-induced-arthritis
#20
Jingchao Hao, Xiaodong Wu, Sarra Setrerrahmane, Kun Qian, Yueying Hou, Liting Yu, Chenyu Lin, Qianqian Wu, Hanmei Xu
At present, the early phenomenon of inflammatory angiogenesis is rarely studied in Rheumatoid arthritis (RA). Previous research found that PEG-HM-3, an integrin inhibitor, possessed anti-angiogenesis and anti-rheumatic activity. In this study, the advantages of inhibiting angiogenesis and immune cell adhesion and migration, as well as the benefits of anti-arthritis effects, were evaluated using a combination of PEG-HM-3 and methotrexate (MTX). In vitro, spleen cell proliferation and the levels of tumor necrosis factor α (TNF-α) in macrophage supernatant were assessed...
July 21, 2017: International Journal of Molecular Sciences
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