Role of extracellular microvesicles in celiac disease as potential pathogenetic agents and biomarkers of intestinal inflammation

BACKGROUND AND AIM: Celiac Disease (CD) is a chronic intestinal disease caused by the ingestion of gluten. Microvesicles (MVs) belong to a heterogeneous population, released by cells both in homeostasis and pathological conditions. MVs can be considered mediators of inflammation and potential biomarkers. The aim of this study is: 1) to evaluate the possible role of MVs in the propagation of inflammation in CD, using MVs purified by supernatant of duodenal biopsies from CD patients; 2) to identify potential biomarkers by proteomic analysis of pasma-derived MVs from CD patients. MATERIAL AND METHODS: MVs were isolated by molecular exclusion chromatography and ultracentrifugation respectively from plasma and culture supernatant of duodenal biopsies of 10 active CD, 5 remission CD and 6 controls. Proteomic analysis of plasma-derived MVs was performed by mass spectrometry. The possible effects of duodenal-derived MVs on confluent Caco-2 cells were evaluated by measuring Transepithelial Electrical Resistance (TEER) and analyzing the expression of actin, tissue transglutaminase (TG2) and Zonula Occludens-1 (ZO-1). The dosage of IL-8 in the Caco-2 culture supernatant was carried out by ELISA test. The statistical analysis of the data obtained was performed using the Student's t-test. RESULTS: The proteomic analysis of circulating MVs showed 8 proteins from desmosome and cytoskeleton (desmoglein-1 and gamma-enteric actin) associated with the active phase of the disease. Caco-2 cells, treated with the MVs purified from the duodenal biopsies of active CD patients showed: 1) rearrangement of actin filaments; 2) increased expression of TG2; 3) decreased expression of the ZO-1 protein, although an alteration of intestinal permeability was not observed. The analysis of Caco-2 cell supernatants showed a statistically significant increase in IL-8 (p <0.05), in the presence of MVs isolated from biopsies of active CD patients, compared to remission CD patients and controls. CONCLUSIONS: MVs isolated from plasma of active CD patients could represent potential diagnostic and prognostic biomarkers. Although they don’t induce changes in intestinal permeability, MVs could contribute to inflammatory cascade increasing IL-8 production

Dimorfismo sexual e as variações sazonais na troca de gases foliares da erva-mate cultivada em dois ambientes luminosos.

Erva-mate (Ilex paraguariensis St. Hil., Aquifoliaceae) é uma árvore subtropical, sempre verde e dióica

Modelagem da estrutura e da arquitetura de erva-mate.

RESUMO: A arquitetura vegetal permite representar mais realisticamente as interações da planta com seu ambiente, minimizando a ocorrência de fracassos nos estudos que assumem um comportamento biológico baseado em estimativas médias. A modelagem de arquitetura vegetal é uma área de pesquisa nova e promissora na América do Sul. Este trabalho tem como objetivos apresentar os conceitos básicos envolvidos na modelagem da estrutura e da arquitetura de plantas, e relatar as pesquisas em desenvolvimento sobre a análise da estrutura de crescimento da erva-mate (Ilex paraguariensis St. Hil.). No ciclo anual da erva-mate apresentam-se regularmente duas pausas no crescimento que separam as brotações anuais em duas unidades de crescimento (GU) sucessivas. No experimento em campo com 30 plantas adultas foram medidos os parâmetros morfológicos durante dois anos (período entre duas podas). O desenvolvimento arquitetural das plantas está sendo analisado em várias escalas, com o uso do sistema computacional francês denominado AMAPmod. Características não medidas nas plantas adultas, como o padrão de ramificações, foram obtidas em um experimento realizado com plantas jovens. Atualmente estão sendo construídos histogramas e seqüências dos metâmeros das GU?s presentes nos eixos principais das plantas adultas, visando determinar o padrão de crescimento caulinar da erva-mate. Espera-se que a codificação dos ramos das plantas jovens contribua para a obtenção do modelo de desenvolvimento topológico. Esse modelo permitirá observar as caracterizações locais (posição de entrenós) e globais (comprimento de ramos) da espécie. A reconstrução de plantas em 3D considera as inclinações e o azimute de ramos e de componentes foliares recuperados a partir de fotografias, incluindo a diferenciação sexual das plantas.SBIAgro 2007. Na publicação: Silvio Roberto de Medeiros Evangelista

Propriedades ecofisiológicas, químicas e sensoriais da erva-mate.

A erva-mate (Ilex paraguariensis, St. Hil.), originária da América do Sul, é importante no preparo de bebidas tonificantes e estimulantes, devido à presença de metil-xantinas (cafeína, teobromina e teofilina)

Fotossíntese líquida foliar da erva-mate em escala diária.

O objetivo deste trabalho foi determinar a curva de curso diário da fotossíntese líquida (A) da erva-mate (Ilex paraguaniensis St. Hil., Aquifoliaceae

Distribuição e número de estômatos em folhas da erva-mate cultivada em dois ambientes com luminosidade distinta.

Objetivou-se determinar as diferenças no número e na distribuição de estômatos na epiderme de folhas de idades distintas, originadas em plantas cultivadas em monocultura (MO) e na floresta primária antropizada (FUS)

SAT0305 Histology of minor salivary glands in patients with sjÖgren's syndrome, association with clinical and laboratory aspects

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Delayed diagnosis of coeliac disease increases cancer risk

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Participatory instructional redesign by students and teachers in secondary education: effects on perceptions of instruction

Könings, K. D., Brand-Gruwel, S., & Van Merriënboer, J. J. G. (2011). Participatory instructional redesign by students and teachers in secondary education: effects on perceptions of instruction. Instructional Science, 39(5), 737–762.Students’ perceptions of instruction are important because they direct the learning of students. The fact that teachers have only limited knowledge of these perceptions is likely to threaten the effectiveness of learning, because congruence between interpretations of an instructional intervention is necesarry for its optimal use. This study examines participatory design as a strategy for taking student perceptions into account in instructional re/design. Participatory design meetings of groups of teachers and seven co-designing students in a secondary education setting identified changes to improve the regular education process. The results on changes in student perceptions, perceived-desired discrepancy, and teacher-student disagreement showed some improvement for the co-designers but, unexpectedly, limited or even negative effects for the non-co-designing students. Possible causes are discussed. Participatory design seems to have potential for improving education, but further research is needed

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes