BACKGROUND AND PURPOSEEndogenous glucocorticoids are pro-resolving mediators, an example of which is the endogenous glucocorticoid-regulated protein annexin A1 (ANXA1). Because silicosis is an occupational lung disease characterized by unabated inflammation and fibrosis, in this study we tested the therapeutic properties of the N-terminal ANXA1-derived peptide annexin 1-(2-26) (Ac2-26) on experimental silicosis. EXPERIMENTAL APPROACHSwiss-Webster mice were administered silica particles intranasally and were subsequently treated with intranasal peptide Ac2-26 (200 μg per mouse) or dexamethasone (25 μg per mouse) for 7 days, starting 6 h post-challenge. Ac2-26 abolished the leukocyte infiltration, collagen deposition, granuloma formation and generation of pro-inflammatory cytokines evoked by silica; these variables were only partially inhibited by dexamethasone. KEY RESULTSA clear exacerbation of the silica-induced pathological changes was observed in ANXA1 knockout mice as compared with their wild-type (WT) littermate controls. Incubation of lung fibroblasts from WT mice with Ac2-26 in vitro reduced IL-13 or TGF-β-induced production of CCL2 (MCP-1) and collagen, but this peptide did not affect the production of CCL2 (MCP-1) by stimulated fibroblasts from formyl peptide receptor type 1 (FPR1) knockout mice. Ac2-26 also inhibited the production of CCL2 (MCP-1) from fibroblasts of FPR2 knockout mice. CONCLUSIONS AND IMPLICATIONSCollectively, our findings reveal novel protective properties of the ANXA1 derived peptide Ac2-26 on the inflammatory and fibrotic responses induced by silica, and suggest that ANXA1 mimetic agents might be a promising strategy as innovative anti-fibrotic approaches for the treatment of silicosis. IntroductionSilicosis is a lung occupational disease caused by inhalation of free crystalline silica particles over a prolonged period of time. This disease mainly affects workers in the ceramic industry, glass manufacturing, sandblasting, mining, quarrying and civil construction (Leung et al., 2012;Singer et al., 2012). Silicosis is a problem worldwide, but it is prevalent in countries of low and middle income. China had more than 500 000 cases recorded between 1991 and 1995, and 6000 new cases and more than 24 000 deaths are reported annually (Leung et al., 2012). In Brazil more than 4500 workers were reported to have silicosis between 1978 and 1998, especially in the gold-mining area in Minas Gerais (Carneiro et al., 2006). The irritative action of silica in the lungs results in the formation of nodular lesions, which may coalesce resulting in massive areas of fibrous tissue and reduction of lung elasticity (Davis, 1986). Because of its surface properties, crystalline silica leads to activation of alveolar macrophages [acting on 'scavenger' receptors such as the MARCO (macrophage receptor with collagenous structure)], epithelial cells and fibroblasts (Mossman and Churg, 1998;Fubini and Hubbard, 2003;Huaux, 2007). The granulomatous inflammation induced by silica is characterized by the accumulati...

Selective platelet-activating factor (PAF) antagonists and autodesensitization to this lipid were used to investigate the role of PAF in antigen-induced pleurisy in the rat. Pleural inflammation was triggered by the intrathoracic (i.t.) injection of ovalbumin (12 micrograms/cavity) into animals actively sensitized 14 days before. Successive daily i.t. injections of PAF (1 microgram/cavity) led to selective autodesensitization, which was apparent after the third injection and maximal after the fifth. The PAF antagonists BN 52021 and WEB 2086 inhibited the late pleural eosinophil accumulation caused by antigen but, as also noted with WEB 2170, failed to modify the early antigen-induced plasma exudation and leukocyte infiltration. In contrast to the antagonists, desensitization to PAF was clearly effective against these early alterations. To further investigate this discrepancy, the antigenic challenge was performed 24 h after a single prestimulation with PAF, when sensitivity to the lipid was still intact. Under this condition, plasma exudation and cellular influx triggered by the antigen were also abrogated, indicating that this protective effect was accounted for by a mechanism other than refractoriness to PAF. Because 24 h after PAF injection only eosinophil counts remained elevated, an alternative eosinophilotactic substance was used to further study the mechanism of PAF versus antigen-induced pleural inflammation. Prior treatment with the peptide Ala-Gly-Ser-Glu (ECF-A, 20 micrograms/cavity) also inhibited the allergic pleurisy, whereas the noneosinophilotactic substances histamine (200 micrograms/cavity) and serotonin (100 micrograms/cavity) were inactive. Furthermore, drugs that share the ability to impair PAF-induced eosinophilia, including azelastine and cetirizine, prevented the inhibitory effect of PAF on the antigen-induced pleurisy. These findings suggest that PAF may account for the late eosinophilia, but not for the acute phase of the rat allergic pleurisy, which is clearly attenuated by PAF or ECF-A pretreatment.

The symptoms' heterogeneity of people with ASD requires that therapeutic and educational interventions be case-specific. In Brazil, the government's guidelines aim the educational inclusion of this population in regular school with technology support. In this scenario, it is relevant a national scientific production mapping that have been addressing "Autism, Education and Technology" for compiling information aiming a research collaboration network. Therefore, a literature review was conducted, contemplating 33 articles. A prevalence of educational software solutions for literacy of children with ASD was identified, and these studies were published more frequently in Alagoas and Rio Grande do Sul.

Objective: To analyze self-care and knowledge in patients with heart failure who were monitored telephonically, and to analyze the correlation of knowledge with self-care. Methods: It was a randomized clinical trial, performed in a specialized clinic from April of 2015 to December of 2015. Thirty-six patients were monitored and randomized, with 17 in the control group and 19 in the intervention group. Both groups participated in the conventional monitoring, which included three visits (initial, second and fourth month); the intervention group was associated with telephone support by means of a standardized guide. The Knowledge and Self-Care Questionnaires were used to evaluate the primary and secondary outcomes. Results: Difference in knowledge (12.7±1.7 vs. 10.8±2.2, p=0.009) and self-care (25.4±6.6 vs. 29.5±4.8, p=0. 04) were identified in the fourth month; and there was a negative correlation between knowledge and self-care scores in the second month (r =-0.48; p=0.03). Conclusion:The conventional management combined with telephone monitoring was effective in the 4 th month with improved knowledge and self-care of patients with heart failure and a significant correlation of these outcomes in the second month. ResumoObjetivo: Analisar o autocuidado e o conhecimento em pacientes com insuficiência cardíaca monitorados por contato telefônico e analisar a correlação do conhecimento com o autocuidado. Métodos: Ensaio clínico randomizado, realizado em uma clínica especializada, no período de abril de 2015 a dezembro de 2015. Foram monitorados e randomizados 36 pacientes no Grupo Controle (17) ou no Grupo Intervenção (19). Ambos os grupos participaram do monitoramento convencional, compreendendo três atendimentos (Basal; 2º mês; 4º mês); no Grupo Intervenção houve associação do monitoramento telefônico por meio de um guia padronizado. Foram utilizados os Questionários de Conhecimento e de Autocuidado para avaliação dos desfechos primários e secundários. Resultados: Houve diferença no conhecimento (12,7±1,7 vs. 10,8±2,2; p=0,009) e autocuidado (25,4±6,6 vs. 29,5±4,8; p=0,04) no 4º mês; correlação negativa entre os escores do conhecimento e autocuidado no 2º mês (r=-0,48; p=0,03). Conclusão: O monitoramento convencional combinado ao monitoramento telefônico mostra-se eficaz no 4º mês com a melhoria do conhecimento e autocuidado de pacientes com insuficiência cardíaca e correlação significativa desses desfechos no 2º mês.

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