Search results for "OSiS"
showing 10 items of 15931 documents
Retinal abnormalities in multiple sclerosis patients with associated chronic cerebrospinal venous insufficiency
2012
Optical coherence tomography (OCT) is a non-invasive method for the assessment of optic nerve fibers and retinal ganglion cells. This study was aimed at the assessment of retinal abnormalities in multiple sclerosis patients in the context of chronic cerebrospinal venous insufficiency using OCT of the retina and the optic nerve. We examined 239 multiple sclerosis (MS) patients, including 220 patients with associated chronic cerebrospinal venous insufficiency and 19 MS patients without venous pathology. The following OCT parameters were assessed: average ganglion cell complex thickness, global loss volume, focal loss volume and average retinal nerve fibre layer thickness. Abnormalities in the…
Inflammatory cytokines shape a changing DNA methylome in monocytes mirroring disease activity in rheumatoid arthritis
2019
Objective: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that mainly targets joints. Monocytes and macrophages are critical in RA pathogenesis and contribute to inflammatory lesions. These extremely plastic cells respond to extracellular signals which cause epigenomic changes that define their pathogenic phenotype. Here, we interrogated how DNA methylation alterations in RA monocytes are determined by extracellular signals. Methods: High-throughput DNA methylation analyses of patients with RA and controls and in vitro cytokine stimulation were used to investigate the underlying mechanisms behind DNA methylation alterations in RA as well as their relationship with clinic…
Good clinical response, remission, and predictors of remission in rheumatoid arthritis patients treated with tumor necrosis factor-α blockers: The GI…
2007
OBJECTIVE: To assess the prevalence of good clinical response and remission in rheumatoid arthritis (RA) patients with longstanding disease treated with anti-tumor necrosis factor-alpha (TNF-alpha) drugs at outpatient clinics. METHODS: Retrospective national study of 14 academic tertiary referral rheumatology medical centers. RA patients with a Disease Activity Score (DAS28) > 3.2 were defined as having active disease and could start TNF-alpha blockers. All patients received one TNF-alpha blocker plus methotrexate (10-20 mg/wk). At the third month the patients were categorized as responders or nonresponders, based on improvement of at least 0.25 of the Health Assessment Questionnaire (HAQ).…
Etanercept maintains the clinical benefit achieved by infliximab in patients with rheumatoid arthritis who discontinued infliximab because of side ef…
2007
Objective: To evaluate the efficacy of switching to etanercept treatment in patients with rheumatoid arthritis who already responded to infliximab, but presented side effects. Methods: Charts of 553 patients with rheumatoid arthritis were retrospectively reviewed to select patients who responded to the treatment with infliximab and switched to etanercept because of occurrence of adverse effects. Clinical data were gathered during 24 weeks of etanercept treatment and for the same period of infliximab treatment before infliximab was stopped. Disease Activity Score computed on 44 joints (DAS-44), erythrocyte sedimentation rate (ESR) 1st hour, Visual Analogue Scale (VAS) of pain, Health Assessm…
FRI0030 Anti-TNF-α Antibody Targeted To Inflamed Synovial Tissue for The Treatment of Rheumatoid Arthritis
2016
Background TNF-α neutralizing molecules represent one of the most efficient therapeutic approaches to control inflammation in rheumatoid arthritis (RA). The widespread distribution in the body induces the inhibition of TNF-α in all the tissues, requesting the use of high dose of this expensive drug. Another problem that has not yet been solved in the management of RA patients is how to reduce and possibly avoid the side effects, particularly the increased risk of common and opportunistic infections, which may be associated with long-term administration of these therapeutic drugs. Objectives The aim of the present investigation was to show that a recombinant protein obtained by fusing a syno…
Treatment approaches to patients with multiple sclerosis and coexisting autoimmune disorders.
2021
The past decades have yielded major therapeutic advances in many autoimmune conditions – such as multiple sclerosis (MS) – and thus ushered in a new era of more targeted and increasingly potent immunotherapies. Yet this growing arsenal of therapeutic immune interventions has also rendered therapy much more challenging for the attending physician, especially when treating patients with more than one autoimmune condition. Importantly, some therapeutic strategies are either approved for several autoimmune disorders or may be repurposed for other conditions, therefore opening new curative possibilities in related fields. In this article, we especially focus on frequent and therapeutically rele…
Rho GTPases Are Involved in the Regulation of NF-κB by Genotoxic Stress
2001
A common cellular response to genotoxic agents and inflammatory cytokines is the activation of NF-kappaB. Here, we addressed the question of whether small GTPases of the Rho family are involved in the stimulation of NF-kappaB signaling by genotoxic agents or TNFalpha in HeLa cells. Inhibition of isoprenylation of Rho proteins by use of the HMG-CoA reductase inhibitor lovastatin attenuated UV-, doxorubicin-, and TNFalpha-induced degradation of IkappaBalpha as well as drug-stimulated DNA binding activity of NF-kappaB. Furthermore, NF-kappaB-regulated gene expression stimulated by either UV irradiation or treatment with TNFalpha was abrogated by lovastatin pretreatment. This indicates that iso…
A novel microtubule de-stabilizing complementarity-determining region C36L1 peptide displays antitumor activity against melanoma in vitro and in vivo
2015
AbstractShort peptide sequences from complementarity-determining regions (CDRs) of different immunoglobulins may exert anti-infective, immunomodulatory and antitumor activities regardless of the specificity of the original monoclonal antibody (mAb). In this sense, they resemble early molecules of innate immunity. C36L1 was identified as a bioactive light-chain CDR1 peptide by screening 19 conserved CDR sequences targeting murine B16F10-Nex2 melanoma. The 17-amino acid peptide is readily taken up by melanoma cells and acts on microtubules causing depolymerization, stress of the endoplasmic reticulum and intrinsic apoptosis. At low concentrations, C36L1 inhibited migration, invasion and proli…
Lovastatin inhibits Rho-regulated expression of E-selectin by TNFalpha and attenuates tumor cell adhesion.
2003
E-selectin mediated cell-cell adhesion plays an important role in inflammatory processes and extravasation of tumor cells. Tumor necrosis factor-alpha (TNF-alpha) induces E-selectin gene and protein expression in primary human endothelial cells (HUVEC) and in an endothelial cell line (EA.hy-926). As shown by ELISA and FACS analyses, HMG-CoA reductase inhibitors (e.g., lovastatin) impair the TNF-alpha stimulated increase in E-selectin protein expression. Similar results were obtained for E-selectin mRNA expression and promoter activity, indicating that the effect of lovastatin is based on inhibition of gene expression. The effective inhibitory concentration of lovastatin was in a physiologic…
Detection of natural killer T cells in mice infected with Rickettsia conorii.
2013
Little information is available regarding the role of natural killer T (NKT) cells during the early stage of Rickettsia conorii infection. Herein, C3H/HeN mice were infected with the Malish 7 strain of R. conorii. Splenocytes from these mice were analysed in the early stage of the infection by flow cytometry and compared with uninfected controls. Our results showed an increase in NKT cells in infected mice. Additionally, NKT interleukin (IL)-17(+) cells increased three days after infection, together with a concurrent decrease in the relative amount of NKT interferon (IFN)-γ(+) cells. We also confirmed a higher amount of NK IFN-γ(+) cells in infected mice. Taken together, our data showed tha…