Rôle du microenvironnement apoptotique tissulaire et du MFG-E8 dans la modulation de la réponse inflammatoire

L’inflammation fait partie des processus réactionnels de défense dont dispose l’organisme en réponse aux agressions, assurant l’intégrité de l’hôte. En réponse au dommage tissulaire, plusieurs médiateurs inflammatoires interviennent dans le processus de l’inflammation. Lors de ces dommages, des signaux de dangers provenant de cellules endommagées sont relâchés dans l’environnement tissulaire, pouvant causer des dommages cellulaires et tissulaires. Les macrophages, tout comme d’autres cellules, peuvent être activés par ces signaux de danger, menant à la sécrétion de molécules telles que des cytokines et des chimiokines pouvant modifier le microenvironnement tissulaire. Les insultes au tissu sain peuvent entrainer la mort cellulaire telle que l’apoptose. Les molécules pouvant être relâchées lors de celle-ci contribuent au microenvironnement, notamment de par l’influence de celles-ci sur le macrophage. Parmi ces médiateurs, nous avons identifié le Milk Fat Globule-Epidermal growth factor 8 (MFG-E8), un acteur important dans la résolution de l’inflammation, comme étant relâché spécifiquement par les cellules apoptotiques. Nous avons émis l’hypothèse que le microenvironnement apoptotique tissulaire, via la relâche de MFG-E8, module le phénotype du macrophage, modifiant le microenvironnement, la réponse inflammatoire ainsi que le devenir de l’insulte tissulaire. Nos objectifs sont 1) de caractériser ce microenvironnement apoptotique tissulaire et la cinétique de relâche du MFG-E8 par les cellules apoptotiques, 2) d’en évaluer son rôle dans la modulation du phénotype du macrophage ainsi que 3) d’en étudier, in vivo, son influence sur l’environnement inflammatoire et le devenir tissulaire. Dans le premier article présenté, nous avons démontré que les cellules endothéliales apoptotiques relâchent le MFG-E8 de façon Caspase-3 dépendante. La stimulation des macrophages par l’environnement conditionné par les cellules endothéliales apoptotiques mène à l’adoption d’un profil macrophagien davantage anti-inflammatoire et moindrement pro-inflammatoire. Ce phénotype est réduit par l’inhibition de la Caspase-3 et il dépend de la présence de MFG-E8. De plus, le potentiel du MFG-E8 à la reprogrammation du macrophage pro-inflammatoire a été démontré via un modèle expérimental de péritonite. Ce changement phénotypique médié par MFG-E8 implique une signalisation STAT3. Ayant démontré que les cellules épithéliales apoptotiques, à l’instar des cellules endothéliales apoptotiques, relâchent elles aussi de façon apoptose-dépendante le MFG-E8, nous avons étudié plus exhaustivement un modèle in vivo riche en apoptose épithéliale, l’obstruction urétérale unilatérale. Dans ce deuxième article présenté, nous rapportons l’implication bénéfique de MFG-E8 dans ce modèle de pathologie rénale obstructive. Nous avons constaté que la présence ou l’administration de MFG-E8 réduit le dommage tissulaire et la fibrose. La protection conférée par MFG-E8 est médiée via la modulation de l’activation de l’inflammasome. De plus, nos résultats illustrent l’importance du phénotype anti-inflammatoire du macrophage médié par le MFG-E8 dans la régulation négative de l’activation de l’inflammasome rénal et du dommage tissulaire. Cette thèse présente la première description de la relâche Caspase-3-dépendante de MFG-E8 par les cellules apoptotiques. Elle démontre également l’importance du MFG-E8 dans le microenvironnement apoptotique inflammatoire dans l’atténuation du phénotype pro-inflammatoire du macrophage. De plus, nous avons démontré son rôle protecteur dans des modèles in vivo de transplantation aortique et de réparation tissulaire, de même que dans un modèle de maladie rénale chronique où nous avons montré que cette protection conférée par MFG-E8 est médiée par la régulation négative de l’inflammasome tissulaire. Nos résultats suggèrent ainsi que le MFG-E8 pourrait être considéré comme un interrupteur inflammatoire et ainsi comme une cible potentielle dans la modulation de maladies inflammatoires.

Modélisation de l’activité électrique des oreillettes avant et après ablation par cathéter

- Réalisé au centre de recherche de l'hospital du Sacré-Coeur de Montréal. - Programme conjoint entre Université de Montréal et École Polytechnique de Montréal.

Changes in Biochemical Composition in Indian Major Carps in Relation to size

Total biochemical composition of freshwater major carps, Labeo rohita -(r9hu); Catla catla (catla); Cirrltinus tnrigala (mrigal), in relation to size was evaluated . The water soluble nitrogen fraction constituted about 21% of the tota l nitro gen . Salt so luble fraction constituted 55 - 60% of the total nitrogen. Non-protein nitrogen represented 12% of the total nit rogen in all the cases except mri gal of small size (9.36%). The insoluble connec tive tissu e contributed to 2-3 per cent of tota l nitrogen . The monounsaturated fatty acid s (MUFA) formed 31-39% of the total fatty acids and 60-68% of the MUFA in freshwat er carps was CI 8:1. The esse ntial amino acids contributed to 41 to 51% of the total amino acid s in freshwater major carps. Arom atic amino acid content was sligh tly higher compared to marine fishe s while the proportion of proline was less. Varia tions in compos ition in rela tion to size are discu ssed . The autolytic activi ty was significantly higher in small fish in all the three species

Lesiones laríngeas post-intubación en adultos y su relación con el tiempo de intubación: Estudio de nasofibrolaringoscopia diagnóstica

Objetivo: Determinar las lesiones laríngeas post-intubación endotraqueal en la unidad de cuidado intensivo (UCI) y cirugía ambulatoria y evaluar su asociación con respecto al tiempo de intubación y otras variables clínico-demográficas en un hospital universitario. Materiales y métodos: Estudio de cohorte analítico incluyendo 60 pacientes (30 de UCI y 30 de cirugía ambulatoria) a quienes se les realizó nasofibrolaringoscopia a las 24 horas post-extubación y a las 3 semanas de control y se registran las lesiones laríngeas encontradas. Resultados: En la primera endoscopia el 70% de los pacientes de cirugía ambulatoria presentaban al menos una lesión laríngea con un promedio de duración de intubación de 0.12 días DS±0.05 desapareciendo todas las lesiones en la segunda endoscopia. En el análisis del grupo de UCI se encontraron lesiones en el 76.6% de los pacientes con un promedio de duración de intubación de 6.0 días DS±3.3. La presencia de edema en pacientes con intubación prolongada por más de 6 días mostró diferencias estadísticamente significativa con respecto al grupo con menos días de intubación (RR 3.048, 95% IC 0.9-9.3, P=0.03) al igual que con antecedente de EPOC (P=0.032) y APACHE II mayor de 17 (RR 1.8, 95% IC 1.114-3.0, P=0.013). EPOC tiene una diferencia estadísticamente significativa con hiperemia (P=0.02) y granuloma (P=0.019). En la segunda endoscopia se encontró mayor frecuencia de hiperemia en los pacientes con intubación prolongada (>6 días) con una diferencia estadísticamente significativa (P=0.01). Conclusión: La intubación prolongada se encuentra asociada a la aparición edema e hiperemia en la laringe. EPOC y puntaje superior de APACHE II se relacionan con hiperemia y granulomas glóticos.

Evaluation of the Larval Therapy in the Healing Process of Infected Wounds with Pseudomonas Aeruginosa in Rabbits

Introduction. During the last two decades the larval therapy has reemerged as a safe and reliable alternative for the healing of cutaneous ulcers that do not respond to the conventional treatments. Objective. To evaluate the use of the larvae of Lucilia sericata as a treatment for infected wounds with Pseudomonas aeruginosa in an animal model. Materials and methods. Twelve rabbits were randomly distributed in 3 groups: the first group was treated with larval therapy; the second was treated with antibiotics therapy and to the third no treatment was applied, therefore was established as a control group. To each animal a wound was artificially induced, and then a suspension of P. aeruginosa was inoculated into the lesion. Finally, every rabbit was evaluated until the infection development was recognized and treatment was set up for the first two groups according with the protocols mentioned above. Macroscopic evaluation of the wounds was based on the presence of edema, exudates, bad odor, inflammation around the wound and the presence of granulation tissue. The healing process was evaluated by monitoring histological changes in the dermal tissue. Results. Differences in the time required for wound healing were observed between the first group treated with larval therapy (10 days) and the second group treated with conventional antibiotics therapy (20 days). Conclusion. The L. sericata larva is and efficient tool as a therapy for infected wounds with P. aeruginosa.

Biological nutrient removal in SBR technology: from floccular to granular sludge

Biological nutrient removal has been studied and applied for decades in order to remove nitrogen and phosphorus from wastewater. However, more anthropogenic uses and the continued demand for water have forced the facilities to operate at their maximum capacity. Therefore, the goal of this thesis is to obtain more compact systems for nutrient removal from domestic wastewater. In this sense, optimization and long-term stabilization of high volume exchange ratios reactors, treating higher volumes of wastewater, have been investigated. With the same target, aerobic granular sludge was proposed as a reliable alternative to reduce space and increase loading rates in treatment plants. However, the low organic loading rate from low-strength influents (less than 1 Kg COD•m-3d-1) results in slower granular formation and a longer time to reach a steady state. Because of that, different methodologies and operational conditions were investigated in order to enhance granulation and nutrient removal from domestic wastewater.

Enteric coated spheres produced by extrusion/spheronization provide effective gastric protection and efficient release of live therapeutic bacteria

We present a novel but simple enteric coated sphere formulation containing probiotic bacteria (Lactobacillus casei). Oral delivery of live bacterial cells (LBC) requires live cells to survive firstly manufacturing processes and secondly GI microbicidal defenses including gastric acid. We incorporated live L. casei directly in the granulation liquid, followed by granulation, extrusion, spheronization, drying and spray coating to produce dried live probiotic spheres. A blend of MCC, calcium-crosslinked alginate, and lactose was developed that gave improved live cell survival during manufacturing, and gave excellent protection from gastric acid plus rapid release in intestinal conditions. No significant loss of viability was observed in all steps except drying, which resulted in approximately 1 log loss of viable cells. Eudragit coating was used to protect dried live cells from acid, and microcrystalline cellulose (MCC) was combined with sodium alginate to achieve efficient sphere disintegration leading to rapid and complete bacterial cell release in intestinal conditions. Viability and release of L. casei was evaluated in vitro in simulated GI conditions. Uncoated spheres gave partial acid protection, but enteric coated spheres effectively protected dried probiotic LBC from acid for 2 h, and subsequently released all viable cells within 1h of transfer into simulated intestinal fluid.

Selection of operational parameters for the production of instant soy protein isolate by pulsed fluid bed agglomeration

The objective of this study was to select the optimal operational conditions for the production of instant soy protein isolate (SPI) by pulsed fluid bed agglomeration. The spray-dried SPI was characterized as being a cohesive powder, presenting cracks and channeling formation during its fluidization (Geldart type A). The process was carried out in a pulsed fluid bed, and aqueous maltodextrin solution was used as liquid binder. Air pulsation, at a frequency of 600 rpm, was used to fluidize the cohesive SPI particles and to allow agglomeration to occur. Seventeen tests were performed according to a central composite design. Independent variables were (i) feed flow rate (0.5-3.5 g/min), (ii) atomizing air pressure (0.5-1.5 bar) and (iii) binder concentration (10-50%). Mean particle diameter, process yield and product moisture were analyzed as responses. Surface response analysis led to the selection of optimal operational parameters, following which larger granules with low moisture content and high process yield were produced. Product transformations were also evaluated by the analysis of size distribution, flowability, cohesiveness and wettability. When compared to raw material, agglomerated particles were more porous and had a more irregular shape, presenting a wetting time decrease, free-flow improvement and cohesiveness reduction. (C) 2010 Elsevier B.V. All rights reserved.

Route to turbulence in a trapped Bose-Einstein condensate

We have studied a Bose-Einstein condensate of (87)Rb atoms under an oscillatory excitation. For a fixed frequency of excitation, we have explored how the values of amplitude and time of excitation must be combined in order to produce quantum turbulence in the condensate. Depending on the combination of these parameters different behaviors are observed in the sample. For the lowest values of time and amplitude of excitation, we observe a bending of the main axis of the cloud. Increasing the amplitude of excitation we observe an increasing number of vortices. The vortex state can evolve into the turbulent regime if the parameters of excitation are driven up to a certain set of combinations. If the value of the parameters of these combinations is exceeded, all vorticity disappears and the condensate enters into a different regime which we have identified as the granular phase. Our results are summarized in a diagram of amplitude versus time of excitation in which the different structures can be identified. We also present numerical simulations of the Gross-Pitaevskii equation which support our observations. (C) 2011 by Astro Ltd. Published exclusively by WILEY-VCH Verlag GmbH & Co. KGaA

Identifying multi-view patterns with hierarchy and granularity based multimodal (HGM) cognitive model

Humans perceive entities such as objects, patterns, events, etc. as concepts, which are the basic units in human intelligence and communications. In addition, perceptions of these entities could be abstracted and generalised at multiple levels of granularity. In particular, such granulation allows the formation and usage of concepts in human intelligence. Such natural granularity in human intelligence could inspire and motivate the design and development of pattern identification approach in Data Mining. In our opinion, a pattern could be perceived at multiple levels of granularity and thus we advocate for the co-existence of hierarchy and granularity. In addition, granular patterns exist across different sources of data (multimodality). In this paper, we present a cognitive model that incorporates the characteristics of Hierarchy, Granularity and Multimodality for multi-view patterns identification in crime domain. Such framework is implemented with Growing Self Organising Maps (GSOM) and some experimental results are presented and discussed.

Work

WORK functions as both performance and document. It demonstrates some of what training-practice within a hybrid arts practice might be and performatively places into action an investigation into solo work and multi art form collaboration.

WORK

Steph Hutchison's solo WORK is fuelled by an interest in pushing the body to its physical limit. A hybrid performance, interweaving dance, circus arts, improvisation, sports and theatre, WORK is inspired by the physical journey of Julie Moss. In 1982, Julie Moss competed in her first Ironman without ever completing the total distance before. What began as a lark became a struggle for survival and a test of human will. Each time she felt like quitting, she thought it was her 'ego trying to self-sabotage,' but her real self was 'that voice that said; "just keep moving forward. There is no limit." Hutchison explores the notion of dance as extreme sport and emphatically engages her body in rigorous physical practices. Her attention is to muscularity and the performance of effort, work and labour, to the point of physical exhaustion. Using circus apparatus such as tissu, rope and acrobatic mats, Steph pushes to and beyond the limits of her physical ability during the performance. In preparation for the show, she puts herself through intense bootcamp style training, classical and contemporary dance training and teaches herself new acrobatic tricks. Her aim is to push herself past exhaustion to another level.

Development and characterization of the 2,4,6-trichlorophenol (2,4,6-TCP) aerobic degrading granules in sequencing batch airlift reactor

2,4,6-trichlorophenol (2,4,6-TCP) aerobic degrading granules were successfully developed in the sequencing batch airlift reactor. The key strategy used in cultivation of the granules was dosing glucose and acetate as co-substrates. After granulation, average concentrations of 2,4,6-TCP and COD in the effluent were less than 8mgL-1 and 59mgL-1, respectively. The removal efficiencies of 2,4,6-TCP and COD were above 93% and 90%, respectively. The specific degradation rate of 2,4,6-TCP peaked at 61mg 2,4,6-TCP gVSS-1h-1 when inoculated at the concentration of 400mgL-1. The extracellular polymeric substance (EPS) contents of the 2,4,6-TCP aerobic degrading granules were decreased compared with the contents in seed sludge. Two peaks attributed to the protein-like fluorophores were identified by three-dimensional excitation emission matrix (EEM) fluorescence spectra. The decrease of fluorescence parameters, e.g., peak locations, intensities, indicated quenching effect of 2,4,6-TCP on the EPS fluorescence. Meanwhile, the shift of peak position indicated chemical changes of the EPS.

Estudo da viabilidade técnica da utilização de escórias de aciaria do processo LD como adição em cimentos

A reciclagem de resíduos apresenta-se como uma alternativa adequada com relação à preservação dos recursos naturais e do meio ambiente. As escórias de aciaria são resíduos siderúrgicos originados na fabricação do aço, e são geradas em grandes quantidades. Estes resíduos são estocados nos pátios siderúrgicos, onde permanecem, na sua maioria, sem qualquer destino. Normalmente, as escórias de aciaria são volumetricamente instáveis, apresentando características expansivas, e por esta razão, a aplicação das mesmas em materiais de construção torna-se restrita. Esta pesquisa tem como objetivo estudar a viabilidade técnica do uso das escórias de aciaria LD como adição em cimentos, propondo um método de estabilização por meio de granulação por resfriamento brusco destas escórias, buscando, desta forma, a eliminação do fenômeno da expansão, e visando a melhoria das características destes resíduos. No processo de estabilização, a escória líquida foi granulada em uma usina siderúrgica. Estudos complementares de granulação foram realizados nos laboratórios da UFRGS, empregando-se escórias refundidas. A granulação por resfriamento brusco favoreceu a redução do CaOlivre, a eliminação do MgO na forma de periclásio, e a eliminação do bC2S das escórias, considerados agentes causadores da expansão. No entanto, a elevada basicidade da escória LD dificulta a formação da estrutura vítrea e a separação da fração metálica após o resfriamento brusco. Foram realizados ensaios de expansão das escórias, atividade pozolânica, e resistência mecânica de argamassas com escórias granuladas. O resfriamento brusco proporcionou a eliminação da expansão e o desenvolvimento das propriedades pozolânicas/cimentícias da escória granulada. Como adição em cimentos, do ponto de vista da resistência mecânica, as argamassas compostas com escórias granuladas e clínquer apresentaram níveis de resistência à compressão axial compatíveis com as especificações referentes ao cimento Portland composto, apesar destes resultados serem inferiores aos obtidos para as argamassas de referência.

Colesteatomas adquiridos : análise comparativa da perimatriz entre pacientes pediátricos e adultos

Introdução: Os colesteatomas podem ocorrer tanto em crianças como em adultos, porém nas crianças pareceriam ter um crescimento mais agressivo e extenso. A atividade das colagenases poderia explicar este perfil. Objetivo: Comparar, histologicamente, a perimatriz de colesteatomas adquiridos de crianças com os de adultos. Métodos: Foram estudados 74 colesteatomas, 35 pediátricos, coletados em cirurgias otológicas, fixados em formol 10% e processados pelas técnicas histológicas habituais. Foram preparadas uma lâmina em Hematoxilina-Eosina (HE) e outra em Picrossírios, de cada amostra, e analisadas ao microscópio óptico. A leitura foi “cega”, efetuada por meio de imagens digitais, no software ImagePro Plus. A análise estatística foi realizada através dos coeficientes de correlação de Pearson e Spearman e dos testes t e χ2, sendo considerados como estatisticamente significativos os valores de P<0,05. Resultados: Dos 74 colesteatomas coletados, 17 - sete do grupo pediátrico e dez do adulto - foram excluídos por não terem presença de matriz e perimatriz nas lâminas processadas. A média±dp da idade, no grupo pediátrico, foi de 12,85±3,63; e no adulto, 33,69±13,10. Na análise histológica, o número médio de camadas de células epiteliais da matriz foi igual a oito, nos dois grupos, 60% das amostras apresentavam inflamação, de moderada a acentuada; quanto à fibrose, nas crianças, 71,4% e nos adultos, 62,1%; o granuloma apareceu em 10,7% e 13,8%, respectivamente; a presença de epitélio cubóide simples delimitando a perimatriz foi encontrada em 29% dos infantis e 14% dos adultos, entretanto, nenhuma dessas variáveis apresentou diferença estatisticamente significativas quando comparadas por faixa etária (P>0,05). Quanto à espessura da perimatriz, no grupo pediátrico, as medianas (intervalo interquartil) dos parâmetros foram: média=79 (41 a 259); mediana=77 (40 a 265); soma=1.588 (831 a 5.185); delta=82 (44 a 248); mínimo=53 (16 a 165) e máximo=127 (64 a 398); já no grupo de adultos foram: média=83 (26 a 174); mediana=68 (30 a 181); soma=1.801 (558 a 3.867); delta=92 (45 a 190); mínimo=27 (12 a 100) e máximo=136 (53 a 280). O coeficiente de Spearman mostrou correlação inversa, moderada, entre a espessura da perimatriz e a idade; também houve correlação, forte, entre a espessura da perimatriz e o número de camadas da matriz, porém não houve correlação entre essa com a idade. Conclusão: Histologicamente, a perimatriz de colesteatomas adquiridos, de crianças e adultos, vista à microscopia óptica, apresenta-se como um tecido conjuntivo denso de espessura variável (intra e interpacientes), que, por vezes, exibe infiltrado inflamatório linfoplasmocitário e/ou tecido de granulação e reação de corpo estranho; em alguns casos é delimitada em plano profundo por epitélio cubóide simples. Há correlação inversa, de fraca a moderada, entre o tamanho da perimatriz, medida em micrômetros e a idade do paciente na data da cirurgia. O grau de inflamação da perimatriz apresenta correlação, de moderada a forte, com a espessura da perimatriz. As espessuras da matriz e da perimatriz estão fortemente correlacionadas.