1,721,825 research outputs found
Circadian rhythms and rheumatoid arthritis
No full textCircadian rhythms (Nobel prize for Medicine 2017) regulate, under action of biological clocks located
both at the level of central nervous system and inside peripheral cells, several daily activities, embracing
sleep, feeding times, energy metabolism, endocrine and immune functions with related pathological
conditions, including rheumatoid arthritis (RA).
In RA the circadian rhythms impact on cellular functions, involving night synthesis and release of
pro-inflammatory cytokines and chemokines, cell migration to inflamed tissues, phagocytosis, proliferative cell response and all are peaking at late night. In chronic inflammatory conditions such as RA,
the amplitude of the circadian rhythm of the anti-inflammatory endogenous cortisol availability is not
increased as expected and requested, which indicate a reduced night cortisol secretion under the adrenal
chronic stress induced by the disease. Therefore, the prevention/treatment of the immune cell night
hyperactivity, with related flare of cytokine synthesis and morning RA clinical symptoms, has been shown
more effective when the availability of the exogenous glucocorticoids is obtained in the middle of the
night (night release). The impressive positive results observed in RA patients treated with modifiednight release prednisone with a low-dose chronotherapy, seem applicable even for other agents such
as conventional NSAIDs and DMARDs, including the positive experimental and clinical results obtained
by the night time daily administration of methotrexate. Interestingly, a very recent study showed that
methotrexate upregulates important cell circadian genes, resulting in induction of apoptosis in synovial fibroblasts. The link between the circadian rhythms of the disease and the chronotherapy of RA is
promisin
Glucocorticoids and chronic inflammation.
No full textGlucocorticoids are steroid hormones that once bound to their receptor interact with the DNA binding domain. Almost 1000–2000 genes are sensitive to their effects, including immune/inflammatory response genes. However, their role in pathophysiology and therapy is still debated. We performed a literature survey using the key words glucocorticoids, inflammation, autoimmune disease, rheumatology and adrenal glands in order to define important targets for this review on glucocorticoids. Considering endogenous/exogenous glucocorticoids in chronic inflammatory diseases brought up five major points for discussion: inadequately low production of endogenous cortisol relative to systemic inflammation (the disproportion principle); changes of the systemic and local cortisol-to-cortisone shuttle (reactivation and degradation of cortisol); inflammation-induced glucocorticoid resistance; highlights of present glucocorticoid therapy; and the role of circadian rhythms in action of cortisol. Much of this information becomes understandable in the context of neurohormonal energy regulation as recently summarized. The optimization of long-term low-dose glucocorticoid therapy in chronic inflammatory diseases arises from the understanding of the above mentioned aspects. Since glucocorticoid resistance is a consequence of inflammation, adequate anti-inflammatory therapy is mandatory
Complex role of oestrogens in the risk and severity of rheumatoid arthritis in menopause
No full textClinical practice guidelines: the first year of activity of the European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases (ERN ReCONNET).
No full textTesting the anti-osteoclastic function of biologic DMARDs
No full textA variety of biologic DMARDs now exist for the treatment of rheumatoid arthritis, but we don’t really know how these drugs function in vivo. Can time-lapse intravital imaging distinguish the modes of action of DMARDs by comparing response to joint destruction in mouse models of arthritis
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