Identification of a cytokine network sustaining neutrophil and Th17 activation in untreated early rheumatoid arthritis

© 2010 Cascão et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by sustained synovitis. Recently, several studies have proposed neutrophils and Th17 cells as key players in the onset and perpetuation of this disease. The main goal of this work was to determine whether cytokines driving neutrophil and Th17 activation are dysregulated in very early rheumatoid arthritis patients with less than 6 weeks of disease duration and before treatment (VERA). Methods: Cytokines related to neutrophil and Th17 activation were quantified in the serum of VERA and established RA patients and compared with other very early arthritis (VEA) and healthy controls. Synovial fluid (SF) from RA and osteoarthritis (OA) patients was also analyzed. Results: VERA patients had increased serum levels of cytokines promoting Th17 polarization (IL-1b and IL-6), as well as IL-8 and Th17-derived cytokines (IL-17A and IL-22) known to induce neutrophil-mediated inflammation. In established RA this pattern is more evident within the SF. Early treatment with methotrexate or corticosteroids led to clinical improvement but without an impact on the cytokine pattern. Conclusions: VERA patients already display increased levels of cytokines related with Th17 polarization and neutrophil recruitment and activation, a dysregulation also found in SF of established RA. 0 Thus, our data suggest that a cytokine-milieu favoring Th17 and neutrophil activity is an early event in RA pathogenesis.This work was supported by a grant from Sociedade Portuguesa de Reumatologia/Schering-Plough 2005. RAM and RC were funded by Fundação para a Ciência e a Tecnologia (FCT) SFRH/BD/30247/2006 and SFRH/BD/40513/2007, respectively. MMS-C was funded by Marie Curie Intra-European Fellowship PERG-2008-239422 and a EULAR Young Investigator Award

Determinants of emergency contraception non-use among women in unplanned or ambivalent pregnancies

Objective To analyze the determinants of emergency contraception non-use among women in unplanned and ambivalent pregnancies. Method Cross-sectional study with a probabilistic sample of 366 pregnant women from 12 primary health care units in the city of São Paulo, Brazil. A multinomial logistic regression was performed, comparing three groups: women who used emergency contraception to prevent ongoing pregnancies (reference); women who made no use of emergency contraception, but used other contraceptive methods; and women who made no use of any contraceptive methods at all. Results Cohabitation with a partner was the common determinant of emergency contraception non-use. No pregnancy risk awareness, ambivalent pregnancies and no previous use of emergency contraception also contributed to emergency contraception non-use. Conclusion Apart from what is pointed out in the literature, knowledge of emergency contraception and the fertile period were not associated to its use

Recent advances in ankylosing spondylitis: understanding the disease and management

The term spondyloarthritis refers to a group of immune-mediated diseases characterised by inflammation of the axial skeleton, peripheral joints, and entheses. Ankylosing spondylitis (AS) is the most common and characteristic of these entities and even though it was first described over two centuries ago, the understanding of the underlying disease mechanism remains incomplete. It is known that around 40% of patients with AS have subclinical bowel inflammation, suggesting that the origin of the disease could be in the gut. Also, more genes and new molecules have demonstrated a role in the pathogenesis of AS. In this review, we analyse the latest therapies for spondyloarthritis and the most relevant discoveries over the last three years, together with their implications for different aspects of the disease

Thermoanalytical study of nimesulide and their recrystallization products obtained from solutions of several alcohols

Thermogravimetry, differential scanning calorimetry, and vibrational infrared spectroscopy were used to study nimesulide and its recrystallization products that were obtained from solutions of several alcohols. The thermoanalytical measurements were performed in both air and nitrogen atmospheres and the results suggest that, under the experimental conditions used in this paper, it was possible to obtain neither polymorphic nor pseudopolymorphic forms of this drug. In this investigation, quantum chemical approach methods were used to determine the molecular structures using the Becke three-parameter hybrid method and the Lee-Yang-Parr correlation functional. The performed molecular calculations were done with the Gaussian 09 routine and the theoretical calculation results were correlated with the experimental IR vibrational spectrum. © 2013 Akadémiai Kiadó, Budapest, Hungary

Thermal behavior of some antihistamines

Thermogravimetry (TG), differential scanning calorimetry (DSC), polarized light thermal microscopy (PLTM), as well as X-ray powder diffraction (XRD) and Fourier transformed infrared spectroscopy (FTIR) were used to study the thermal behavior and the chemical structure of cimetidine, famotidine, ranitidine-HCl, and nizatidine. The TG-DSC curves show that the famotidine and ranitidine-HCl suffer decomposition during melting and they are thermally less stable in comparison with cimetidine and nizatidine, the latter being the most stable of all the drugs studied in this study. The DSC curves of famotidine and ranitidine-HCl show exothermic peaks immediately after the melting, confirming the occurrence of thermal decomposition. The DSC curves also show that the cimetidine and nizatidine have some thermal stability after melting. The thermal events shown in the PLTM images are consistent with the results shown in the TG-DSC and DSC curves. The XRD patterns show that the cimetidine and famotidine are less crystalline compared with ranitidine-HCl and nizatidine. The theoretical FTIR bands are in agreement with those obtained experimentally, and in some cases, no difference is observed between the theoretical and experimental values, even being identical in one of the cases. © 2012 Akadémiai Kiadó, Budapest, Hungary