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CLIC1 Expression in Skin Biopsies from Patients With Rheumatoid and Psoriatic Arthritis as a Potential Tool to Predict Therapy Response.

BACKGROUND/AIM: Chloride intracellular channel protein 1 (CLIC1) activates inflammasomes in rheumatoid (RA) and psoriatic (PsA) arthritis. We studied CLIC1 expression in RA and PsA patients' skin with vasculitis and its variability depending on the therapy used. MATERIALS AND METHODS: CLIC1 immunoexpression was evaluated in the vascular (CLIC1-V) and stromal (CLIC1-S) compartments of the RA and PsA skin biopsies of patients treated with methotrexate (MTX), leflunomid (LFN), corticotherapy (CT), or biological therapies. RESULTS: MTX significantly reduced CLIC1-S expression (p=0.016), whereas

Effects of dihydroorotate dehydrogenase (DHODH) inhibitors on the growth of Theileria equi and Babesia caballi in vitro.

Theileria equi and Babesia caballi are the causative agents of equine piroplasmosis (EP), which affects equine production in various parts of the world. However, a safe and effective drug is not currently available for treatment of EP. Dihydroorotate dehydrogenase (DHODH) is the fourth enzyme in the de novo pyrimidine synthesis pathway and has been known as a novel drug target for several apicomplexan protozoan parasites. In this study, we evaluated four DHODH inhibitors; atovaquone (ATV), leflunomide (LFN), brequinar (Breq), and 7-hydroxy-5-[1,2,4] triazolo [1,5,a] pyrimidine (TAZ) on the gro…

Old and new antirheumatic drugs and the risk of hepatotoxicity.

Given the high prevalence of the use of medications in daily practice and the large number of people taking antirheumatic agents, the risk o … owledge about drug-specific, class-specific reactions. Some drugs (sulfasalazine, azathioprine, and leflunomide) may cause acute liver injury, whereas other compounds (methotrexate) may cause chronic liver damage as the result of the interaction among drug, host and environmental factors. The tumor necrosis factor-alpha inhibitor, infliximab, is associated wi …

Psoriatic arthritis: treatment strategies using anti-inflammatory drugs and classical DMARDs.

Psoriatic Arthritis (PsA) is a chronic inflammatory disease typically characterized by arthritis and psoriasis variably associated with othe … ost widely used DMARDs are methotrexate (level of evidence B), sulfasalazine (level of evidence A), leflunomide (level of evidence A), and ciclosporin (level of evidence B). However, the efficacy of these agents in inhibiting joint erosions has not been assessed in controlled studies. Finally, the effectiveness of DMARDs in treating enthesitis and dactylitis …

[Rituximab in the treatment of acquired haemophilia A in a patient with polymyalgia rheumatica].

UNLABELLED: Acquired hemophilia A is a rare but potentially life-threatening bleeding disorder. It is caused by the development of autoantibodies directed against coagulation factor VIII in adults or elderly patients, who do not have a personal or family history of bleeding. CASE: A man (age: 76 years) on prednisone and leflunomide for polymyalgia rheumatica developed spontaneous severe haematomas. The patient was diagnosed with acquired factor VIII deficiency (FVIII activity 1.2%, FVIII inhibitor 31.7 BU). Due to the active bleeding diathesis, treatment was administered with activated prothr…

Вирусы и артрит: новые задачи в области диагностики, лечения и иммунизации.

Несмотря на то, что многие вирусы вызывают симптомы мускулоскелета во время острой инфекции, долгосрочный подстрекательский артрит остается необычным последствием. При оценке артрита у пациента с хронической или скрытой вирусной инфекцией серологическое тестирование и терапевтические методы существенно изменяются. РЕЗУЛЬТАТЫ: Пример гепатита С показывает, как хроническая инфекция может осложнить диагностику ревматоидного артрита. Определение коэффициента ревматоида имеет ограниченную полезность, в то время как антициклический цитуллинированный пептид стал новым испытанием с улучшенной специфик

Совпадение в аннотации оригинала
BACKGROUND: Although many viruses produce musculoskeletal symptoms during an acute infection, a long-term inflammatory arthritis remains an … re severely constrained because of potential hepatotoxicity of oral agents such as methotrexate and leflunomide. Antitumor necrosis factor alpha biologics have demonstrated initial safety in the setting of hepatitis C virus but may be associated with reactivation of hepatitis B virus. Biologics such as abatacept and rituximab have been inadequately studied in …

BK virus nephritis after renal transplantation.

BK viremia and nephritis are increasing problems in renal transplant recipients. The exact cause of the increasing prevalence of this condit … s (BKVN) consists of reduction in immunosuppressive therapy and antiviral therapy with cidofovir or leflunomide or a combination of both. Approximately 30-60% of subjects with BKVN experienced irreversible graft failure. However, in recent years, the combinations of early detection, prompt diagnosis, and appropriate reduction in immunosuppressive therapy have …

[Not Available].

Juvenile idiopathic arthritis is a chronic inflammatory disease with uncertain outcome. Patients may suffer from severe joint damage leading … led trials to be effective. Other immunosuppressive drugs such as azathioprine, cyclosporine A, and leflunomide have not yet been investigated sufficiently. In addition, there is no scientific basis for the application of gold salts or (hydroxy)chloroquine. New therapeutic biologic agents, notably the tumor necrosis factor inhibitors, have achieved dramatic i …

A retrospective study on the predictive implications of clinical characteristics and therapeutic management in patients with rheumatoid arthritis-associated interstitial lung disease.

BACKGROUND: Rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) is associated with significant morbidity and is a critical … D. No correlation was found between ILD development and traditional DMARDs such as methotrexate and leflunomide. According to the follow-up data, 83 RA-ILD patients were identified as interstitial lung disease (ILD) progression, and 102 participants were stable. Logistic regression modeling demonstrated that DLCO% < 45% (OR: 3.025) and UIP possible pattern on …

Is Baricitinib Effective and Safe for Patients with Difficult-to-Treat Rheumatoid Arthritis? Comparative Data with the Rheumatoid Arthritis Group of Rheumatoid Arthritis Not Difficult to Treat.

OBJECTIVE: This study investigates the efficacy and safety of baricitinib, an oral targeted synthetic disease-modifying antirheumatic drugs … nd non-D2T RA groups, whether treated with baricitinib alone or in combination with methotrexate or leflunomide. CONCLUSION: Despite potential treatment resistance, patients meeting the D2T RA criteria shared similar safety and efficacy profiles with those non-D2T RA. Baricitinib emerges as a promising treatment option for D2T RA patients, offering effective …

New therapeutic options in sarcoidosis.

PURPOSE OF REVIEW: Corticosteroids remain the cornerstone of sarcoidosis treatment but are associated with significant toxicities and impaired quality of life. Second-line and third-line treatments include hydroxychloroquine or immunosuppressants (methotrexate, azathioprine, leflunomide and mycophenolate mofetil), and anti-TNF-α agents (infliximab and adalimumab), respectively. The latest identification of significant key cellular pathways in sarcoidosis pathogenesis has led to the development of new therapeutic strategies described in this review. RECENT FINDINGS: JAK inhibitors, mainly tofa…

Comparison of disease-modifying anti-rheumatic drugs and hyperbaric oxygen therapy in the experimental model of rheumatoid arthritis in rats.

In this study, we wanted to investigate the effectiveness of combining disease-modifying anti-rheumatic drugs (DMARD) with hyperbaric oxygen therapy (HBOT) in reducing inflammation in a rheumatoid arthritis (RA) model using rats. We divided 56 male Sprague-Dawley rats into seven groups and induced RA using complete Freund's adjuvant. Some groups received HBOT, whereas others were given etanercept or leflunomide. We started the treatment on the 10th day after inducing RA and continued it for 18 days. To evaluate the effectiveness of the treatments, we measured paw swelling and used X-rays to ex…

Investigational agents for polymyalgia rheumatica treatment: assessing the critical needs for future development.

INTRODUCTION: Polymyalgia rheumatica (PMR) is an inflammatory rheumatic disorder characterized by pain and stiffness in the shoulder and pel … MR patients. Currently, there are 12 ongoing clinical trials exploring potential treatments such as leflunomide, low-dose IL-2, rituximab, abatacept, secukinumab, Janus kinase inhibitors, and selective inhibitors like SPI-62 and ABBV 154. EXPERT OPINION: The high efficacy of IL-6 R receptor inhibitors as well as the numerous drug trials currently recruiting …

Native BK Polyomavirus Nephropathy in an Orthotopic Heart Transplant Patient.

BK polyomavirus nephropathy (BKVN) is a common cause of nephropathy in kidney transplant patients and is typically seen within the first yea … irus nephritis. Serum BK viral load was elevated. Despite reducing immunosuppression and initiating leflunomide, viral clearance was never achieved. The patient experienced progressive failure to thrive before ultimately transitioning to hospice care and dying. The intensity of immunosuppression is a well-known risk factor for viral replication; ureteral sten …

Multicentric Reticulohistiocytosis Exhibiting Positive HLA-B*07 and HLA-B*08: A Case Report.

Multicentric reticulohistiocytosis (MRH) is a rare cause of destructive inflammatory arthritis involving both small, as well as larger joint … quent giant multinucleated cells. The patient exhibited favorable outcomes under Methotrexate, then Leflunomide. However, she displayed worsening clinical symptoms while under Azathioprine. To our knowledge, this is the first case of MRH to exhibit positive HLA-B*07 together with HLA-B*08. The rarity of MRH, its unknown etiology and polymorphic clinical prese …

JAK inhibition by methotrexate (and csDMARDs) may explain clinical efficacy as monotherapy and combination therapy.

Methotrexate (MTX) is recognized as the anchor drug in the algorithm treating chronic arthritis (RA, psoriatic arthritis), as well as a ster … . The MTX effects on JAK1/JAK2 inhibition also allows to understand why the combination of MTX with Leflunomide, or JAK1/JAK3 inhibitor leads to better clinical outcomes than monotherapy, while the combination with JAK1/JAK2 or JAK1 specific inhibitors does not seem to exert additive clinical benefit.

Polo-like-kinase 1 (PLK1) as a molecular target to overcome SYK-mediated resistance of B-lineage acute lymphoblastic leukaemia cells to oxidative stress.

SYK tyrosine kinase has emerged as a master regulator of cellular resistance to oxidative stress (OS) by mediating the activation of the anti-apoptotic nuclear factor kappaB and phosphatidylinositol-3 kinase/AKT pathways after OS exposure. Here, we present unprecedented experimental evidence that polo-like kinase 1 (PLK1) is the upstream regulator of SYK in B-lineage acute lymphoblastic leukaemia (ALL) cells. Selective inhibition of PLK-1 with the leflunomide metabolite analogue alpha-cyano-beta-hydroxy-beta-methyl-N-[4-(trifluoromethoxy) phenyl]-propenamide/LFM-A12 abolished the resistance of…

Combination of Endoscopic Resection and Heat Ablation Is a Promising Endoscopic Therapy for Adenoma-Like Dysplastic Lesion in Chronic Ulcerative Colitis.

INTRODUCTION: Rheumatoid arthritis (RA) is an autoimmune disease whose treatment has evolved with the introduction of disease-modifying antirheumatic drugs and biological agents such as rituximab (RTX). The objective of this study was to evaluate the efficacy, safety, and treatment adherence of RTX used as monotherapy and in combination with methotrexate (MTX) or leflunomide (LFN) in patients with RA refractory to conventional therapy. MATERIAL AND METHODS: A prospective cohort study was conducted including 157 patients, divided into 3 groups: RTX monotherapy (n = 48), RTX + MTX (n = 66), and…

Successful use of a Janus-kinase (JAK) inhibitor in chronic chikungunya arthritis refractory to conventional synthetic DMARDs: a case report.

Chronic chikungunya arthritis is a debilitating post-viral inflammatory condition that clinically mimics rheumatoid arthritis and often requ … introduced but was discontinued after three weeks due to drug-induced pneumonitis. She later failed leflunomide therapy after 12 months, with a score of 4.33. Baricitinib (4 mg/day), a Janus kinase 1 and 2 inhibitor, was then initiated, resulting in marked clinical and laboratory improvement: the disease activity score decreased to 1.90 over one year, C-react …

Modified proposomes as a novel intra-articular delivery approach for rheumatoid arthritis.

A novel intra-articular (IA) nanocarrier system for leflunomide (LEF) was developed using modified proposomes to enhance therapeutic efficacy in rheumatoid arthritis (RA). LEF was efficiently encapsulated within propylene glycol-based proposomes, which were sequentially functionalised with chitosan (CS) and hyaluronic acid (HA) to improve stability, bioadhesion and targeted delivery. The optimised nanoparticles exhibited a uniform nanoscale size, a zeta potential of -50.46 ± 6.4 mV, and a high entrapment efficiency of 94.12 ± 1.7%. In vitro release studies revealed a sustained LEF release prof…