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The results show that systemic levels of activated MMPs are reduced in RA patients upon exposure to leflunomide or methotrexate.
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The immunomodulatory drug leflunomide is frequently used for treating polyomavirus-associated nephropathy, yet its antiviral mechanism is unclear. We characterized the effects of the active leflunomide metabolite A771726 (LEF-A) on the polyomavirus BK (BKV) life cycle in human renal tubular epithelial cells. LEF-A at 10 microg/ml reduced the extracellular BKV load by 90% (IC(90)) but with significant host cytostatic effects. BKV genome replication, late protein expression, and virion assembly and release were inhibited with visible disruption of the nuclear replication architecture. Both host cell and antiviral effects were largely reversed by uridine addition, implicating nonspecific pyrimidine depletion as the major anti-BKV mechanism of leflunomide.
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To report the safety and efficacy of leflunomide (LEF) in combination with infliximab (INF) for the treatment of rheumatoid arthritis.
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Agents were reviewed with regard to mechanism of action, efficacy, drug interactions, pharmacokinetics, dosing, precautions/contraindications, adverse effects, and cost.
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The active metabolite (2) of the novel immunosuppressive agent leflunomide (1) has been shown to inhibit the enzyme dihydroorotate dehydrogenase (DHODH). This enzyme catalyzes the fourth step in de novo pyrimidine biosynthesis. A series of analogues of the active metabolite 2 have been synthesized. Their in vivo biological activity determined in rat and mouse delayed type hypersensitivity has been found to correlate well with their in vitro DHODH potency. The most promising compound (3) has shown activity in rat and mouse collagen (II)-induced arthritis models (ED50 = 2 and 31 mg/kg, respectively) and has shown a shorter half-life in man when compared with leflunomide. Clinical studies in rheumatoid arthritis are in progress.
These data suggests that leflunomide can prevent primary allergic sensitization and prevent allergen-induced EAR by inhibiting production of allergen-specific IgE antibodies. Further studies in atopic conditions are warranted.
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To investigate the safety and efficacy of leflunomide plus low-dose prednisolone for the maintenance of remission in Wegener's granulomatosis (WG).
Worldwide pomegranate (Punica granatum L.) production has expanded greatly due to recent evidence on the fruit health attributes. The fruit's unique red color, conferred by anthocyanins, is an imperative sensory quality. Climate effects on the fruit's internal color were reported earlier. The present study investigated the influence of a wide range of temperature regimes (∼7-40 °C) on pomegranates' aril anthocyanins. The study included two deciduous and two evergreen accessions as well as desert and Mediterranean orchards. RP-HPLC analysis of the arils' anthocyanins revealed mono- and diglucosylated delphinidins and cyanidins as the major anthocyanins and pelargonidins as minor components. Anthocyanin accumulation changed inversely to the season's temperatures. Cyanidins were generally more abundant but delphinidin accumulation was enhanced in cooler season. Monoglucosylated anthocyanins prevailed at cooler temperatures and subsided during seasonal warming with a concomitant increase in diglucoside proportion. The findings can benefit breeding and agricultural efforts to enhance pomegranate quality, especially in the face of "global warming".
To compare drug retention rates of non-aTNF-Bio with alternative aTNF.
to assess the security of the combined treatment with Methotrexate (MTX) and Leflunomide (LF) in patients with Rheumatoid Arthritis (RA) and to evaluate whether the dose and route of MTX administration influence on the toxicity.
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The clinical outcomes in patients with biopsy-proven BKVAN were unfavorable in the present study, especially in patients with advanced-stage BKVAN, poor renal function, and acute allograft rejection.
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Oral teriflunomide was effective in reducing MRI lesions and was well tolerated in patients with relapsing multiple sclerosis.
In this open study of patients with active AS only those with peripheral arthritis improved significantly with leflunomide treatment. Axial symptoms did not improve.
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Despite optimal therapy with disease-modifying antirheumatic drugs, many people with inflammatory arthritis (IA) continue to have persistent pain that may require additional therapy.
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The objective of this study was to evaluate the effectiveness of a sensorimotor training in patients with rheumatoid arthritis on the improvement of functional skills and quality of life, a double-blinded, prospective, randomized controlled trial. One hundred two participants with rheumatoid arthritis were selected. After the baseline evaluation, the participants were randomized to two different groups: sensorimotor group (2 sessions per week, 30-50 min each session, besides continuing taking the same drugs as the control group) and control group (control group was only submitted to the clinical drug treatment with Methotrexate, Leflunomide and/or Prednisone (5 mg), being then evaluated 4 months later). Functional capacity [Health Assessment Questionnaire (HAQ) and Timed Up & Go Test (TU>)], Balance and Gait (Berg Balance Scale (BBS) and Tinetti Test) and Quality of Life (Short Form Health Survey-SF-36). The study had been concluded with ninety-one participants, and a statistically significant improvement was found in all variables assessed: HAQ (P < .01), TU> (P < .01), BBS (P < .01), Tinetti Test (P < .01) and improvement in the subscales of SF-36 (P < .01) in the sensorimotor group in comparison with the baseline evaluation and control group. No significant difference was found related to the pre- and post-evaluation in the control group. Therefore, the sensorimotor training is effective in the improvement of the functional capacity and quality of life of patients with rheumatoid arthritis.
Leflunomide has been identified as an immunoregulatory and anti-inflammatory compound. Allergic disease is characterized by elevated serum IgE levels, production of allergen-specific IgE and the release of inflammatory mediators from mast cells and granulocytes. Here we demonstrate, using an in vivo murine model, the ability of leflunomide to down-regulate levels of total and allergen-specific serum IgE production. Mice receiving leflunomide (45 mg/kg) orally at the time of primary immunization with ovalbumin adsorbed to aluminium hydroxide adjuvant, showed a reduction in total serum IgE levels of 95%, 41% and 32% following primary, secondary and tertiary immunizations, respectively (P < 0.05). When leflunomide was administered both at the time of primary and subsequent immunizations, reductions in total and specific serum IgE levels of > 80% and > 38%, respectively, were observed (P < 0.05). Administration of leflunomide to mice which had already developed an IgE response resulted in reductions in total and specific serum IgE levels of > 80% and > 45%, respectively (P < 0.05). Following leflunomide treatment, animals failed to develop immediate cutaneous hypersensitivity responses when challenged intradermally with allergen. Down-regulation of immunoglobulin production was not restricted to IgE, since levels of allergen-specific IgG1 and IgG2a in serum were also reduced. The finding of significant reductions in total and allergen-specific IgM suggests that the mechanism of action does not involve selective inhibition of immunoglobulin class switching. A loss in production of the T helper cell-derived B cell differentiation factor IL-5 may account for the reduction in immunoglobulin levels. In adoptive transfer experiments leflunomide did not induce tolerance in allergen-reactive Th2 populations, contrary to animal disease models of transplantation and autoimmunity, where leflunomide was shown to induce tolerance in the effector T cell population.
To investigate the risk of hepatitis B virus (HBV) reactivation in rheumatoid arthritis (RA) patients with HBV carrier state during treatment of disease-modifying antirheumatic drugs (DMARDs) and the use of antiviral prophylaxis in real-world clinical practice.
Kimura's disease (KD) with renal involvement is a rare disease. Optimal treatments are still not well established. It is necessary to analyze clinicopathological features, treatment responses, and prognosis for improving KD diagnosis and treatment.
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This paper reviews recent approaches to treatment of early rheumatoid arthritis (RA) with disease-modifying antirheumatic drugs (DMARDs). The literature on treatment the early RA published between 1995 and 2007 was accessed through the PubMed database from the National Library of Medicine. Keywords were 'early rheumatoid arthritis', 'disease-modifying antirheumatic drugs', 'biologic agents' and 'combination therapy'. Only results of trials on human subjects that directly measured the effects of DMARDs or biological agents on clinical, laboratory parameters and radiological progression of early RA were selected. Combination therapy suppresses RA activity and radiological progression more effectively than monotherapy. If better control of RA is evident after 3-6 months of treatment with the combination of DMARDs, one must still decide whether to stop the first DMARD, stop the second, or continue with the combination. Combination therapy biological agents (infliximab, adalimumab) with methotrexate and etanercept therapy alone may induce remission in many patients with early RA. It is a method of choice in patients with an adverse prognosis. The main indications for combination therapy 'standard' DMARDs or combination 1 DMARDs with a biological agent are such variables as detection of a shared epitope, increase of concentration of anticyclic citrullinated peptide antibodies, rheumatoid factor, C-reactive protein, 28-joint disease activity score, Sharp score and presence of erosion in joints. The majority of rheumatologists believe that patients with RA should be treated with DMARDs earlier rather than later in the disease process. Further trials should establish the optimal approaches to early RA therapy.
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Seven recommendations about pharmacotherapy in patients with AS were developed. They can be expected to improve clinical practice uniformity and, in the longer term, to optimize the management of patients with AS in France.