M2 Macrophages Activate WNT Signaling Pathway in Epithelial Cells: Relevance in Ulcerative Colitis

Macrophages, which exhibit great plasticity, are important components of the inflamed tissue and constitute an essential element of regenerative responses. Epithelial Wnt signalling is involved in mechanisms of proliferation and differentiation and expression of Wnt ligands by macrophages has been reported. We aim to determine whether the macrophage phenotype determines the expression of Wnt ligands, the influence of the macrophage phenotype in epithelial activation of Wnt signalling and the relevance of this pathway in ulcerative colitis. Human monocyte-derived macrophages and U937-derived macrophages were polarized towards M1 or M2 phenotypes and the expression of Wnt1 and Wnt3a was analyzed by qPCR. The effects of macrophages and the role of Wnt1 were analyzed on the expression of β-catenin, Tcf-4, c-Myc and markers of cell differentiation in a co-culture system with Caco-2 cells. Immunohistochemical staining of CD68, CD206, CD86, Wnt1, β-catenin and c-Myc were evaluated in the damaged and non-damaged mucosa of patients with UC. We also determined the mRNA expression of Lgr5 and c-Myc by qPCR and protein levels of β-catenin by western blot. Results show that M2, and no M1, activated the Wnt signaling pathway in co-culture epithelial cells through Wnt1 which impaired enterocyte differentiation. A significant increase in the number of CD206+ macrophages was observed in the damaged mucosa of chronic vs newly diagnosed patients. CD206 immunostaining co-localized with Wnt1 in the mucosa and these cells were associated with activation of canonical Wnt signalling pathway in epithelial cells and diminution of alkaline phosphatase activity. Our results show that M2 macrophages, and not M1, activate Wnt signalling pathways and decrease enterocyte differentiation in co-cultured epithelial cells. In the mucosa of UC patients, M2 macrophages increase with chronicity and are associated with activation of epithelial Wnt signalling and diminution in enterocyte differentiation

A História da Alimentação: balizas historiográficas

Os M. pretenderam traçar um quadro da História da Alimentação, não como um novo ramo epistemológico da disciplina, mas como um campo em desenvolvimento de práticas e atividades especializadas, incluindo pesquisa, formação, publicações, associações, encontros acadêmicos, etc. Um breve relato das condições em que tal campo se assentou faz-se preceder de um panorama dos estudos de alimentação e temas correia tos, em geral, segundo cinco abardagens Ia biológica, a econômica, a social, a cultural e a filosófica!, assim como da identificação das contribuições mais relevantes da Antropologia, Arqueologia, Sociologia e Geografia. A fim de comentar a multiforme e volumosa bibliografia histórica, foi ela organizada segundo critérios morfológicos. A seguir, alguns tópicos importantes mereceram tratamento à parte: a fome, o alimento e o domínio religioso, as descobertas européias e a difusão mundial de alimentos, gosto e gastronomia. O artigo se encerra com um rápido balanço crítico da historiografia brasileira sobre o tema

Prospectively recorded versus medical record-derived spinal cord Injury scores in dogs with intervertebral disk herniation

BACKGROUND : Validated spinal cord injury (SCI) scores have been established for veterinary species but are not uniformly used in practice. HYPOTHESIS/OBJECTIVES : To determine the level of agreement of SCI scores at the time of admission versus those assigned from reconstructed medical records in a population of dogs with intervertebral disk herniation (IVDH). ANIMALS : Eighty-six client-owned dogs with confirmed IVDH. METHODS : Retrospective study. Medical records were reviewed for history, physical examination, neurologic examination, and recorded Modified Frankel score (MFS) and Texas spinal cord injury score (TSCIS) at the time of admission. Three raters, all board-certified neurologists, assigned MFS and TSCIS based on digitized abstracted medical records to each patient. These scores were then compared to the recorded score at the time of admission. RESULTS : Actual agreement for MFS and TSCIS derived from medical records by the 3 raters compared to prospectively derived MFS and TSCIS was 77.9 and 51.2%, respectively. A kappa value of 0.572 (95% CI 0.450, 0.694; P < .001) and an ICC of 0.533 (95% CI 0.410, 0.646; P < .001) were calculated for MFS scores. A kappa value of 0.100 (95% CI 0.000, 0.222; P = .107), and an ICC of 0.503 (95% CI 0.377, 0.620; P < .001) were calculated for TSCIS scores. CONCLUSIONS AND CLINICAL IMPORTANCE : Results showed that SCI scores recorded at the time of admission often do not agree with those retrospectively abstracted from medical records. Agreement was less when using the more complex TSCIS scale and therefore the MFS scale might be more appropriate for use in retrospective studieshttp://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1939-1676hb2013ab201