2,083 research outputs found
Clinical utility of the oral JAK inhibitor tofacitinib in the treatment of rheumatoid arthritis
No full textMaurizio Cutolo, Marianna Meroni Research Laboratories and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genova, Genova, Italy Abstract: Immune/inflammatory cells act in rheumatoid arthritis (RA)-affected patients by synthesizing several inflammatory mediators, including cytokines that initiate intracellular signaling. Recently, small molecule inhibitors of transduction and transcription signals that influence the intracellular pathways (such as the Janus kinase [JAK] family of tyrosine kinases) have been tested for RA treatment. Four members of the JAK family are known: JAK1, JAK2, JAK3, and TyK2. JAK1/JAK3 constitutively binds to the cytoplasmic portion of the cytokine receptor – the common gamma chain – that represents a common subunit of several cytokines involved in T-cell and natural killer cell development, as well as in B-cell activation. Tofacitinib is an oral JAK inhibitor that is now available and effective in RA treatment, as shown in multiple Phase II and Phase III clinical trials. However, long-term safety data and comparisons with other disease-modifying antirheumatic drugs and small molecule inhibitors are necessary to better determine the role of tofacitinib in RA. Keywords: Janus kinase inhibitors, tofacitinib, rheumatoid arthritis, kinases, small molecules inhibitors, intracellular signalin
RELATIONSHIPS BETWEEN BONE LOSS AND MICROVASCULAR DAMAGE IN PATIENTS WITH SYSTEMIC SCLEROSIS
No full text[FRI0325] RELATIONSHIPS BETWEEN BONE LOSS AND MICROVASCULAR DAMAGE IN PATIENTS WITH SYSTEMIC SCLEROSIS
Authors: B. Seriolo, C. Pizzorni, A. Casabella, G. Zampogna, A. Sulli, M. Cutolo
Session Info: Scleroderma, myositis and related syndromes
Year: 201
Cutolo, Alessandro. L'« Officium Beatœ Mariœ Virginis » donato da Ludovico il Mauro a Carlo VIII re di Francia Cutolo, Alessandro. Romanzi Cavallereschi in Prosa e in Rima del Fondo Casteglioni presso la Biblioteca Braidense di Milano
No full textDelaissé L.-M.-J. Cutolo, Alessandro. L'« Officium Beatœ Mariœ Virginis » donato da Ludovico il Mauro a Carlo VIII re di Francia Cutolo, Alessandro. Romanzi Cavallereschi in Prosa e in Rima del Fondo Casteglioni presso la Biblioteca Braidense di Milano. In: Scriptorium, Tome 1 n°2, 1946. p. 355
Cutolo, Alessandro. L'« Officium Beatœ Mariœ Virginis » donato da Ludovico il Mauro a Carlo VIII re di Francia Cutolo, Alessandro. Romanzi Cavallereschi in Prosa e in Rima del Fondo Casteglioni presso la Biblioteca Braidense di Milano
No full textDelaissé L.-M.-J. Cutolo, Alessandro. L'« Officium Beatœ Mariœ Virginis » donato da Ludovico il Mauro a Carlo VIII re di Francia Cutolo, Alessandro. Romanzi Cavallereschi in Prosa e in Rima del Fondo Casteglioni presso la Biblioteca Braidense di Milano. In: Scriptorium, Tome 1 n°2, 1946. p. 355
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
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