B cell autoimmunity and bone damage in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic immune-inflammatory disease associated with significant bone damage. Pathological bone remodeling in RA is primarily driven by persistent inflammation. Indeed, pro-inflammatory cytokines stimulate the differentiation of bone-resorbing osteoclasts and, in parallel, suppress osteoblast function, resulting in net loss of bone. Abating disease activity thus remains the major goal of any treatment strategy in patients with RA. Autoantibody-positive patients, however, often show a rapidly progressive destructive course of the disease, disproportionate to the level of inflammation. The epidemiological association between RA-specific autoantibodies, in particular anti-citrullinated protein autoantibodies, and poor structural outcomes has recently found mechanistic explanation in the multiple roles that B cells play in bone remodeling. In this review, we will summarize the substantial progress that has been made in deciphering how B cells and autoantibodies negatively impact on bone in the course of RA, through both inflammation-dependent and independent mechanisms

L’utilizzo delle protesi endoscopiche nella patologia dell’apparato digerente

L’utilizzo di protesi ad introduzione per via endoscopica per patologie dell’apparato digerente sia benigne che maligne ha avuto negli ultimi anni un considerevole sviluppo. Il posizionamento delle endoprotesi è ben tollerato dai pazienti, non necessita di anestesia e comporta rischi relativamente minimi. Le nuove protesi metalliche autoespansibili permettono di risolvere stenosi anche molto serrate senza quasi mai necessità di dilatazione, con riduzione dei rischi che da questa derivano. Viene riportata una revisione dell’esperienza di protesizzazione per patologie dell’apparato digerente e vengono discussi le indicazioni, i limiti e le complicanze, sulla scorta dei dati dalla letteratura internazionale

The gamma-ray burst monitor for Lobster-ISS

Lobster-ISS is an X-ray all-sky monitor experiment selected by ESA two years ago for a Phase A study (now almost completed) for a future flight (2009) aboard the Columbus Exposed Payload Facility of the International Space Station. The main instrument, based on MCP optics with Lobster-eye geometry, has an energy passband from 0.1 to 3.5 keV, an unprecedented daily sensitivity of 2x10^{-12} erg cm^{-2}s$^{-1}, and it is capable to scan, during each orbit, the entire sky with an angular resolution of 4--6 arcmin. This X-ray telescope is flanked by a Gamma Ray Burst Monitor, with the minimum requirement of recognizing true GRBs from other transient events. In this paper we describe the GRBM. In addition to the minimum requirement, the instrument proposed is capable to roughly localize GRBs which occur in the Lobster FOV (162x22.5 degrees) and to significantly extend the scientific capabilities of the main instrument for the study of GRBs and X-ray transients. The combination of the two instruments will allow an unprecedented spectral coverage (from 0.1 up to 300/700 keV) for a sensitive study of the GRB prompt emission in the passband where GRBs and X-Ray Flashes emit most of their energy. The low-energy spectral band (0.1-10 keV) is of key importance for the study of the GRB environment and the search of transient absorption and emission features from GRBs, both goals being crucial for unveiling the GRB phenomenon. The entire energy band of Lobster-ISS is not covered by either the Swift satellite or other GRB missions foreseen in the next decade.Comment: 6 pages, 4 figures. Paper presented at the COSPAR 2004 General Assembly (Paris), accepted for publication in Advances in Space Research in June 2005 and available on-line at the Journal site (http://www.sciencedirect.com/science/journal/02731177), section "Articles in press

Pro-oxidant effects of Verbascoside, a bioactive compound from olive oil mill wastewater, on in vitro developmental potential of ovine prepubertal oocytes and bioenergetic/oxidative stress parameters of fresh and vitrified oocytes

Verbascoside (VB) is a bioactive polyphenol from olive oil mill wastewater with known antioxidant activity. Oxidative stress is an emerging problem in assisted reproductive technology (ART). Juvenile ART is a promising topic because, in farm animals, it reduces the generation gap and, in human reproductive medicine, it helps to overcome premature ovarian failure. The aim of this study was to test the effects of VB on the developmental competence of ovine prepubertal oocytes and the bioenergetic/oxidative stress status of fresh and vitrified oocytes. In fresh oocytes, VB exerted prooxidant short-term effects, that is, catalase activity increase and uncoupled increases of mitochondria and reactive oxygen species (ROS) fluorescence signals, and long-term effects, that is, reduced blastocyst formation rate. In vitrified oocytes, VB increased ROS levels. Prooxidant VB effects in ovine prepubertal oocytes could be related to higher VB accumulation, which was found as almost one thousand times higher than that reported in other cell systems in previous studies. Also, long exposure times of oocytes to VB, throughout the duration of in vitro maturation culture, may have contributed to significant increase of oocyte oxidation. Further studies are needed to identify lower concentrations and/or shorter exposure times to figure out VB antioxidant effects in juvenile ARTs

Anti-citrullinated protein antibodies and high levels of rheumatoid factor are associated with systemic bone loss in patients with early untreated rheumatoid arthritis

BACKGROUND: Autoantibodies such as anti-citrullinated protein antibodies (ACPA) are major risk factors for articular bone destruction from the earliest phases of rheumatoid arthritis (RA). The aim of the current study was to determine whether RA-associated autoantibodies also impact on systemic bone loss in patients with early disease. METHODS: Systemic bone mineral density (BMD) was measured in the lumbar spine and the hip in 155 consecutive treatment-na\uefve patients with early RA (median symptom duration 13 weeks). Demographic and disease-specific parameters, including clinical disease activity, ultrasonographic (US) examination of the hands and wrists, radiographic scoring of joint damage, ACPA and rheumatoid factor (RF) levels were recorded from all patients. Reduced BMD was defined as Z score\u2009 64\u2009-1 SD and analysed in relation to disease-related characteristics and autoantibody subgroups. RESULTS: Reduced BMD was found in 25.5 % of the patients in the spine and 19.4 % in the hip. Symptom duration, clinical and US disease activity, functional disability and radiographic damage did not significantly impact on spine and hip BMD loss in regression analyses adjusted for possible confounders (age, gender, menopausal status, current smoking, body mass index). In contrast, ACPA positivity (at any level) negatively affected the spine Z-score (adjusted OR (95 % CI) 2.76 (1.19 to 6.42)); the hip Z score was affected by high titres only (adjusted OR (95 % CI) 2.96 (1.15 to 7.66)). The association of ACPA with reduced BMD in the spine was confirmed even at low levels of RF (adjusted OR (95 % CI) 2.65 (1.01 to 7.24)), but was further increased by concomitant high RF (adjusted OR (95 % CI) 3.38 (1.11 to 10.34)). In contrast, Z scores in the hip were significantly reduced only in association with high ACPA and RF (adjusted OR (95 % CI) 4.96 (1.48 to 16.64)). CONCLUSIONS: Systemic BMD in patients with early RA is reduced in relation with ACPA positivity and high RF levels. This finding supports the notion that RA-associated autoimmunity may have a direct causative role in bone remodeling

Vitamin D 25OH Deficiency and Mortality in Moderate to Severe COVID-19: A Multi-Center Prospective Observational Study

Introduction: Several studies and meta-analyses suggested the role of vitamin D 25OH in preventing severe forms of coronavirus disease 2019 (COVID-19). However, the evidence on the clinical benefits of vitamin D 25OH adequacy in patients hospitalized for COVID-19 remain conflicting and speculative. We aimed to investigate the association between vitamin D 25OH serum levels and mortality in hospitalized patients with moderate to severe COVID-19. Method: This prospective observational multicentre study included 361 consecutive patients with moderate to severe COVID-19 admitted to the Italian hospitals involved in the NUTRI-COVID19 trial from March to August 2020. For each patient, serum vitamin D 25OH levels were assessed 48 h since admission and classified as deficient (<20 ng/mL) or adequate (≥20 ng/mL). We built a propensity score for low/adequate vitamin D 25OH levels to balance the clinical and demographic properties of the cohort, which resulted in 261 patients with good common support used for the survival analysis. Results: Two Hundred-seventy-seven (77%) of the 361 enrolled patients (207 [57%] males, median age 73 ± 15.6 years) had vitamin D 25OH deficiency. Fifty-two (20%) of the 261 matched patients died during the hospital stay, corresponding to a hazard ratio of 1.18 for vitamin D 25OH deficiency (95% confidence interval: 0.86–1.62; p = 0.29). Discussion: The prevalence of vitamin D 25OH deficiency was confirmed to be very high in hospitalized patients with COVID-19. The use of a propensity score demonstrate an absence of significant association between vitamin D deficiency and mortality in hospitalized patients