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Macrophage methotrexate

Muhammad Sarfraz, Wilson Roa, Nadia Bou-Chacra, Raimar Löbenberg
Secondary macrophage cytotoxicity induced by nanoparticles was described before. The study aim was to investigate the role of secondary cytotoxic effect in a macrophage-lung cancer coculture model after nanoparticle treatment in the presence and absence of anti-inflammatory drugs. An in vitro coculture model composed of confluent alveolar macrophage MH-S and A-549 lung cancer cells separated by a 0.4 μm porous membrane was used in the study. Macrophages were treated with two sizes of gelatin nanoparticles and two sizes of poly(isobutyl cyanoacrylate) (PIBCA) nanoparticles, with and without doxorubicin as a chemotherapeutic drug...
September 6, 2016: Molecular Pharmaceutics
Leandro Gonzaga De Oliveira, Letîcia Aparecida Figueiredo, Gabriella Maria Fernandes-Cunha, De Miranda Marina Barcelos, Laser Antonio Machado, Gisele Rodrigues Dasilva, De Moura Sandra Aparecida Lima
In this study, the methotrexate (MTX) was incorporated into the poly(e-caprolactone) (PCL) to design implants (MTX PCL implants) aiming the local treatment of inflammatory angiogenesis diseases without causing systemic side effects. Sponges were inserted into the subcutaneous tissue of mice as a framework for fibrovascular tissue growth. After 4days, MTX PCL implants were also introduced, and anti-inflammatory, antiangiogenic, and antifibrogenic activities of the MTX were determined. MTX reduced the vascularization (hemoglobin content), the neutrophil, and monocyte/macrophage infiltration (MPO and NAG activities, respectively), and the collagen deposition in sponges...
November 2015: Journal of Pharmaceutical Sciences
A Torrelo, L Noguera-Morel, A Hernández-Martín, D Clemente, J M Barja, L Buzón, D Azorín, A A de Jesús, J C López-Robledillo, I Colmenero, H Kutzner, R Goldbach-Mansky, L Requena
BACKGROUND: Recurrent panniculitis in children with lipoatrophy has been loosely described and reported under different names, but has never been systematically evaluated by immunohistochemical stains. OBJECTIVE: To depict the profile of children with recurrent idiopathic panniculitis. METHODS: Study of clinical, histopathological and immunohistochemical features in five cases with recurrent idiopathic panniculitis. RESULTS: Five children with repeated attacks of painful subcutaneous nodules in association with fever, malaise and abdominal pain or arthralgia, with subsequent lipoatrophy were reviewed...
August 12, 2016: Journal of the European Academy of Dermatology and Venereology: JEADV
Elisabetta Caiazzo, Francesco Maione, Silvana Morello, Andrea Lapucci, Sara Paccosi, Bodo Steckel, Antonio Lavecchia, Astrid Parenti, Teresa Iuvone, Jürgen Schrader, Armando Ialenti, Carla Cicala
Extracellular adenosine formation from ATP is controlled by ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase/CD39) and ecto-5'-nucleotidase (e-5NT/CD73); the latter converts AMP to adenosine and inorganic phosphate, representing the rate limiting step controlling the ratio between extracellular ATP and adenosine. Evidence that cellular expression and activity of CD39 and CD73 may be subject to changes under pathophysiological conditions has identified this pathway as an endogenous modulator in several diseases and was shown to be involved in the molecular mechanism of drugs, such as methotrexate, salicylates , interferon-β...
July 15, 2016: Biochemical Pharmacology
Eugénia Nogueira, Andreia Gomes, Ana Preto, Artur Cavaco-Paulo
Rheumatoid arthritis is a common chronic inflammatory and destructive arthropathy that consumes considerable personal, social and economic costs. It consists of a syndrome of pain, stiffness and symmetrical inflammation of the synovial membrane (synovitis) of freely moveable joints such as the knee (diarthrodial joints). Although the etiology of rheumatoid arthritis is unclear, the disease is characterized by inflammation of the synovial lining of diarthrodial joints, high synovial proliferation and an influx of inflammatory cells, macrophages and lymphocytes through angiogenic blood vessels...
2016: Current Medicinal Chemistry
Katsuaki Kanbe, Koei Oh, Junji Chiba, Yasuo Inoue, Masashi Taguchi, Akiko Yabuki
The aim of this study was to analyze the histological changes related to mitogen-activated protein (MAP) kinases in bone and cartilage treated with abatacept for rheumatoid arthritis (RA). A total of 20 patients of bone and cartilage were assessed: 10 abatacept with methotrexate (MTX)-treated RA patients were compared with 10 MTX-treated RA patients (control). The histology of bone and cartilage was observed by staining with hematoxylin and eosin and analyzed immunohistochemically for the expression of tumor necrosis factor-α, interleukin-6, CD4 (T cell), CD68 (macrophage), receptor activator of nuclear kappa-B ligand, osteoprotegerin, osteopontin, CD29 (β-1 integrin), phospho-p38 MAPK (Tyr180/Tyr182), phospho-p44/42 MAPK (extracellular signal-regulated kinase, ERK1/ERK2), and phosphor-c-Jun N-terminal kinase...
2016: Clinical Medicine Insights. Arthritis and Musculoskeletal Disorders
Betul Sozeri, Basak Yildiz Atikan, Kadriye Ozdemir, Sevgi Mir
An increased incidence of cardiovascular disease has been found in rheumatic disorders. Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children. Prolonged immunological inflammatory process leads these patients to an early onset of atherosclerosis. We aimed to assess the presence of early vascular dysfunction in patients with systemic onset juvenile idiopathic arthritis (sJIA) and investigate the role of therapy sJIA in vascular health. Thirty-three patients (22 males, 11 females) diagnosed with sJIA according to the International League of Associations for Rheumatology criteria were compared to 72 age- and sex-matched controls...
July 2016: Clinical Rheumatology
Michelle J Ormseth, Patricia G Yancey, Joseph F Solus, S Louis Bridges, Jeffrey R Curtis, MacRae F Linton, Sergio Fazio, Sean S Davies, L Jackson Roberts, Kasey C Vickers, Valentina Kon, C Michael Stein
OBJECTIVE: Patients with rheumatoid arthritis (RA) have an increased risk of coronary heart disease (CHD). Some RA therapies may modify this risk, but the underlying mechanisms are unclear. The cholesterol efflux capacity of high-density lipoprotein (HDL) is associated with a reduced CHD risk in non-RA populations; however, inflammation may impair the function of HDL. The aim of this study was to evaluate whether reduced inflammation resulting from treatment with methotrexate (MTX), adalimumab (ADA), or tocilizumab (TCZ) would increase the net cholesterol efflux capacity of HDL in patients with RA...
September 2016: Arthritis & Rheumatology
Rachit Shah, Jacob Petersburg, Amit C Gangar, Adrian Fegan, Carston R Wagner, Sidath C Kumarapperuma
Chemically self-assembled nanorings (CSANs) are made of dihydrofolate reductase (DHFR) fusion proteins and have been successfully used in vitro for cellular cargo delivery and cell surface engineering applications. However, CSANs have yet to be evaluated for their in vivo stability, circulation, and tissue distribution. In an effort to evaluate CSANs in vivo, we engineered a site-specifically PEGylated epidermal growth factor receptor (EGFR) targeting DHFR molecules, characterized their self-assembly into CSANs with bivalent methotrexates (bis-MTX), visualized their in vivo tissue localization by microPET/CT imaging, and determined their ex vivo organ biodistribution by tissue-based gamma counting...
July 5, 2016: Molecular Pharmaceutics
Maurizio Cutolo, Sabrina Paolino, Carmen Pizzorni, Alberto Sulli, Bruno Seriolo, Marco Amedeo Cimmino, Paola Montagna, Stefano Soldano, Paola Contini, Renata Brizzolara
OBJECTIVES: To evaluate the anti-inflammatory effect of CTLA4-Ig (abatacept) and dexamethasone (DEX) monotreatment versus their combination and adding methotrexate (MTX) on cultured human macrophages. METHODS: THP-1 cells, activated into macrophages (PMA 0.05 μg/ml), were cultured for 3 and 24 hrs with CTLA4-Ig (500 μg/ml), DEX (10-8 M), MTX (0.05 μg/ml), and CTLA4-Ig combined with DEX or CTLA4-Ig combined with DEX plus MTX. CTLA4-Ig/CD86 interaction was evaluated by FACS analysis...
May 2016: Clinical and Experimental Rheumatology
Cristina Municio, Blanca Soler Palacios, Lizbeth Estrada-Capetillo, Alberto Benguria, Ana Dopazo, Elena García-Lorenzo, Salvador Fernández-Arroyo, Jorge Joven, María Eugenia Miranda-Carús, Isidoro González-Álvaro, Amaya Puig-Kröger
OBJECTIVES: Methotrexate (MTX) functions as an antiproliferative agent in cancer and an anti-inflammatory drug in rheumatoid arthritis (RA). Although macrophages critically contribute to RA pathology, their response to MTX remains unknown. As a means to identify MTX response markers, we have explored its transcriptional effect on macrophages polarised by GM-CSF (GM-MØ) or M-CSF (M-MØ), which resemble proinflammatory and anti-inflammatory macrophages found in RA and normal joints, respectively...
February 26, 2016: Annals of the Rheumatic Diseases
Eugénia Nogueira, Franck Lager, Delphine Le Roux, Patrícia Nogueira, Jaime Freitas, Celine Charvet, Gilles Renault, Ana Loureiro, Catarina R Almeida, Anna Ohradanova-Repic, Christian Machacek, Gonçalo J L Bernardes, Alexandra Moreira, Hannes Stockinger, Michael Burnet, Alexandre M Carmo, Andreia C Gomes, Ana Preto, Georges Bismuth, Artur Cavaco-Paulo
Methotrexate is the first line of treatment of rheumatoid arthritis. Since many patients become unresponsive to methotrexate treatment, only very expensive biological therapies are effective and increased methotrexate tolerance strategies need to be identified. Here we propose the encapsulation of methotrexate in a new liposomal formulation using a hydrophobic fragment of surfactant protein conjugated to a linker and folate to enhance their tolerance and efficacy. In this study we aim to evaluate the efficiency of this system to treat rheumatoid arthritis, by targeting folate receptor β present at the surface of activated macrophages, key effector cells in this pathology...
December 2015: Journal of Biomedical Nanotechnology
Yasemin Işık Balcı, Funda Özgürler Akpınar, Aziz Polat, Fethullah Kenar, Bianca Tesi, Tatiana Greenwood, Nagihan Yalçın, Ali Koçyiğit
Hemophagocytic lymphohistiocytosis (HLH) represents a severe hyperinflammatory condition with cardinal symptoms of prolonged fever, cytopenias, hepatosplenomegaly, and hemophagocytosis by activated, morphologically benign macrophages with impaired function of natural killer cells and cytotoxic T lymphocytes. A 2-month-old girl, who was admitted with fever, was diagnosed with HLH and her genetic examination revealed a newly defined mutation in the UNC13D (c.175G>C; p.Ala59Pro) gene. She was treated with dexamethasone, etoposide, and intrathecal methotrexate...
December 2015: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
Takashi Sasayama, Kazuhiro Tanaka, Takashi Mizowaki, Hiroaki Nagashima, Satoshi Nakamizo, Hirotomo Tanaka, Masamitsu Nishihara, Katsu Mizukawa, Takanori Hirose, Tomoo Itoh, Eiji Kohmura
Increased tumor-associated macrophages (TAMs) have been reported to be associated with poor prognosis in various tumors; however, the importance of TAMs in primary central nervous system lymphoma (PCNSL) has not been clarified. In 47 patients with PCNSL who were treated with high-dose methotrexate (MTX) and radiotherapy, the relationships between the infiltration levels of TAMs and the clinicopathological parameters were analyzed. Univariate analysis of the Cox proportional hazards model using continuous scales revealed that increased CD68 positive (+) TAMs was significantly associated with inferior progression-free survival (PFS) (P = 0...
July 2016: Brain Pathology
Rong Qi, Istvan Majoros, Asish C Misra, Alisa E Koch, Phil Campbell, Hubert Marotte, Ingrid L Bergin, Zhengyi Cao, Sascha Goonewardena, Jingga Morry, Shuai Zhang, Michael Beer, Paul Makidon, Alina Kotlyar, Thommey P Thomas, James R Baker
Generation 5 (G5) poly(amidoamide) (PAMAM) dendrimers are synthetic polymers that have been broadly applied as drug delivery carriers. Methotrexate (MTX), an anti-folate metabolite, has been successfully used as an anti-inflammatory drug to treat rheumatoid arthritis (RA) in the clinic. In this study, we examine the therapeutic efficacy of G5 PAMAM dendrimer methotrexate conjugates (G5-MTX) that also have folic acid (FA) conjugated to the G5-MTX (G5-FA-MTX) to target inflammation-activated folate receptors overexpressing macrophages...
August 2015: Journal of Biomedical Nanotechnology
Samy Selim, Soad Al Jaouni
Costus speciosus is an important medicinal plant widely used in several indigenous medicinal formulations. The present study was conducted to evaluate the in vitro anti-inflammatory, antioxidant and antiangiogenic activities of diosgenin isolated from C. speciosus. The diosgenin was isolated from C. speciosus by HPTLC and its biological activities were studied by different protocols. The results demonstrated that LPS stimulated TNF-α generation in RAW 264.7 macrophage culture supernatant up to 3.7-fold of the control and that sample treatment (50 μg/mL) resulted in a highly significant inhibitory effect on LPS-stimulated TNF-α (p < 0...
August 2016: Natural Product Research
Leandro Gonzaga De Oliveira, Letícia Aparecida Figueiredo, Gabriella Maria Fernandes-Cunha, Marina Barcelos De Miranda, Laser Antônio Machado, Gisele Rodrigues Da Silva, Sandra Aparecida Lima De Moura
In this study, the methotrexate (MTX) was incorporated into the poly(ε-caprolactone) (PCL) to design implants (MTX PCL implants) aiming the local treatment of inflammatory angiogenesis diseases without causing systemic side effects. Sponges were inserted into the subcutaneous tissue of mice as a framework for fibrovascular tissue growth. After 4 days, MTX PCL implants were also introduced, and anti-inflammatory, antiangiogenic, and antifibrogenic activities of the MTX were determined. MTX reduced the vascularization (hemoglobin content), the neutrophil, and monocyte/macrophage infiltration (MPO and NAG activities, respectively), and the collagen deposition in sponges...
November 2015: Journal of Pharmaceutical Sciences
Jing-Fen Jin, Ling-Ling Zhu, Meng Chen, Hui-Min Xu, Hua-Fen Wang, Xiu-Qin Feng, Xiu-Ping Zhu, Quan Zhou
BACKGROUND: Intravenous (IV), intramuscular (IM), and subcutaneous (SC) are the three most frequently used injection routes in medication administration. Comparative studies of SC versus IV, IM versus IV, or IM versus SC have been sporadically conducted, and some new findings are completely different from the dosage recommendation as described in prescribing information. However, clinicians may still be ignorant of such new evidence-based findings when choosing treatment methods. METHODS: A literature search was performed using PubMed, MEDLINE, and Web of Sciences™ Core Collection to analyze the advantages and disadvantages of SC, IV, and IM administration in head-to-head comparative studies...
2015: Patient Preference and Adherence
João Albuquerque, Catarina Costa Moura, Bruno Sarmento, Salette Reis
Rheumatoid arthritis (RA) is the most common joint-related autoimmune disease and one of the most severe. Despite intensive investigation, the RA inflammatory process remains largely unknown and finding effective and long lasting therapies that specifically target RA is a challenging task. This study proposes a different approach for RA therapy, taking advantage of the new emerging field of nanomedicine to develop a targeted theranostic system for intravenous administration, using solid lipid nanoparticles (SLN), a biocompatible and biodegradable colloidal delivery system, surface-functionalized with an anti-CD64 antibody that specifically targets macrophages in RA...
2015: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Esthela Loyo, Luis J Jara, Persio David López, Ana Carolina Puig
Autoimmune/autoinflammatory syndrome induced by adjuvants (ASIA) has been recently proposed by Shoenfeld and Agmon-Levin as a new entity that comprises several conditions: the macrophagic-myofasciitis syndrome, the Gulf War syndrome, silicosis and post-vaccination phenomena, autoimmunity related to infectious fragments, hormones, aluminum, silicone, squalene oil, and pristane. We report the case of a 23-year-old woman who developed serial episodes of high fever, extreme fatigue, transient thrombocytopenia, multiple cervical adenopathies, hepatosplenomegaly, anemia, neutropenia, severe proteinuria and urine sediment abnormalities, elevated serum ferritin levels, and transient low positive antinuclear antibodies 1 year after she had a nickel-titanium chin implant for cosmetic reasons...
April 2013: Auto- Immunity Highlights
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