RESUMO
The aim of this study was to investigate the effects of the lipid mediator Resolvin D1 in experimental keratitis. C57BL/6J mice were injected with lipopolysaccharide (2 µg/eye), and after 24 hours, the corneal damage was assessed. Clinical score was quantified, and corneal inflammatory biomarkers were detected by immunohistochemistry. A robust accumulation of sub-epithelial macrophages and polymorphonuclear leucocytes, chemokine (C-X-C motif) ligand 1 (also known as keratinocyte-derived chemokine), interleukin-10 and promoters of apoptosis was also observed in lipopolysaccharide-treated mice. Formyl peptide receptor 2 corneal expression was also assessed. The corneal stroma treated with lipopolysaccharide was characterized by presence of macrophages of M1-like subtype and immature fibroblastic cells, marked with Ki67, not fully differentiated in fibroblasts. Indeed, the staining of the cornea with anti-vimentin antibodies, a marker of differentiated myofibroblasts, was very faint. Resolvin D1 attenuated all the inflammatory parameters assessed in the present study, except for IL-10. In conclusion, the data presented here seem to be consistent with the hypothesis that Resolvin D1 protected the cornea from the lipopolysaccharide-induced keratitis by acting on several inflammatory components of this damage, pivoted by Formyl peptide receptor 2 (FPR2) activation and macrophages-leucocytes activity.
Assuntos
Substância Própria/metabolismo , Ácidos Docosa-Hexaenoicos/metabolismo , Inflamação/metabolismo , Ceratite/tratamento farmacológico , Animais , Apoptose , Conexina 43/metabolismo , Córnea/efeitos dos fármacos , Modelos Animais de Doenças , Fibroblastos/metabolismo , Imuno-Histoquímica , Interleucina-10/metabolismo , Ceratite/induzido quimicamente , Ceratite/metabolismo , Antígeno Ki-67/metabolismo , Leucócitos/metabolismo , Lipopolissacarídeos , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fenótipo , Vimentina/metabolismoRESUMO
Introduction: In recent years, a significant decrease in the number of clinical trials was observed among EU countries. This decline could be attributed to several factors, including the financial crisis of EU countries, the requirements introduced by the Directive 2001/20/EC and the increased market attractiveness of not EU countries.Areas covered: The EU Clinical Trials Regulation (CTR) 536/2014 was adopted in April 2014 by the European Parliament. The main changes arising from the CTR, including but not limited to the activation of a new EU portal, the potentiation of the already existing EU database and the requirement to provide plain language summaries of clinical trials, are aimed to improve the competitiveness of Europe in clinical research scenario and promote a faster approval of clinical trials. In this review, data related to the CTR 536/2014 and its potential implications in terms of transparency are based on pertinent papers that were retrieved by the PubMed database and the internet.Expert opinion: The full implementation of the CTR 536/2014 requires close cooperation between EU member states and regulatory agencies. Some aspects should be carefully considered such as the interaction with ethics committees, the insurance coverage and the protection of personal data issues.
