1,721,243 research outputs found
SMAD4 gene mutation and risk of aortic dilation: Lessons from hereditary hemorrhagic telangiectasia
No full textLarge-scale use of hydroxychloroquine for COVID-19 confirms safety, if not effectiveness
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Effects of physical exercise and body weight on disease-specific outcomes of people with rheumatic and musculoskeletal diseases (rmds): systematic reviews and meta-analyses informing the 2021 eular recommendations for lifestyle improvements in people with
Full text linkThis work was funded by the European League Against Rheumatism.
SMMV and JMG are supported by Versus Arthritis (grant number 21755) and the
NIHR Manchester Biomedical Research Centre. The views expressed are those of
the author(s) and not necessarily those of the NHS, the NIHR or the Department of
Health.Gwinnutt J.M., Wieczorek M., Cavalli G., Balanescu A., Bischoff-Ferrari H.A., Boonen A., De Souza S., De Thurah A., Dorner T.E., Moe R.H., Putrik P., Rodríguez-Carrio J., Silva-Fernández L., Stamm T., Walker-Bone K., Welling J., Zlatković-Švenda M.I., Guillemin F., Verstappen S.M.M
Anakinra therapy for non-cancer inflammatory diseases
No full textInterleukin-1 (IL-1) is the prototypical inflammatory cytokine: two distinct ligands (IL-1α and IL-1β) bind the IL-1 type 1 receptor (IL-1R1) and induce a myriad of secondary inflammatory mediators, including prostaglandins, cytokines, and chemokines. IL-1α is constitutively present in endothelial and epithelial cells, whereas IL-1β is inducible in myeloid cells and released following cleavage by caspase-1. Over the past 30 years, IL-1-mediated inflammation has been established in a broad spectrum of diseases, ranging from rare autoinflammatory diseases to common conditions such as gout and rheumatoid arthritis (RA), type 2 diabetes, atherosclerosis, and acute myocardial infarction. Blocking IL-1 entered the clinical arena with anakinra, the recombinant form of the naturally occurring IL-1 receptor antagonist (IL-1Ra); IL-1Ra prevents the binding of IL-1α as well as IL-1β to IL-1R1. Quenching IL-1-mediated inflammation prevents the detrimental consequences of tissue damage and organ dysfunction. Although anakinra is presently approved for the treatment of RA and cryopyrin-associated periodic syndromes, off-label use of anakinra far exceeds its approved indications. Dosing of 100 mg of anakinra subcutaneously provides clinically evident benefits within days and for some diseases, anakinra has been used daily for over 12 years. Compared to other biologics, anakinra has an unparalleled record of safety: opportunistic infections, particularly Mycobacterium tuberculosis, are rare even in populations at risk for reactivation of latent infections. Because of this excellent safety profile and relative short duration of action, anakinra can also be used as a diagnostic tool for undefined diseases mediated by IL-1. Although anakinra is presently in clinical trials to treat cancer, this review focuses on anakinra treatment of acute as well as chronic inflammatory diseases
Suppression of inflammation and acquired immunity by IL-37
No full textIL-37 is a unique member of the IL-1 family of cytokines, which functions as a natural suppressor of inflammatory and immune responses. Immune and non-immune cells produce IL-37 precursor following pro-inflammatory stimuli. Following activating cleavage by caspase-1, mature IL-37 translocates to the nucleus, where it suppresses transcription of pro-inflammatory genes. Both precursor and mature IL-37 are also secreted in the extracellular space, where they bind IL-18Rα and recruit the IL-1R8 (formerly TIR8 or SIGIRR), which transduces anti-inflammatory signals by suppressing NF-kB and MAPK and by activating Mer-PTEN-DOK pathways. During inflammation, IL-37 restores the metabolism of the cell by reducing succinate, inhibiting mTOR, and activating AMPK. Transgenic mice expressing human IL-37 and wild type mice treated with recombinant human IL-37 are protected from several experimental models of inflammation, including endotoxin shock, colitis, lung and spinal cord injury, coronary artery disease, arthritis and inflammation-induced fatigue, while also exhibiting reduced adaptive immune responses. In humans, IL-37 likely functions to limit excessive inflammation: accordingly, IL-37 levels are abnormal in patients with inflammatory and autoimmune diseases. In this review, we provide an overview of the discovery and biology of IL-37, and discuss the potential for development of this cytokine as a therapeutic agent
Treating rheumatological diseases and co-morbidities with interleukin-1 blocking therapies
No full textThe inflammatory cytokines IL-1α and IL-1β orchestrate local and systemic inflammatory responses underlying a broad spectrum of diseases. Three agents for reducing IL-1 activities are currently available. Anakinra is a recombinant form of the naturally occurring IL-1 receptor antagonist. Anakinra binds to the IL-1 receptor and prevents the activity of IL-1α and IL-1β. The soluble decoy receptor rilonacept and the neutralizing mAb canakinumab block IL-1β. A mAb directed against the IL-1 receptor and a neutralizing anti-human IL-1α are in clinical trials. The availability of therapies specifically targeting IL-1 unveiled the pathological role of IL-1-mediated inflammation in a broadening list of diseases. Conditions effectively treated with agents blocking IL-1 range from classic rheumatic diseases, such as RA and gout, to autoinflammatory syndromes, such as systemic JIA and FMF. However, IL-1 antagonism is also effective against highly prevalent inflammatory diseases, namely cardiovascular diseases and type 2 diabetes, conditions that are frequently encountered as co-morbidities in patients with rheumatic diseases. Thereby, IL-1 inhibition has the potential to lift the burden of disease for patients with rheumatic conditions, but also to provide clinical benefits beyond the efficacy on osteoarticular manifestations
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
The choice of early treatment and the impact of future relapses in adult onset Still's disease
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