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Santos, Fernanda Faquim. "Avaliação de Imunomarcação de COX-2 em Carcinomas Intestinais Caninos." Universidade Estadual Paulista (UNESP), 2018. http://hdl.handle.net/11449/154162.
Анотація:
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Devido ao aumento da expectativa de vida dos animais de estimação, o aparecimento de neoplasias tem se tornado uma importante afecção na Medicina Veterinária. As neoplasias gastrointestinais de cães são pouco diagnosticadas e sua etiologia é desconhecida. As localizações mais frequentes são o jejuno, cólon e reto. Objetivou-se avaliar a Cox-2 por meio de imunohistoquímica e a intensidade de PAS positivo nas amostras de intestinos de cães saudáveis (GS) e com neoplasia (GN). As neoplasias foram classificadas por análise histopatológica. As diferenças foram significativas quando P<0.05 (testes não paramétricos). Nas amostras neoplásicas observou-se imunodetecção acentuada de COX-2, quando comparadas aos cães saudáveis, com diferenças significativas entre os grupos. O mesmo ocorreu para a intensidade de PAS, onde se observou diminuição do número de células caliciformes e aumento na produção de muco nas amostras neoplásicas, enquanto nas amostras saudáveis observou-se marcação intensa nas células caliciformes. Com isso pode-se concluir que a COX está envolvida na capacidade do tumor evadir as defesas do sistema imunológico. Apesar da relação entre o processo inflamatório, mais especificamente o papel das prostaglandinas, e o desenvolvimento e propagação tumoral ser bastante claro, ainda muito se têm a ser esclarecido.
Due to the increase in the life expectancy of the pets, the appearance of neoplasias has become an important affection in the Veterinary Medicine. Gastrointestinal neoplasms of dogs are poorly diagnosed and their etiology is unknown. The most frequent locations are jejunum, colon and rectum. The objective of this study was to evaluate Cox-2 by means of immunohistochemistry and the positive PAS intensity in intestinal samples from healthy dogs (GS) and neoplasia (GN). The neoplasms were classified by histopathological analysis. The differences were significant when P <0.05 (non-parametric tests). In the neoplastic samples, marked COX-2 immunodetection was observed when compared to healthy dogs, with significant differences between groups. The same was observed for PAS intensity, where a decrease in the number of goblet cells and an increase in the mucus production were observed in the neoplastic samples, while in the healthy samples intense marking was observed in the goblet cells. With this we can conclude that COX is involved in the ability of the tumor to evade the defenses of the immune system. Although the relationship between the inflammatory process, more specifically the role of prostaglandins, and tumor development and propagation is very clear, much remains to be elucidated.
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Lima, Glaucia Carielo. "Efeito dos oligossacarídeos FOS e GOS na microbiota intestinal e no pH do conteúdo cecal de ratas Wistar em desenvolvimento." [s.n.], 2010. http://repositorio.unicamp.br/jspui/handle/REPOSIP/255060.
Анотація:
Orientador: Mário Roberto Maróstica JuniorDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia de Alimentos
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Resumo: Muitos estudos tem demonstrado que o consumo acumulado de galactooligossacarídeo (GOS) e frutooligossacarídeo (FOS) pode trazer benefícios significativos para a saúde, relacionados com a sua resistência à digestão, sendo utilizados como substrato pelas bactérias intestinais, em especial as bifidobactérias. O objetivo do presente trabalho foi avaliar os efeitos de alteração de pH e microbiota (contagem de Bifidobacterium e Lactobacillus) no intestino grosso de ratas Wistar após o consumo dos oligossacarídeos não digeríveis (ONDs) FOS e GOS. Foram confeccionadas quatro dietas baseadas na AIN93G para roedores utilizando os ONDs em substituição parcial à sacarose para os grupos experimentais. Desta forma, o experimento contou com quatro grupos experimentais, sendo: grupo Controle, grupo FOS, grupo GOS e grupo FOS + GOS. O ensaio biológico contou com 32 animais divididos em grupos de 8 animais cada, mantidos em gaiolas separadas, sob ciclo claro/escuro de 12 horas, com temperatura e umidade controladas, durante o período de 90 dias. O consumo de dieta e o ganho de peso foram monitorados. Ao final do experimento, os animais foram sacrificados por decapitação, seu ceco retirado para coleta de material para análises posteriores de pH e microbiota intestinal. A análise de pH foi realizada por meio de peagômetro digital (TEC 5MP, Tecnal) e a análise de microbiota, a partir de diluições do conteúdo fecal e inoculação em meios de cultura específicos. Todas as placas foram incubadas em câmaras de anaerobiose contendo sistema gerador de anaerobiose Anaerogen (Oxoid Ltd., Basingstoke, Hampshire, England) durante 24 - 48 horas a 37°C. Os resultados foram e xpressos na forma do logaritmo decimal das unidades formadoras de colônia/g material (Log10 UFC). Para a análise estatística, foi utilizado o software GraphPad Prism 5.0. A análise de variância (ANOVA) foi realizada e os dados paramétricos foram analisados por meio do teste de Tukey, a 5% de significância e os não paramétricos por teste de Dunnett. Os resultados obtidos demonstraram um abaixamento do pH intestinal nos grupos que consumiram FOS e FOS + GOS e aumento da contagem de Bifidobacterium no conteúdo cecal dos grupos FOS, GOS e FOS + GOS e aumento de Lactobacillus dos grupos FOS e FOS + GOS
Abstract: Many studies have shown that consumption of galactooligosaccharide (GOS) and fructooligosaccharides (FOS) can bring significant benefits to health. NDC are used as substrate by intestinal bacteria, especially bifidobacteria, as these compounds are resistance to digestion. The aim of this study was to evaluate the effects in pH and microbiota (specifically for Lactobacillus and Bifidobacterium growth) in the large intestine of Wistar rats after consumption of non-digestible oligosaccharides (NDOs) FOS and GOS. Four different diets were produced, based on the AIN93G formula for rodents, using NDOs in partial replacement of sucrose by prebiotics FOS and GOS for the experimental groups. Thus, the experiment had four experimental groups, as described: Control group, FOS group, GOS group and FOS + GOS group. For the 'in vivo¿ experiment, the 32 animals were divided into groups of 8 animals each. The rats were kept in separate cages under light / dark cycles of 12 hours, with controlled temperature and humidity during 90 days. The diet consumption and weight gain were monitored. At the end of the experiment, the animals were killed by decapitation, their cecum removed to collect material for further analysis of pH and intestinal microbiota. The pH analysis was performed using digital pH meter (TEC 5MP Tecnal) and analysis of microbiota from dilutions of fecal contents and inoculation on specific culture media. All plates were incubated in anaerobic chambers containing anaerobic generation system Anaerogen (Oxoid Ltd., Basingstoke, Hampshire, England) for 24-48 hours at 37 °C. The results were expressed as the logarithm of colony forming units / g material (Log10 CFU). For statistical analysis, GraphPad Prism 5.0 was used. The analysis of variance (ANOVA) was performed and parametric data were analyzed using the Tukey test at 5% significance and the nonparametric by Dunnett's test. The results showed a lowering of intestinal pH in the groups consuming FOS and FOS + GOS and increased count of Bifidobacterium in the cecal contents of the groups FOS, GOS and FOS + GOS and increase of Lactobacillus in the groups FOS and FOS + GOS
Mestrado
Nutrição Experimental e Aplicada à Tecnologia de Alimentos
Mestre em Alimentos e Nutrição
3
Tamoutounour, Samira. "Origine et fonction des cellules dendritiques, des monocytes et des macrophages de la peau et de l'intestin." Thesis, Aix-Marseille, 2013. http://www.theses.fr/2013AIXM4023.
Анотація:
Les plus grandes interfaces avec l'environnement extérieur sont la peau, et les muqueuses gastro-intestinales. Ces barrières, sont constamment menacées par des attaques physico-chimiques ou par des tentatives d'invasion de micro-organismes. Les phagocytes mononucléés qui comprennent les DCs, les monocytes et les macrophages et sont issus de la lignée myéloïde possèdent des propriétés distinctes de phagocytose de pathogènes et de cellules apoptotiques, d'apprêtement des antigènes et de présentation de ces derniers aux lymphocytes T. d'activation. La distinction de ces différentes cellules est un enjeu majeur pour la compréhension des mécanismes de la réponse immune et pour sa modulation dans des buts thérapeutiques. En utilisant des marqueurs cellulaires Ly-6C, CD64 et ainsi que le fait que les monocytes dépendent du récepteur de chimiomokine CCR2 pour émigrer de la moelle osseuse et les DCs de l'engagement du récepteur Flt3, nous avons montré pour la première fois qu'il existe dans la peau et l'intestin une cascade de différenciation qui conduit à des monocytes et des macrophages tissulaires et est distincte de celle donnant naissance aux DCs. Nous avons ensuite étudié le comportement de ces cellules dans une inflammation stérile dans la peau médiée par le DNFB (dinitrofluorobenzène) et dans une maladie inflammatoire de l'intestin (IBD) et montré que leurs capacités de migration vers les ganglions lymphatiques et de présentation antigénique à des lymphocytes T sont dépendantes du modèle utilisé. Cette déconvolution des populations tissulaires de cellules monuclées nous permet ainsi de disséquer le rôle de chacun de ces acteurs lors de la réponse immuneThe skin and the gastrointestinal mucosa that are the largest interfaces with the external environment. These barriers are the guardians of the body's integrity and are constantly threatened by physicochemical or microorganisms attacks. They have a dense network of effector cells dedicated to the defense of the body. Among them, mononuclear phagocytes which include DCs, monocytes and macrophages are all derived from the myeloid lineage and possess distinct properties of pathogens and apoptotic cells phagocytosis, antigens processing and presentation to T cells. However, DCs, monocytes and macrophages share common ancestry and functions and are hard to differentiate from each other in tissues and lymphoid organs. The distinction of these cells is a major challenge for understanding immune response's mechanisms and its modulation for therapeutic purposes.Using Ly-6C, CD64 and CCR2 as cell markers, as well as the CCR2 dependent emigration from bone marrow of monocytes and DCs dependency to Flt3-L, we have shown for the first time a cascade of monocytes differentiation, and separate populations of tissue monocytes, macrophages and DCs within the skin and the intestine. We then studied the behavior of these cells in a sterile skin inflammation mediated by DNFB (dinitrofluorobenzène) and in an inflammatory bowel disease (IBD) and showed that their ability to migrate to lymph nodes and to present antigens to naïve T lymphocytes are model dependent. Disentangling those tissue populations allows us to dissect the role of each of these actors in the immune response
4
Ashwood, Paul. "Microparticles and the intestine." Thesis, King's College London (University of London), 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.272223.
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Fragkos, K. "Citrulline and the intestine." Thesis, University College London (University of London), 2018. http://discovery.ucl.ac.uk/10047511/.
Анотація:
Citrulline, a non-protein amino acid, has been playing an important role in scientific research over the last few years. This thesis explores various aspects of citrulline with respect to intestinal disease, short bowel syndrome and intestinal failure. The first important finding was that citrulline as a term has been used at the end of the 19th century-beginning of the 20th century to describe an extract of the C. colocynthis, used as a subcutaneous laxative. Also, old sources have revealed that citrulline was first described as an amino acid by Koga and Ohtake (1914) and not by Wada (1930a). From the systematic review and meta-analysis, citrulline levels are strongly positively correlated with small bowel length in short bowel syndrome patients and strongly negatively correlated with intestinal disease severity with regards to enteropathies (coeliac disease, tropical enteropathy, mucositis, acute rejection in intestinal transplantation, but not Crohn’s disease). Citrulline cut-off levels have an overall sensitivity and specificity of 80% and citrulline levels compared to controls were reduced by 10 μmol/L. These findings suggest that citrulline is a marker of possible acute intestinal injury or intestinal insufficiency. Next, an original five-by-five cross-over study was designed (Williams design) comparing post-absorptive amino acid concentrations after challenges with citrulline, arginine, glutamine, 3-methyl-hisitidine and placebo. Citrulline was the most potent stimulator for all other amino acids, contrary to beliefs of glutamine challenges. Citrulline challenges could be useful in intestinal failure but also in liver failure where urea cycle pathways including glutamine, arginine and ornithine are implicated. The final study was an investigation of quality of life in short bowel syndrome patients. The quality of life scale is highly reliable in short bowel syndrome patients (Cronbach’s alpha > 0.700) and the main causes of low quality of life are fatigue, diarrhoea/increased stomal output, lack of sleep, gastrointestinal symptoms, and muscle pains.
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Rothe, Monique. "Response of intestinal Escherichia coli to dietary factors in the mouse intestine." Phd thesis, Universität Potsdam, 2013. http://opus.kobv.de/ubp/volltexte/2013/6638/.
Анотація:
Diet is a major force influencing the intestinal microbiota. This is obvious from drastic changes in microbiota composition after a dietary alteration. Due to the complexity of the commensal microbiota and the high inter-individual variability, little is known about the bacterial response at the cellular level. The objective of this work was to identify mechanisms that enable gut bacteria to adapt to dietary factors. For this purpose, germ-free mice monoassociated with the commensal Escherichia coli K-12 strain MG1655 were fed three different diets over three weeks: a diet rich in starch, a diet rich in non-digestible lactose and a diet rich in casein. Two dimensional gel electrophoresis and electrospray tandem mass spectrometry were applied to identify differentially expressed proteins of E. coli recovered from small intestine and caecum of mice fed the lactose or casein diets in comparison with those of mice fed the starch diet. Selected differentially expressed bacterial proteins were characterised in vitro for their possible roles in bacterial adaptation to the various diets. Proteins belonging to the oxidative stress regulon oxyR such as alkyl hydroperoxide reductase subunit F (AhpF), DNA protection during starvation protein (Dps) and ferric uptake regulatory protein (Fur), which are required for E. coli’s oxidative stress response, were upregulated in E. coli of mice fed the lactose-rich diet. Reporter gene analysis revealed that not only oxidative stress but also carbohydrate-induced osmotic stress led to the OxyR-dependent expression of ahpCF and dps. Moreover, the growth of E. coli mutants lacking the ahpCF or oxyR genes was impaired in the presence of non-digestible sucrose. This indicates that some OxyR-dependent proteins are crucial for the adaptation of E. coli to osmotic stress conditions. In addition, the function of two so far poorly characterised E. coli proteins was analysed: 2 deoxy-D gluconate 3 dehydrogenase (KduD) was upregulated in intestinal E. coli of mice fed the lactose-rich diet and this enzyme and 5 keto 4 deoxyuronate isomerase (KduI) were downregulated on the casein-rich diet. Reporter gene analysis identified galacturonate and glucuronate as inducers of the kduD and kduI gene expression. Moreover, KduI was shown to facilitate the breakdown of these hexuronates, which are normally degraded by uronate isomerase (UxaC), altronate oxidoreductase (UxaB), altronate dehydratase (UxaA), mannonate oxidoreductase (UxuB) and mannonate dehydratase (UxuA), whose expression was repressed by osmotic stress. The growth of kduID-deficient E. coli on galacturonate or glucuronate was impaired in the presence of osmotic stress, suggesting KduI and KduD to compensate for the function of the regular hexuronate degrading enzymes under such conditions. This indicates a novel function of KduI and KduD in E. coli’s hexuronate metabolism. Promotion of the intracellular formation of hexuronates by lactose connects these in vitro observations with the induction of KduD on the lactose-rich diet. Taken together, this study demonstrates the crucial influence of osmotic stress on the gene expression of E. coli enzymes involved in stress response and metabolic processes. Therefore, the adaptation to diet-induced osmotic stress is a possible key factor for bacterial colonisation of the intestinal environment.Sowohl Humanstudien als auch Untersuchungen an Tiermodellen haben gezeigt, dass die Ernährung einen entscheidenden Einfluss auf die Zusammensetzung der Darmmikrobiota hat. Aufgrund der Komplexität der Mikrobiota und der inter individuellen Unterschiede sind die zellulären Mechanismen, die dieser Beobachtung zugrunde liegen, jedoch weitgehend unbekannt. Das Ziel dieser Arbeit war deshalb, Anpassungsmechanismen von kommensalen Darmbakterien auf unterschiedliche Ernährungsfaktoren mittels eines simplifizierten Modells zu untersuchen. Dazu wurden keimfreie Mäuse mit Escherichia coli MG1655 besiedelt und drei Wochen mit einer stärkehaltigen, einer laktosehaltigen oder einer kaseinhaltigen Diät gefüttert. Mittels zwei dimensionaler Gelelektrophorese und Elektrospray Ionenfallen-Massenspektrometrie wurde das Proteom der intestinalen E. coli analysiert und differentiell exprimierte bakterielle Proteine in Abhängigkeit der gefütterten Diät identifiziert. Die Funktion einiger ausgewählter Proteine bei der Anpassung von E. coli auf die jeweilige Diät wurde im Folgenden in vitro untersucht. E. coli Proteine wie z.B. die Alkylhydroperoxid Reduktase Untereinheit F (AhpF), das DNA Bindeprotein Dps und der eisenabhängige Regulator Fur, deren Expression unter der Kontrolle des Transkriptionsregulators OxyR steht, wurden stärker exprimiert, wenn die Mäuse mit der laktosehaltigen Diät gefüttert wurden. Reportergenanalysen zeigten, dass nicht nur oxidativer Stress, sondern auch durch Kohlenhydrate ausgelöster osmotischer Stress zu einer OxyR abhängigen Expression der Gene ahpCF and dps führte. Weiterhin wiesen E. coli Mutanten mit einer Deletion der ahpCF oder oxyR Gene ein vermindertes Wachstum in Gegenwart von nicht fermentierbarer Saccharose auf. Das spricht dafür, dass OxyR abhängige Proteine eine wichtige Rolle bei der Anpassung von E. coli an osmotischen Stress spielen. Weiterhin wurde die Funktion von zwei bisher wenig charakterisierten E. coli Proteinen untersucht: die 2 Deoxy D Glukonate 3 Dehydrogenase (KduD) wurde im Darm von Mäusen, die mit der laktosehaltigen Diät gefüttert wurden, induziert, während dieses Protein und die 5 Keto 4 Deoxyuronate Isomerase (KduI) nach Fütterung der kaseinhaltigen Diät herunterreguliert wurden. Mittels Reportergenanalysen wurde gezeigt, dass Galakturonat und Glukuronat die kduD und kduI Expression induzierten. KduI begünstigte die Umsetzung dieser Hexuronate. In E. coli wird die Umsetzung von Galakturonat und Glukuronat typischerweise von den Enzymen Uronate Isomerase (UxaC), Altronate Oxidoreduktase (UxaB), Altronate Dehydratase (UxaA), Mannonate Oxidoreduktase (UxuB) und Mannonate Dehydratase (UxuA) katalysiert. Weitere Experimente verdeutlichten, dass osmotischer Stress die Expression der Gene uxaCA, uxaB und uxuAB verminderte. Darüber hinaus zeigten kduID defiziente E. coli Mutanten in Gegenwart von Galakturonat oder Glukuronat und durch Saccharose ausgelösten osmotischen Stress eine Verlangsamung des Wachstums. Das deutet darauf hin, dass KduI und KduD die durch osmotischen Stress bedingten Funktionseinschränkungen der regulären hexuronatabbauenden Enzyme kompensieren. Die beobachtete Bildung von intrazellulären Hexuronaten während des Laktosekatabolismus in vitro stellt eine Verbindung zu dem ursprünglichen Tierexperiment her und deutet darauf hin, dass der Ernährungsfaktor Laktose die Verfügbarkeit von Hexuronat für intestinale E. coli beeinflusst. Diese Studie weist somit den Einfluss von osmotischem Stress auf die Expression von OxyR abhängigen Genen, die für Stressantwortproteine sowie für metabolische Enzymen kodieren, in E. coli nach. Durch Nahrungsfaktoren entstandener osmotischer Stress stellt demnach einen entscheidenden Faktor für die bakterielle Kolonisation des Darmes dar.
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Johnson, Andrew M. F. "The characterisation of intestinal dendritic cells and the control of immune responses towards the microbiota." Thesis, University of Oxford, 2011. http://ora.ox.ac.uk/objects/uuid:14284c3c-1aa4-4125-ad31-e74ded4e75bc.
Анотація:
Dendritic cells (DCs) are regulators of the immune response and are thought to be critical in maintaining tolerance towards the intestinal microbiota. Recent data have identified distinct subsets of DCs with specific functional properties. The objective of this thesis was to further define CD103⁺ and CX3CR1⁺ DCs in the intestine and to determine how DCs and regulatory T (Treg) cell responses are influenced by the microbiota. Using multicolour flow cytometry, we identified two CD103⁺ DC subsets with differential aldehyde dehydgrogenase (ALDH) activity and two populations of CX3CR1⁺ cells. In the mesenteric lymph node CD103⁺ALDH⁺ DCs were highly mature (CD86hi, MHCIIhi), likely migratory (CCR7⁺) and enhanced Treg cell induction compared with ALDH⁻ DCs. CX3CR1int cells accumulated during bacterially-induced colitis suggesting a pro-inflammatory role whereas CX3CR1hi cells were associated with the production of the anti-inflammatory cytokine IL-10 during homeostasis. We also assessed the generation of CD103⁺ DCs from bone marrow progenitors. Although only small proportions of CD103⁺ DCs were detected in culture with FLT3L or GM-CSF alone, the combination of FLT3L and GM-CSF induced CD103⁺ DCs with a phenotype similar to those found in the small intestine. Using this system we showed that TLR ligands and retinoic acid induce ALDH enzyme activity in vitro. In order to assess how DCs and Treg cells respond to changes in the microbiota we employed broad-spectrum antibiotic treatment to deplete endogenous bacteria and also analyzed the impact of colonization with the model organism Helicobacter hepaticus. Interestingly, we did not detect alterations in the proportions of different DC subsets following antibiotic treatment or H. hepaticus infection. However, using a novel FoxP3huCD2-IL-10GFP reporter mouse, we found that IL-10 production by Treg cells was ablated following antibiotic treatment and significantly elevated following H. hepaticus infection. Preliminary investigation of the mechanism underlying this effect suggests a role for IL-27. In summary, this thesis provides further detail on the phenotype of intestinal DCs and shows that Treg cell IL-10 production is sensitive to the composition of the microbiota.
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PAULINO, Barbara Costa. "Consequências do uso de soro de leite de cabra sobre parâmetros bioquímicos, morfologia e microbiota fecal de ratas e filhotes jovens alimentados com dieta ocidentalizada desde a vida perinatal." Universidade Federal de Pernambuco, 2016. https://repositorio.ufpe.br/handle/123456789/18453.
Анотація:
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CNPQ
A dieta ocidentalizada, rica em lipídeos, açúcar, sódio e alimentos processados e ultra processados tem sido apontada como um dos mais relevantes fatores associados ao excesso de peso/obesidade, comorbidades e distúrbios fisio-metabólicos observados em estudos epidemiológicos e experimentais em animais. O objetivo do presente estudo foi investigar os efeitos do soro de leite de cabra sobre o estado nutricional, microbiota, histologia intestinal e parâmetros bioquímicos de ratas e filhotes alimentados com dieta ocidentalizada. Foram utilizados 8 machos e 24 fêmeas da linhagem Wistar (da colônia do Departamento de Nutrição da Universidade Federal de Pernambuco) para o acasalamento dos animais. Ratas gestantes foram divididas em quatro grupos experimentais de acordo com a dieta: Controle ou Ocidentalizada e a suplementação ou não com soro de leite de cabra. Evolução ponderal e consumo alimentar das ratas seguiram por todo experimento. Ao desmame, as ratas e metade da prole de machos de cada ninhada foram eutanasiados para análise dos parâmetros bioquímicos, histologia intestinal, micro-organismos fecais. Metade dos filhotes foi submetida aos mesmos acompanhamentos e eutanasiados aos 45 dias de vida. A suplementação com soro de leite de cabra modificou poucos parâmetros nas ratas com exceção da alteração da quantidade de lactobacilos totais, que nos grupos controles com solução salina apresentaram uma média de 7,34±0,08 log.UFC/g-1 e 6,43±0,31 log.UFC/g-1 e no suplementado 7,79±0,30 log.UFC/g-1 e 6,94±0,45 log.UFC/g-1 para ratas com dieta ocidentalizada e padrão, respectivamente. Nos filhotes, a suplementação com soro de leite de cabra promoveu redução no ganho de peso e dos depósitos de gordura abdominal, alteração bioquímica, aumentou em 15% a contagem de lactobacilos e em 13% as enterobactérias. Além disso, minimizou o desgaste de células intestinais, limitando o processo inflamatório observado nos alimentados com dieta ocidentalizada. Dessa forma, pode-se sugerir que o soro de leite teve potencial efeito na microbiota fecal e morfologia intestinal, e que esses efeitos parecem depender da idade e do período de suplementação.
The westernized diet rich in fat, sugar, sodium and processed foods and processed ultra has been identified as one of the most important factors associated with overweight / obesity, comorbidities, and physiological and metabolic disorders observed in epidemiological and experimental studies in animals. The aim of this study was to investigate the effects of serum of goat milk on the nutritional status, microbiota, intestinal histology and biochemical parameters of rats and offispring fed westernized diet. Were used 8 male and 24 female Wistar (the colony of the Department of Nutrition at the Federal University of Pernambuco) for mating of animals. Pregnant rats were divided into four groups according to the diet: control or Westernized and supplemented or not with serum from goat milk. weight gain and food consumption of rats followed throughout the experiment. At weaning, rats, half male offspring in each litter were sacrificed for analysis of biochemical parameters, intestinal histology, faecal micro-organisms. Half of the pups was subjected to the same accompaniments and euthanized at 45 days of life. Supplementation with goat whey modified few parameters in rats with the exception of changing the amount of total lactobacilli that in control groups with saline had a mean of 7,34 ± 0,08 log.UFC/g-1 and 6, 43 ± 0,31 log.UFC/g1 and supplemented 7,79±0,30 log.UFC/g-1 and 6,94 ± 0,45 log.UFC/g-1 to rats with westernized diet and standard, respectively. In puppies, supplementation with goat whey promoted reduction of 200% in weight gain and deposits of abdominal fat, biochemical change, increased by 15% to lactobacillus count and 13% enterobacteria. In addition, minimized wear of intestinal cells by limiting the inflammatory process observed in fed westernized diet. Thus, it can be suggested that the whey had potential effect on fecal microbiota and intestinal morphology, and that these effects appear to depend on the age and supplementation period.
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Milard, Marine. "Effets métaboliques des lipides polaires laitiers : mécanismes associés à la régulation de la barrière intestinale et effets spécifiques de la sphingomyéline in vitro." Thesis, Lyon, 2019. http://www.theses.fr/2019LYSE1007.
Анотація:
Les lipides polaires (LP) laitiers (~2% des lipides du lait) présentent un potentiel bioactif élevé, notamment lié à leur richesse en sphingomyéline (SM, ~25% des LP). Nos hypothèses sont que les LP laitiers peuvent exercer certains de leurs effets bénéfiques par l'intermédiaire de la SM, notamment sur l'intégrité de la barrière intestinale et le microbiote, ce qui pourrait contribuer à réduire l'inflammation métabolique. Nous avons testé à long terme in vivo l'impact de régimes hyperlipidiques (HF) supplémentés en LP laitiers. In vitro, nous avons étudié l'effet des LP laitiers et de la SM (laitière ou d'oeuf) sur l'expression génique des protéines de jonctions serrées. Nos travaux in vitro ont également permis de tester que l'interleurkine-8 (IL-8), impliquée dans la maturation de l'épithélium intestinal, serait un acteur des modifications intestinales en réponse aux LP laitiers et/ou à la SM. L'impact à court terme d'un gavage chez la souris avec des LP laitiers ou de la SM laitière a également été étudié. Après 8 semaines de régime HF supplémenté en LP laitiers (1,6%) les souris présentent un moindre gain de poids en comparaison au régime HF. Nous observons une augmentation de Bifidobacterium animalis pour le groupe contenant 1,1% de LP laitiers. Le groupe nourri avec une supplémentation de 1,6% de LP laitiers présente une diminution de Lactobacillus reuteri et des cryptes coliques plus profondes. Nous retrouvons également une plus forte teneur en acide gras spécifiques des LP laitiers (C23:0, C24:0 et C24:1, présents dans la SM laitière) dans les lipides fécaux. Ces acides gras sont corrélés à la teneur en Lactobacillus spp. Parmi les protéines de jonctions serrées impliquées dans la perméabilité paracellulaire, seule l'expression de ZO-1 tend à être augmentée dans le duodénum. In vitro, lorsque les cellules Caco-2/TC7 sont incubées avec des micelles mixtes supplémentées en SM pure, une augmentation de l'expression génique des protéines de jonctions serrées, ainsi qu'une augmentation de la concentration d'IL-8 en apicale et en basolatérale, sont observées. Ces effets sont également retrouvés avec la SM d'oeuf, contrairement aux LP laitiers totaux. L'incubation d'IL-8 recombinante humaine conduit à une augmentation de l'expression génique des protéines de jonctions serrées. Un gavage avec de la SM laitière pure chez la souris induit une augmentation de l'expression des homologues murins de l'IL-8 (KC et Mip-2). Cette étude suggère que les LP laitiers peuvent limiter la prise de poids induite par un régime HF et moduler le microbiote intestinal. La présence de produits d'hydrolyse spécifiques de la SM pourrait expliquer les effets sur le côlon et le microbiote intestinal. Les résultats in vitro, suggèrent un impact spécifique de la SM sur la barrière intestinale. L'IL-8 semble impliquée dans la régulation de l'expression des protéines de jonctions serrées. Ces résultats contribuent à expliquer les effets bénéfiques démontrés des LP laitiers. L'exploration mécanistique des effets directs et/ou indirects de la SM et de l'IL-8 sur la barrière intestinale reste à éluciderInterest is growing for the metabolic impact of milk polar lipids (MPL, ~2% of dairy lipids), which present a high bioactive potential, particularly related to their content in sphingomyelin (SM, ~ 25% of MPL). Our hypotheses are that MPL can exert some of their beneficial effects through SM, including the integrity of the intestinal barrier and the microbiota, which could contribute to reduce metabolic inflammation. We tested the metabolic impact of the addition of MPL in a high-fat (HF) diet in mice on the modulation of the intestinal barrier. In vitro, we studied the effect of SM (milk or egg) on tight junction protein We also tested in vitro, that interleurkin-8 (IL-8), which is involved in the maturation of the intestinal epithelium, is an actor of intestinal changes in response to MPL and/or MSM. The short-term impact in mice of MPL or milk SM was also studied. After 8 weeks of diet, the supplementation with 1.6% of MPL prevented the HF-diet-induced body weight gain. In caecal microbiota, addition of 1.1% of MPL induced a specific increase in Bifidobacterium spp., in particular B. animalis. The group fed with a 1.6% MPL-supplementation showed a specific decrease in Lactobacteria reuteri and colonic crypt depth were greatest. We also found a higher content of fatty acids specific of MPL (C23:0, C24:0 and C24:1, found in milk SM) in fecal lipids of mice. These fatty acids are correlated with Lactobacillus spp. Among the tight junction proteins involved in paracellular permeability, only the expression of ZO-1 tended to be increased in the duodenum. In vitro, when Caco-2/TC7 cells were incubated with mixed micelles supplemented with pure SM, an increase in the gene expression of tight junction proteins (ZO-1, occludin, JAM-1, claudin-1) and an increase in apical and basolateral IL-8 concentration were observed. These effects were also found with egg SM, unlike total MPL. Incubation of recombinant human IL-8 led to an increase in gene expression of tight junction proteins. Gavage with pure milk- SM in mice induced an increase in the expression of murine homologs of IL-8 (KC and Mip-2). Our results show that MPL can limit HF-induced body weight gain and modulate the abundance of beneficial bacteria of the gut microbiota. The presence of SM-specific hydrolysis products may explain the effects on the colon and gut microbiota. In vitro results suggest a specific impact of pure SM on the intestinal barrier. IL-8 appears to be involved in the regulation of tight junction protein expression. This can contribute to explain reported beneficial effects of MPL in mice regarding HF induced metabolic disorders. The mechanistic exploration of direct and / or indirect effects of SM and IL-8 on the intestinal barrier remains to be elucidated
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Ghezzal, Sara. "Rôles des lipides alimentaires sur l'intestin : métabolisme, inflammation et fonction de barrière." Thesis, Sorbonne université, 2018. http://www.theses.fr/2018SORUS436.
Анотація:
L’origine de l’inflammation systémique présente à un niveau subclinique chez les sujets obèses est mal connue. Des données suggèrent la participation de l’intestin et des lipides dans l’initiation de cette inflammation. L’objectif de ma thèse a été de déterminer si un apport à court terme de lipides, en particulier d’acide palmitique, pouvait conduire à des altérations de la barrière intestinale, qui en retour faciliteraient le passage de fragments bactériens, activant le système immunitaire localement et en systémique. J’ai étudié chez la souris l’impact d’un apport aigu ou répété d’huile de palme sur l’intégrité de la barrière intestinale, l’expression de marqueurs inflammatoires et le microbiote. Mes travaux montrent qu’un apport unique d’acides gras saturés suffit à perturber la barrière épithéliale intestinale et à moduler localement l’expression de cytokines pro-inflammatoires. La répétition d’un tel apport exacerbe ces effets et modifie l’abondance des bactéries intestinales. Le rôle de l’acide palmitique a été analysé dans la lignée cellulaire Caco-2/TC7. J’ai montré que ces effets délétères s’exercent indépendamment du microbiote et des cellules immunitaires et impliquent la voie de synthèse de novo des céramides. Ces résultats ouvrent la voie à de nouvelles études qui permettront de préciser les mécanismes moléculaires mis en place en réponse aux lipidesThe origin of systemic inflammation observed at a subclinical level in obese patients is still unclear. Studies suggest the participation of the intestine and dietary lipids in the onset of inflammation. The aim of my thesis was to determine whether a short-term lipid supply, rich in saturated fatty acid, could compromise the intestinal barrier integrity, which could in turn increase the endotoxin passage through the intestinal mucosa, activate the immune system and trigger local or systemic inflammation. In mice, I studied the effect of a single or repeated supply of palm oil on intestinal barrier integrity, inflammatory markers and microbiota. My results showed that a single supply of palm oil is sufficient to alter intestinal epithelial barrier and to modulate in the intestine the expression of pro-inflammatory cytokine. A repeated supply exacerbates these deleterious effects and modifies the abundance of intestinal bacteria. The role of palmitic acid was analyzed on a polarized monolayer of the human intestinal epithelial cell line, the Caco-2/TC7 cells. The results indicated that the deleterious effects could be exert independently of microbiota and immune cell interactions and involved the de novo ceramide synthesis pathway. Altogether, my results pave the way for further studies aiming at specifying the various cellular processes in response to dietary lipids
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Clark, Jessica Ann. "The Protective Role of Epidermal Growth Factor in Neonatal Necrotizing Enterocolitis." Diss., The University of Arizona, 2006. http://hdl.handle.net/10150/195517.
Анотація:
Neonatal necrotizing enterocolitis (NEC) is the most common gastrointestinal disease in premature babies. Despite significant morbidity and mortality, the cause of this disease remains unclear and there are no preventative treatments available. Prematurity and enteral feeding of infant formula are considered to be the primary risk factors for development of NEC. Interestingly, the incidence of NEC is six to ten times lower in breast-fed babies compared to those that were formula-fed. The factors responsible for the protective effect of breast milk against NEC have not been identified, but epidermal growth factor (EGF) is one of the most promising candidates. EGF is found at high concentrations in human milk, but is not present in any commercial formula. Mothers with extremely premature babies have 50-80% higher levels of EGF in their breast milk compared to mothers with full term infants. This suggests that EGF plays an important role in the development of premature infants. Our studies have shown that supplementation of EGF into formula significantly reduces the incidence of NEC in a neonatal rat model. However, the mechanisms underlying this EGF-mediated reduction of NEC are not understood. The overall hypothesis of this dissertation is that the protective effect of EGF in NEC pathogenesis is mediated via increased expression of pro-survival genes and strengthening of the mucosal barrier. The results of the studies within this dissertation demonstrate that treatment with EGF significantly decreases intestinal epithelial cell apoptosis at the site of NEC injury by up-regulating anti-apoptotic genes and down-regulating pro-apoptotic genes. Furthermore, supplementation of formula with EGF strengthens the mucosal barrier by inducing accelerated maturation of ileal goblet cells and mucin-2 production. In addition, EGF treatment normalizes expression of crucial tight junction proteins in the ileum. Consequently, EGF treatment results in a significant decrease in intestinal paracellular permeability and improved barrier function. Results from these studies will provide significant contributions to the understanding of EGF-mediated reduction of NEC, which may lead to development of therapeutic strategies for the treatment of human NEC.
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Merino, Juan Jiménez. "Circulatory stem cells of Styela plicata (Lesueur, 1823) (Tunicata: Stelidae): an evolutionary approach." Universidade de São Paulo, 2018. http://www.teses.usp.br/teses/disponiveis/41/41133/tde-18022019-090152/.
Анотація:
Styelid ascidians are diverse in developmental modes, varying from strictly sexual solitary species to highly integrated colonies. Circulatory stem cells (CSCs) accomplish fundamental roles in developmental processes of styelid ascidians. In the colonial styelids, CSCs enable budding and are capable of giving origin to the germline in certain species. The function of these cells have been tested experimentally in models within Styelidae. However, the understanding of coloniality as an evolutionary novelty requires reconstructing the possible ancestral CSCs characteristics in Styelidae. To address this issue, this work analyzes the possible developmental origin and the identity of putative CSCs among blood cell populations. The first chapter of this dissertation aimed to characterize and compare the hemocyte populations in two solitary styelids: Styela plicata and Styela canopus. In addition, the early development, the metamorphosis and the early maturation were compared in both species. After metamorphosis, S. canopus briefly develops a network of extracorporeal vessels with numerous terminal ampullae. These characters are usually associated to colonial ascidians, and were not found in S. plicata. With respect to the hemocyte populations, similar morphotypes were present in both species. However, S. canopus shows a lower frequency of vacuolated cells, which may be due to a reduced level of cytotoxicity in the tunic relative to S. plicata. These differences observed between S. canopus and S. plicata may be related to differences in the degrees of gregariousness or body size among the two species. In order to investigate possible approaches to distinguish and isolate CSC populations in a solitary styelid model, I used imaging flow cytometry. Putative CSCs were identified through measurement of morphological parameters and aldehyde dehydrogenase (ALDH) activity. The correlation between these parameters allowed to determine 2 gates enriched with particular cell types. A significant difference was found on the ALDH+ population within a gate of cells with low granularity, suggesting the presence of cells among circulatory hemocytes. To scrutinize the biogenesis of CSCs in S. plicata, I present a description of a candidate hematopoietic niche in this species. An exhaustive histological survey for hemoblast-like cells was performed, and complemented with immunohistochemistry with stem cell (piwi) and proliferation (pHH3) markers. The morphological and expression profiles of the intestine support the intestinal submucosa (IS) as a hematopoietic niche. At this region there are aggregations of cells with and undifferentiated morphological profile, corroborated by ultrastructural analysis. Furthermore, the IS holds high cellular proliferation and frequency of piwi+ cells. Ascidians are considered interesting models to investigate asexual reproduction and modular development. This study represents an advancement towards understanding the processes, cell populations and structures that may be related to facilitating the appearance of this evolutionary noveltyAs ascídias da família Styelidae são diversas em modos de desenvolvimento, variando de espécies estritamente sexuais solitárias até colônias altamente integradas. As células-tronco circulatórias (CTCs) desempenham papéis fundamentais nos processos do desenvolvimento de ascídias styelídeas. Nas especies coloniais deste grupo, as CTCs permitem a brotação e são capazes de originar a linha germinativa em certas espécies. A função dessas células tem sido testada experimentalmente em modelos dentro de Styelidae. No entanto, a compreensão da colonialidade como uma novidade evolutiva requer reconstruir as características das possíveis CTCs ancestrais para Styelidae. Com o fim de abordar essa questão, este trabalho analisa a possível origem do desenvolvimento e a identidade de CSCs putativas entre populações de células sanguíneas de styelídeas solitárias. O primeiro capítulo desta dissertação teve como objetivo caracterizar e comparar as populações de hemócitos em dois espécies solitárias: Styela plicata e Styela canopos. Além disso, o desenvolvimento inicial, a metamorfose e a maturação do juvenil foram comparados em ambas as espécies. Após a metamorfose, S. canopus desenvolve brevemente uma rede de vasos extracorpóreos com numerosas ampolas terminais. Esses caracteres são geralmente associados a ascídias coloniais e não foram encontrados em S. plicata. Com relação às populações de hemócitos, morfotipos semelhantes estavam presentes em ambas as espécies. No entanto, o S. canopos apresenta menor frequência de células vacuoladas, o que pode ser devido a um nível reduzido de citotoxicidade na túnica em relação a S. plicata. Essas diferenças observadas entre S. canopos e S. plicata podem estar relacionadas a diferenças nos graus de gregariedade ou tamanho corporal entre as duas espécies. A fim de investigar possíveis abordagens para distinguir e isolar populações de CTCs em um modelo de styelídeo solitário, usei citometria de fluxo com adquisição de imagem. As CTCs putativas foram identificadas através da medição de parâmetros morfológicos e da atividade da aldeído desidrogenase (ALDH). A correlação entre estes parâmetros permitiu determinar 2 gates enriquecidos com tipos celuláres particulares. Uma diferença significativa foi encontrada na população ALDH+ dentro de um gate de células com baixa granularidade, sugerindo a presença de células-tronco circulatórias. Para examinar a biogênese das CTCs em S. plicata, foi realizada uma descrição de um nicho hematopoiético candidato nesta espécie. Um exame histológico exaustivo para células semelhantes a hemoblastos foi realizado e complementado com imunohistoquímica com marcadores de células-tronco (piwi) e proliferação (pHH3). Os perfis morfológicos e de expressão do intestino sustentam a submucosa intestinal (SI) como nicho hematopoiético. Nesta região há agregações de células com morfolia indiferenciada, corroborada pela análise ultraestrutural. Além disso, a SI mantém alta proliferação celular e freqüência de células piwi+. As ascídias são consideradas modelos interessantes para investigar a reprodução assexuada e o desenvolvimento modular. Este estudo representa um avanço na compreensão dos processos, populações celulares e estruturas que podem estar relacionadas a facilitar o surgimento desta novidade evolutiva
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Bernis, Filho Walter Octaviano. "Estudo comparativo da cicatrização entre os fios poliglecaprone, algodão e poliglactina em anastomoses de intestino delgado de cães." [s.n.], 2010. http://repositorio.unicamp.br/jspui/handle/REPOSIP/311383.
Анотація:
Orientador: Nelson Adami AndreolloTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: Através dos anos muitos fios de sutura foram criados e, depois abandonados, em virtude dos bons resultados obtidos com novos fios. Ainda sim, até hoje não se encontrou um fio cirúrgico totalmente inócuo ao intestino, ou a outros tecidos de um modo geral, tornando sua escolha uma tarefa difícil. Justifica-se, a necessidade de pesquisa de novos materiais no intuito de se encontrar a opção ideal. Neste trabalho foi testado o fio poliglecaprone 25, nas anastomoses do intestino delgado de cão comparando com fios, tradicionalmente usados por outros autores na confecção de anastomoses intestinais, como os fios algodão e poliglactina 910. A cicatrização de anastomoses do intestino delgado foi avaliada, macroscópica e microscópicamente, utilizando três tipos de sutura distintos com os fios poliglecaprone 25, poliglactina 910 e o algodão. Vinte cães machos sem raça definida pesando entre 9 e 16 Kg foram submetidos, após anestesia geral inalatória, a três anastomoses no intestino delgado. A técnica empregada foi a extramucosa com pontos separados e utilizou-se, para cada uma, os fios poliglecaprone 25, a poliglactina 910 e o algodão. Os animais foram separados em 4 grupos de acordo com a avaliação do período pós-operatório: grupoI- 3 dias; grupoII- 7 dias; grupoIII- 14dias; grupo IV- 21dias. Após o período de observação, os animais foram submetidos a eutanásia para coleta de material para análise macroscópica e microscópica. Na avaliação macroscópica os três fios se comportaram bem, com boa coaptação das bordas, porém com moderado grau de aderência entre alças e epiploo, do 3º ao 21º dia do pós-operatório. A avaliação microscópica mostrou inflamação exsudativa com neutrófilos e fibrina que variou de discreta a moderada até o 14º dia; inflamação granulomatosa com presença de macrófagos, células gigantes multinucleadas e células epitelióides mais evidente ao 14º dia para o fio algodão; presença de tecido de granulação (fibroblastos) e fibras colágenas, de forma moderada, a partir do 7º dia para os três fios. Os três tipos de fios de sutura utilizados nesta pesquisa apresentaram comportamento semelhante e podem ser indicados em anastomoses do intestino delgado
Abstract: In this study was evaluate, macroscopically and microscopically, the healing process of intestinal anastomoses in dogs using polyglecaprone 25, polyglactin 910 and cotton sutures. Twenty mongrel dogs, weighting from 9 to 16 Kg were submitted, under general inhalatory anesthesia, to three small intestine anastomoses. The animals were divided into four groups, in accordance with the postoperative observation periods as follows: group I, three days; group II, seven days; group III, fourteen days; group IV, twenty one days. Extramucous technique was used, with those threads, in all four groups. After the observation period the animals were euthanized and samples from the operative site were collected for macroscopic and microscopic evaluations. Macroscopically, all three threads showed good behavior with good coaptation of the edges; however, there occurred a moderate level of adherence between loops of intestine and omentum, from day 3 to day 21, of postoperative period. Microscopically, there was exsudative inflammation, with neutrophils and fibrin, discrete to moderate until day 14. Granulomatous inflammation was also notice accompanied by macrophages, multinucleated giant cells and epithelioid cells, more evident on day 14 in the cotton group. Granulation tissue (fibroblasts) and collagen fibers were also observed, in a moderate pattern, for all three suture materials, from day 7. All three suture threads used in this research showed similar behavior and thus they can be indicated for anastomoses of the small intestine in dogs
Doutorado
Fisiopatologia Cirúrgica
Doutor em Ciências
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Castro, Leonardo Maggio de. "Avaliação de nova técnica de biopsia intestinal assistida por videolaparoscopia em equinos." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/10/10137/tde-14092016-125244/.
Анотація:
As doenças do trato digestório nos equinos apresentam altas taxas de morbidade e mortalidade, com diferentes etiologias. Em alguns casos, o emprego da biopsia intestinal se faz necessário para auxílio no diagnóstico dessas enfermidades. No entanto, as técnicas convencionais podem trazer riscos aos pacientes, por serem invasivas, ou não serem elucidativas por apresentarem limitações de acesso a determinados segmentos. O presente estudo teve como objetivo validar uma técnica de biopsia intestinal, intracorpórea, assistida por videolaparoscopia, ainda não descrita na literatura, para coleta de fragmentos de mucosa de jejuno e cólon menor de equinos, que sejam considerados adequados para avaliação histológica. Para tanto, foram utilizados seis equinos machos, da raça Puro Sangue Árabe, com idade de dois anos, sem histórico prévio de doenças do trato digestório, com peso médio de 267 kg. Todos os animais foram submetidos ao mesmo procedimento laparoscópico, instituindo-se apenas jejum alimentar prévio de oito horas. Os equinos foram acompanhados com exame físico e de ultrassonografia abdominal, desde o dia precedente às laparoscopias, até o 15º dia do período pós-operatório, bem como avaliados por meio de hemograma, provas de funções hepática e renal, e análise do líquido peritoneal nos dias 0, 1, 2, 3, 5, 7, 10, 14, 21 e 30. O tempo cirúrgico foi cronometrado, sendo registrado o tempo total, iniciado na criação do primeiro portal de acesso e finalizado ao término da sutura de pele, e os tempos parciais para biopsia de jejuno e cólon menor separadamente, com início na apreensão do segmento intestinal e término quando constatada a polimerização da cola cirúrgica sobre o orifício de acesso da agulha. De cada segmento obtiveram-se dez fragmentos, e posteriormente submetidos à análise histológica. Atribuiu-se escore para cada um deles, sendo considerado 0 fragmentos com qualidade ruim; 1 para qualidade boa e 2 para qualidade ótima. Por sua vez, os considerados viáveis foram somente os que se enquadraram nos escores 1 e 2. Amostras avaliadas como adequadas 11 apresentaram no mínimo 50% dos fragmentos viáveis. A média do tempo total de procedimento foi de 66,50 minutos (± 7,87), enquanto a média do tempo parcial para biopsia de jejuno foi de 14,2 minutos (± 4,3) e a de cólon menor 12,7 minutos (± 5,0). Clinicamente, os animais apresentaram desconforto abdominal nas primeiras 48 horas. Os exames ultrassonográficos do abdômen não revelaram alterações condizentes com peritonite ao longo de todo experimento. Os parâmetros laboratoriais apresentaram apenas características inflamatórias, sendo que o líquido peritoneal permaneceu alterado até o 21º de pós-operatório, havendo normalização de todos os seus valores no 30º dia do estudo. Na inspeção laparoscópica de dois equinos (E2, E4) foi identificada aderência de porção de omento no diafragma. Nas avaliações histológicas de jejuno, uma amostra (E5) de seis foi considerada inadequada, com 5/12 fragmentos viáveis, e em cólon menor, duas (E1, E2) de seis, foram inadequadas, com 4/9 e 5/10 fragmentos viáveis respectivamente. A nova técnica de biopsia intestinal possibilitou a coleta de amostras adequadas de mucosa para análise histológica, de forma segura para os animais, uma vez que as alterações clínicas e laboratoriais foram aquelas relacionadas ao processo inflamatório, compatível com procedimentos laparoscópicos na espécieGastrointestinal diseases in horses result in high rates of morbidity and mortality, with different aetiologies. In some cases, an intestinal biopsy is needed to aid in the diagnosis of such diseases. However, the conventional techniques can pose risks to patients for being invasive or for not being elucidating due to having limitations in accessing certain segments. The objective of this study was to validate an intestinal biopsy technique, intracorporeal, assisted by laparoscopy, which has not yet been described in the literature, to collect mucosal fragments from the jejuno and small colon, which might be considered suitable for histological assessment. For such, six male horses were used, Arabian breed, with two years of age, without any records of abdominal diseases, weighing 267 kg in average. All horses were subjected to the same laparoscopic procedure, fasting for eight hours previously to the procedure. All horses were monitored through physical examination and abdominal ultrasonography, from the day previous to laparoscopy, until the 15th postoperative day, as well as hemogram, tests of liver and kidney functions, and analysis of the peritoneal fluid in days 0, 1, 2, 3, 5, 7, 10, 14, 21 and 30. The total laparoscopic procedure time was registered, starting at the moment of the first incision and ending at the moment of the skin closure. The partial times for the jejunal biopsy and small colon biopsy were recorded as well, starting at the grasping of the intestinal segment and ending at the moment of polymerization of the surgical adhesive on the needle access site. From each segment, ten fragments were collected and later subjected to histological analysis. A score was assigned for each one of them, being scored \"0\" fragments of poor quality; \"1\" fragments of good quality and \"2\" fragments of optimal quality. The samples considered viable were only the ones which scored 1 and 2. The samples deemed as adequate showed at least 50% of it fragments to be viable. The average of the surgery total time was of 66,50 minutes (± 7.87), whereas the average of the jejunal biopsy was of 14.2 minutes (± 4.3) and the small colon biopsy time was of 12.7 minutes ( ± 5.0). Clinically, the animals showed mild abdominal 13 discomfort in the first 48 hours. Ultrasonographic examination of the abdomen did not reveal any alterations consistent with peritonitis throughout the entire experiment period. Laboratory parameters presented inflammatory characteristics, and the peritoneal fluid remained altered until the 21th postoperative day, with normalization of all its values on the 30th day of the study. During the laparoscopic inspection of two horses (E2, E4) was identified partial omental adhesion with the diaphragm. In the jejunal histological evaluations, one sample (E5) of six was considered inadequate, with 5/12 viable fragments, and as for the small colon, two (E1, E2) of six were inadequate, with 4/9 and 5/10 viable fragments respectively. The new technique proposed allowed a safe collection of adequate mucosal samples for histological analysis, since clinical and laboratory abnormalities identified were related to the inflammatory process associated to the laparoscopic techniques in horses
15
Alvarenga, Mariana Lindenberg. "Cinética na absorção intestinal de [14C]-glutamina em camundongos saudáveis e submetidos à endotoxemia." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/9/9132/tde-02092013-110000/.
Анотація:
Os diversos estudos com a suplementação de glutamina em situações de estresse fisiológico demonstram o essencial papel deste aminoácido no metabolismo. Agudamente, a suplementação com glutamina aumenta a glutaminemia. Cronicamente, verifica-se maior concentração de glutamina em tecidos, tais como o muscular e o hepático. Entretanto, não é conhecido se esses efeitos são decorrentes diretos da suplementação oral com glutamina ou da redução de sua captação a partir da membrana basolateral de enterócitos. O estudo da cinética na absorção de glutamina traz informações relacionadas à proporção da concentração de glutamina absorvida e a retida no tecido intestinal, de acordo com as doses utilizadas, e aponta quais são as alterações decorrentes da sepse induzida pela endotoxemia. O objetivo deste trabalho foi investigar a cinética de absorção de glutamina em camundongos submetidos à endotoxemia, o que não fora previamente investigado em outros trabalhos. Para avaliar a cinética da absorção intestinal de glutamina foi realizada eversão intestinal em camundongos machos, o que permite a coleta dos líquidos das camadas mucosa e serosa com maior precisão. Foram utilizadas doses de 10, 20, 40 e 50 mM de L-glutamina associada a [14C]-glutamina, nos tempos 0, 5, 10, 20, 30, 40, 60, 90 e 120 minutos. Os resultados obtidos demonstraram que em alta concentração de glutamina (50 mM) ocorre maior absorção em relação à retenção tecidual e esta é realizada por transporte ativo de aminoácidos. Os animais que foram submetidos à endotoxemia por LPS (5mg/kg) apresentaram alterações estruturais no tecido intestinal, detectadas pela histologia. Neste grupo, a retenção tecidual de glutamina foi significativamente maior do que no grupo controle, sobretudo na presença de glicose. Conclui-se que a cinética na absorção de glutamina é dose e tempo dependente em animais saudáveis e que, em condições de endotoxemia, ocorre maior retenção de glutamina no tecido intestinal na presença de glicose. Sugere-se que a via da hexosamina está envolvida; no entanto, mais estudos são necessários para esclarecer tais mecanismos.The various studies of glutamine supplementation in stressful situations demonstrate the physiological role of this essential amino acid in metabolism. Acutely, supplementation with glutamine improves glutaminemia. Chronically, there is a greater concentration of glutamine in tissues such as muscle and liver. However, it is not known whether these effects are direct result of glutamine oral supplementation or reduced uptake within the basolateral membrane of enterocytes. The kinetic study of the absorption of glutamine provides information related to the ratio of concentration of glutamine absorbed and retained in the intestinal tissue, according to the doses used, and points out the changes resulting from sepsis induced by endotoxemia. The objective of this study was to investigate the kinetics of glutamine uptake in mice subjected to endotoxemia. To evaluate the kinetics of intestinal absorption of glutamine intestinal eversion was performed in male mice, allowing to collect the liquid layers of mucosa and serosa with greater precision. The doses used were 10, 20, 40 and 50 mM L-glutamine associated with [14C]-glutamine at 0, 5, 10, 20, 30, 40, 60, 90 and 120 minutes. The results showed that high concentrations of glutamine (50 mM) a higher absorption occurs in relation to tissue retention and this is accomplished by active transport of amino acids. The animals subjected to endotoxemia by LPS (5mg/kg) showed structural changes in the intestinal tissue, detected by histology. In this group, the tissue retention of glutamine was significantly higher than in the control group, especially in the presence of glucose. It is concluded that the kinetics of glutamine uptake is dose and time dependent in healthy animals, and in conditions of endotoxemia, there is greater retention of glutamine in intestinal tissue in the presence of glucose. It is suggested that the hexosamine pathway is involved; however, more studies are needed to clarify these mechanisms.
16
López, Arribillaga Erika 1986. "Notch signalling in intestinal homeostasis and cancer: orchestrator of stemness." Doctoral thesis, Universitat Pompeu Fabra, 2016. http://hdl.handle.net/10803/664090.
Анотація:
Wnt/β-catenin and Notch signalling cooperate in regulating the transcription of various genes specifically in the small intestinal stem and progenitor cell compartments. We characterized Bmi1 functionally in this context and showed that it contributes to ISC self-renewal capacity. We postulated that it does so by regulating its classical locus Cdkn2a and probably also by supporting DNA damage repair. Yet another level of Notch and Wnt/β-catenin crosstalk was found in colorectal cancer where tumour-associated β-catenin induced Jagged 1 (Jag1) transcription, thus leading to Notch activation. We also investigated which is the contribution of intestinal epithelial Jag1-mediated Notch activation on tumour initiating activity. We found that intestinal-specific deletion of Jag1 greatly decreases tumour formation in the ApcMin/+ background, likely due to reduced stemness. Jag1 deletion in preformed spheroids abrogates stemness-related gene expression and proliferation leading to spheroid failure. Jag1 is dispensable for normal stem cells, which rely on Dll1/4 Notch ligands for their maintenance. Together, these results open a new path in personalised CRC therapy, presumably involving Notch inhibition from specific ligands.Las vías de señalización de Wnt/β-catenina y de Notch cooperan en la regulación transcripcional de varios genes específicamente en las células madre / progenitoras del epitelio intestinal. Hemos caracterizado la funcionalidad de Bmi1 en este contexto y demostrado que contribuye a la capacidad de auto-renovación de las células madre intestinales. Postulamos que lleva a cabo esta función mediante la regulación de su diana clásica, Cdkn2a, pero probablemente también llevando a cabo funciones alternativas ayudando a la reparación del daño en el ADN. Sin embargo, existe otro nivel de cooperación entre las vías de señalización de Wnt/β-catenina y de Notch en el contexto del cáncer colorectal. Aquí, la β-catenina asociada al tumor es capaz de inducir la transcripción de Jagged1 (Jag1), resultando en la activación de la vía de Notch. También hemos investigado cuál es la contribución a la iniciación tumoral de la activación de Notch mediada por Jag1 epitelial. Encontramos que delecionando Jag1 específicamente en el epitelio intestinal se reducía la formación tumoral en el modelo animal ApcMin/+, probablemente debido a una pérdida de las características de célula madre. La deleción de Jag1 en esferoides previamente formados abroga la expresión de genes de célula madre y la proliferación, llevando al colapso de los esferoides. Jag1 es dispensable para las células madre normales, que dependen de los ligandos de Notch Dll1/4 para su supervivencia. En conjunto, estos resultados abren un nuevo camino a las terapias personalizadas en el tratamiento del cáncer colorectal, presumiblemente mediante la inhibición de Notch a partir de ligandos específicos.
17
Липовська, Вікторія Вікторівна, Виктория Викторовна Липовская, Viktoriia Viktorivna Lypovska, and Ahmed Heblo. "Action of epec and antibiotics on microflora of intestine of children with intestinal escherichiosis." Thesis, Видавництво СумДУ, 2010. http://essuir.sumdu.edu.ua/handle/123456789/6650.
Анотація:
Change of qualitative and quantitative structure contents of the microflora of intestines under influence Enteropathogenic E. coli (ЕРЕС) and antibiotic therapy on 98 children Sumy in the age 2 months till 8 years is investigated.
When you are citing the document, use the following link http://essuir.sumdu.edu.ua/handle/123456789/6650
18
Masjedi, Mohsen. "Physiological inflammation of the small intestine during weaning in the rat /." Title page, table of contents and summary only, 1998. http://web4.library.adelaide.edu.au/theses/09PH/09phm3973.pdf.
19
Thompson, Fiona Marie. "Activation of the mucosal immune system and growth of the small intestine at weaning /." Title page, abstract and contents only, 1994. http://web4.library.adelaide.edu.au/theses/09PH/09pht4677.pdf.
20
Dimas, Sophie Francis. "The response in the rat small intestine to infections of 5 and 50 cysticercoids of H. diminuta a morphometric study /." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0015/MQ56172.pdf.
21
Gray, Allison J. "Saccharomyces boulardii and the small intestine." Thesis, Queen's University Belfast, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.282154.
22
Hastewell, J. G. "Pyrimidine transport in rat small intestine." Thesis, University of York, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.373286.
23
Dosh, Rasha. "Developing models of the small intestine." Thesis, Sheffield Hallam University, 2018. http://shura.shu.ac.uk/24027/.
Анотація:
Inflammatory bowel disease (IBD) is a chronic autoimmune disease characterised by inflammation of the gastrointestinal tract. The pathogenesis of IBD is not fully understood and curative therapies are lacking. Consequently, development of robust intestine models, representative of the pathogenesis of IBD remains an unmet need. Thus, the overall aims of the studies presented in this thesis were to develop a number of models of small intestine including: genetically engineered murine model, epithelial cell culture models, and an intestinal stem cell organoid model which could reflect or be used to study the pathogenesis of IBD. Interleukin 1 (IL-1) is an important mediator of inflammation and tissue damage in IBD. The balance between IL-1 and IL-1Ra as a natural inhibitor plays a vital role in a variety of diseases. Here, this thesis investigated whether changes seen during IBD could be induced spontaneously by the removal of IL-1Ra in mice that lack a functional IL-1rn gene. Data presented from this thesis highlighted the importance of IL-1 in the pathogenesis of inflammatory bowel disease. In addition, the potential of L-pNIPAM hydrogel scaffolds, which were developed by the research team at Sheffield Hallam University, was utilised to develop long-term 3D co-cultures of layered Caco-2 and HT29-MTX cells under conditions representative of inflammation by treatment with IL-1β, TNFα, and hypoxia (1% O2) for 1 week was investigated. In vitro cell culture studies in this thesis have demonstrated that L-pNIPAM hydrogel supported long-term 3D co-culture model and stimulation with factors seen during inflammation recapitulated features of IBD. Finally, the potential of L-pNIPAM hydrogel scaffolds to develop 3D intestinal stem cell organoid model was investigated. The in vitro study demonstrated the ability of L-pNIPAM hydrogel as scaffold to support organoid formation and cell differentiation in vitro from small intestinal crypts and Lgr5+ stem cells isolated from mice.
24
Bravo, Blas Antonio Alberto. "Development of macrophages in the intestine." Thesis, University of Glasgow, 2014. http://theses.gla.ac.uk/5389/.
Анотація:
Macrophages (mφ) are one the most numerous leukocytes present in the healthy gut and contribute to both harmful and beneficial immune reactions. In the colon, mφ are exposed continuously to large amounts of material from the environment, including harmful agents such as invasive bacteria, viruses and parasites, as well as harmless materials such as food proteins and the commensal bacteria which inhabit the healthy intestine. As a result, mφ play an important role in helping defend the intestine against harmful invaders. However if these cells make similar reactions to harmless food proteins or commensal bacteria, it would be both wasteful and detrimental, likely leading to inflammatory diseases such as coeliac disease and Crohn’s disease. Several genes, which underlie susceptibility to Crohn’s disease are involved in controlling how macrophages respond to the microbiota, with considerable evidence indicating that this reflects a loss of the normal unresponsiveness that characterises intestinal macrophages in the healthy intestine. One of the most significant aspects of the epidemiology of Crohn’s disease is a particularly rapid increase in its incidence in childhood, suggesting that the first encounters between the microbiota and intestinal macrophages may be of critical importance in determining disease susceptibility. Given this link, it is essential that we elucidate the processes controlling macrophage seeding and development in the intestine and this was an aim of this thesis. In the adult healthy colon, two main mφ subsets can be identified: A dominant and homogenous one, made up of mature mφ, which express high levels of F4/80, MHC II, CX3CR1, are CD11bint/+, highly phagocytic and produce high amounts of IL10. The second mφ group is relatively smaller and is much more heterogeneous. These cells express intermediate levels of F4/80 and CX3CR1, are CD11b+ and can be divided into 3 subsets based on their levels of Ly6C and MHC II. These subsets represent a maturation continuum towards the mature mφ phenotype. Recent reports have suggested that resident macrophages in healthy tissues may be derived from yolk-sac and/or foetal liver precursors that seed tissues during development and subsequently self-renew locally. In contrast, it is proposed that macrophages in inflammation are generated by recruitment of blood monocytes, raising the possibility that these different origins could be exploited in therapy. However none of these studies have examined macrophages in the intestine and recent work in our laboratory has suggested that monocytes may be the precursors of macrophages in both healthy and inflamed gut of adult mice. Therefore, the aims of this thesis were to investigate the development of murine colonic mφ from birth until adulthood, examining the relative roles of the yolk sac, foetal liver and bone marrow monocytes, exploring their functions and comparing them with the well-characterised adult mφ. In addition, I also examined how mφ phenotype and functions are influenced by the microbiota using broad-spectrum antibiotics and germ free mice. Lastly, I examined the role of fractalkine and its receptor CX3CR1 in defining the development and functions of intestinal macrophages. Development of macrophages in early life The initial characterisation and comparison of colonic mφ subsets is included in Chapter 3. In this chapter, I describe a series of experiments adapting existing protocols and techniques used for examining the adult murine intestine in order to analyse the origin, phenotype and functions of murine colonic macrophages from late foetal life through to adulthood. These studies found that intestinal mφ are present before birth, with similar levels of phagocytic ability and IL10, TNFα and CD163 mRNA expression to the adult. However, the numbers and phenotype of mφ in the intestine do not reach the adult level until the 3rd week of postnatal life. This phenomenon appears to reflect the de novo recruitment of blood monocytes in a CCR2-dependent fashion at this time and throughout adult life, but not at early stages of life. In the colon of newborn mice, two macrophage populations can be observed and are clearly differentiated based on their F4/80 and CD11b expression: F4/80hi CD11bint/+ and F4/80lo CD11b+. Interestingly, unlike adult colonic F4/80hi mφ, the majority of F4/80hi neonatal cells do not express MHC II, however they gradually express this molecule as they age. In addition to acquiring MHC II expression, the two populations in the newborn colon gradually merge and from the 3rd week of life it is difficult to discriminate them reliably. My experiments show that both mφ subsets proliferate actively during the first 2 weeks of life, but this is later reduced and maintained at low levels indicating that there is no self-renewal of mature mφ. Moreover, fate-mapping analysis carried out in collaboration with Professor Frederic Geissmann, showed that yolk sac-derived precursors contribute only minimally to the pool of colonic mφ, even at early life stages. Conversely, additional fate mapping studies suggested that most intestinal macrophages are derived from Flt3+ progenitors. Taken together, the results in this chapter demonstrate that blood monocytes are vital in replenishing the intestinal macrophage pool in the steady state, setting them apart from other tissue macrophages, which derive from primitive progenitors. Investigating the effect of the microbiota on intestinal macrophage subsets In Chapter 4, I assessed the effects of the commensal microbiota on intestinal mφ, using two different approaches: First, I assessed the function and gene expression of colonic macrophages following administration of broad-spectrum antibiotics. My results showed that this did not alter the numbers, phenotype, intracellular cytokine production or mRNA expression by macrophages. Several reasons may account for this, including dose/nature of antibiotics, length of administration or lifespan of macrophages. To overcome these issues, I compared the phenotype of colonic mφ in germ free (GF) and conventionally (CNV) reared mice of different ages in collaboration with Dr David Artis. Absolute absence of microbiota in GF mice severely impacted Ly6Chi monocyte recruitment to the colon, suggesting that constant recruitment of monocytes to the gut is at least in part due to the microbial burden. The biggest differences between GF and CNV mice were evident at 3 weeks of age, when GF mice had a much lower number and frequency of monocyte-derived cells than their CNV counterparts. By 12 weeks of age, Ly6Chi mφ populations from GF mice were partially restored, although the expression of MHC II by F4/80hi mφ remained reduced. Additionally, I FACS-purified F4/80hi cells from GF and CNV adults and sent RNA for microarray analysis, the results of which we are waiting to receive. This data will provide further information regarding how GF intestinal mφ differ from those found in conventional animals. Role of the CX3CL1-CX3CR1 axis in mφ development and function As mature colonic mφ express high levels of the chemokine receptor CX3CR1 (fractalkine), finally, in Chapter 5 I went on to investigate the role of CX3CL1-CX3CR1 axis in colonic lamina propria. In addition to the high expression of CX3CR1 by colonic mφ, its ligand, CX3CL1 has been reported to be expressed at high levels by the intestinal epithelium. Furthermore, as there is strong evidence that the CX3CL1-CX3CR1 axis may be involved in inflammation in several tissues, we hypothesised this axis might play a role in mφ function in the gut. To this end, I examined mφ phenotype, activation status and survival following in vitro co-culture of WT or CX3CR1-deficient bone marrow-derived mφ with an epithelial cell line modified to express either the soluble or membrane-bound forms of CX3CL1. I also examined the development of chemically induced colitis in CX3CR1-deficient mice.
25
Pascal, Maud. "Innate Lymphoid Cells under Neuronal Control in the Small Intestine : vasoactive Intestinal Peptide potentiates ILC2 and ILC3 functions." Thesis, Sorbonne université, 2019. http://www.theses.fr/2019SORUS318.
Анотація:
L’intestin est une vaste surface de l’organisme constamment exposée aux substances ingérées et aux nombreux micro-organismes qui colonisent sa muqueuse. Afin d’assurer le maintien de son intégrité, plusieurs dispositifs de reconnaissance et de défense impliquent cellules immunitaires et neurones, faisant de lui un organe de choix pour l’étude des interactions neuroimmunes. La compréhension des éléments assurant un fonctionnement coordonné des Systèmes immunitaire (SI) et Nerveux (SN) dans l’intestin reste cependant partielle. Ce travail a porté sur l’étude des mécanismes régissant le fonctionnement intégré des SN et SI de l’intestin suite à une prise alimentaire. Nous démontrons que la libération de Peptide Intestinal Vasoactif (VIP) suite à une prise alimentaire impacte la fonction de cellules clés dans l’organisation de l’immunité intestinale, les cellules lymphoïde innées (ILC). Pour la première fois, on démontre qu’un neuropeptide modifie de manière anticipée la biologie des ILC2 et des ILC3 pour potentialiser l’effet de cytokines inductrices caractéristiques des immunités de type 2 ou de type 3, permettant une activation rapide et conséquente des ILC. Ce travail complexifie le réseau de régulation du fonctionnement des ILC et dévoile un nouveau rôle du VIP dans le maintien de l’homéostasie intestinale via sa capacité à anticiper et potentialiser les réponses immune de manière intégrée. La compréhension de ce nouveau mécanisme d’interactions neuroimmunes dans l’intestin ouvre la voie vers le développement de nouvelles stratégies thérapeutiques basées sur les propriétés du VIP pour prévenir et traiter des maladies infectieuses et inflammatoires de l’intestinThe intestine represents an extremely wide interface constantly exposed to substances that we ingest and to numerous micro-organisms that colonize its mucosae. Several mechanisms of recognition and defense involving both immune cells and neurons exist to ensure protection of the gut, setting the gut as a paradigm for neuroimmune interactions. However, how the nervous and immune systems coordinate and synchronize their action in the gut remain unclear. In this thesis, I aimed to elucidate the mechanisms underlying one type of neuroimmune communication occurring in the gut, during a physiological process: feeding. In this context, I demonstrated that the food-induced release of the Vasoactive Intestinal Peptide (VIP) impacts the function of the recently discovered “gatekeepers” of the gut immune system, Innate Lymphoid Cells (ILCs). For the first time, I showed that a neuropeptide induces an anticipatory priming of both ILC2 and ILC3, which could potentiate the effect of the canonical type 2 and type 3 inducer cytokines to lead a rapid and strong activation of ILCs. This work provides new insights in the highly complex regulatory network of ILCs and uncovers a new role for VIP in maintaining gut homeostasis through its ability to prime and eventually boost immune responses in an integrated and context dependent manner. The understanding of the neuroimmune interplay involving VIP in the small intestine opens the path toward the development of new therapeutic strategies based on VIP properties to treat infectious and inflammatory diseases of the gastrointestinal tract
26
Soualhi, Salima. "Rôles de SOX9 dans l’auto-renouvellement et la différenciation de l’épithélium intestinal." Thesis, Montpellier 1, 2014. http://www.theses.fr/2014MON13519.
Анотація:
Sox9 est un facteur de transcription exprimé au cours du développement de l'intestin et son expression est maintenue à l'âge adulte dans trois populations cellulaires : les cellules souches, les cellules de Paneth, et les cellules tuft. L'inactivation de Sox9 dans l'épithélium intestinal embryonnaire entraîne, chez l'adulte, une hyperplasie des cryptes ainsi que l'absence de cellules de Paneth. Ce projet de thèse vise à déterminer le rôle de Sox9 dans les cellules de Paneth (dont la fonction est altérée chez les patients atteints de la maladie de Crohn), à identifier les mécanismes par lesquels Sox9 régule la prolifération et à proposer des cibles de Sox9 dans les cellules tuft. À l'aide de modèles murins d'inactivation de Sox9 au niveau de l'épithélium intestinal adulte, nous avons montré que la perte de ce facteur conduit à une augmentation de la prolifération dans les cryptes, confirmant ainsi que Sox9 régule négativement ce processus. Nos résultats indiquent que Sox9 est essentiel au maintien de l'identité des cellules de Paneth et nous proposons qu'il assure cette fonction en réprimant des gènes requis pour la différenciation des cellules de Goblet : Muc2 et Klf4. La perte de Sox9 dans les cellules de Paneth s'accompagne d'une réduction importante des molécules antimicrobiennes, ce qui entraîne une dysbiose intestinale. Dans un environnement spécifique (en présence du « mouse norovirus »), les souris déficientes en Sox9 présentent une perméabilité intestinale augmentée et une susceptibilité à l'inflammation accrue. Les dysfonctionnements des réponses antimicrobiennes et immunitaires dans notre modèle sont comparables à ceux observés chez les patients atteints de la maladie de Crohn, suggérant une implication potentielle de Sox9 dans cette pathologie. De plus, ces altérations pourraient expliquer l'augmentation de l'apparition des tumeurs observée chez les souris dont l'épithélium intestinal est déficient en Sox9, dans le contexte d'une mutation du gène suppresseur de tumeur Apc. Enfin, nous avons identifié des gènes potentiellement régulés par Sox9 qui pourraient expliquer son rôle dans le contrôle de la prolifération. Ces découvertes seront importantes pour mieux comprendre le processus du renouvellement de l'épithélium intestinal et identifier précisément le rôle de Sox9 dans le maintien de l'homéostasie et au cours du processus de la tumorigenèse intestinaleSox9 is a transcription factor expressed during the intestinal development and its expression is maintained throughout adult age in at least three populations of cells: stem cells, Paneth cells and tuft cells. Sox9 inactivation in the embryonic intestinal epithelium leads to crypts hyperplasia and to the loss of the Paneth cell lineage. The aim of this project is to determine Sox9 function in the adult intestinal epithelium, especially its role in Paneth cells (which function is altered in patients affected by inflammatory diseases such as Crohn disease), to identify how Sox9 controls proliferation and to propose molecular targets of Sox9 in tuft cells. Using mice models to inactivate Sox9 in adult intestinal epithelium, we could show that Sox9 is required to limit proliferation in the crypts, thus validating the hypothesis that Sox9 regulates negatively proliferation. Our results indicate that Sox9 is essential to maintain Paneth cells identity and we proposed that it ensures this function by repressing genes specific for Goblet cells differentiation: Muc2 and Klf4. Loss of Sox9 in Paneth cells is associated with a reduction of antimicrobial molecules which causes intestinal dysbiosis. In a specific environment (in presence of the « mouse norovirus »), Sox9-deficient mice have a defective intestinal permeability and are more susceptible to inflammation. The dysfunctions of the mucosal defences and of immunity responses in our model resemble those observed in Crohn patients, thus suggesting a potential implication of Sox9 in this pathology. In addition, these alterations could be responsible for the increased susceptibility of our deficient model to develop tumors in the context of a mutation of the tumor suppressor gene Apc. We started to unravel potential molecular targets of Sox9 that are involved in the control of proliferation, that will be important to better understand Sox9 function in the intestinal epithelium self-renewal and to identify precisely Sox9 function to maintain homeostasis and during intestinal tumorigenesis
27
Ferron, Pierre-Jean. "Nouvelles approches in vitro pour l'étude des phycotoxines lipophiles seules ou combinées." Thesis, Rennes 1, 2015. http://www.theses.fr/2015REN1S023.
Анотація:
Certaines espèces de phytoplanctons produisent des métabolites secondaires hautement toxiques appelés phycotoxines. Ces phycotoxines peuvent contaminer les fruits et mer et poser un risque sanitaire pour l'homme. Elles sont responsables d'effets néfastes chez l'homme et peuvent provoquer des diarrhées, des nausées et des douleurs abdominales. Pour améliorer l'évaluation du risque sanitaire lié à la présence de phycotoxines dans les coquillages, une meilleure caractérisation du potentiel toxique est indispensable. Aussi, l'objectif de ce doctorat a été d'étudier les effets cytotoxiques des phycotoxines lipophiles seules et en mélange à l'aide de nouvelles approches in vitro en toxicologie. Nos études ont montrées que si les analogues de l'acide okadaïque (AO) induisaient tous l'apoptose, la génotoxicité, l'inflammation cellulaire et la perturbation du cycle cellulaire, sur les lignées intestinales Caco-2 et HT29-MTX, ces effets se produisaient à des concentrations différentes en fonction des toxines. Ensuite, nos recherches sur la lignée hépatique humaine HepaRG ont montrées l'implication des enzymes de phase I dans le processus de détoxication de l'AO et de ses analogues les dinophysistoxines (DTX), et de la pectenotoxin-2 (PTX-2). Pour finir, l'utilisation de la méthode des index de combinaison pour l'étude de la toxicité des mélanges binaires de toxines sur des lignées intestinales a mis en évidence des effets synergiques du mélange Azaspiracide-1/ YessotoxineSome species of phytoplankton produce highly toxic secondary metabolites called phycotoxins. Phycotoxins can contaminate seafood and pose a health risk to humans. They can cause several adverse effects in humans, including diarrhea, nausea and abdominal pain. To improve risk assessment associated with the presence of lipophilic phycotoxins in shellfish, a better characterization of the toxic potential is essential. The aim of this PhD was to study the cytotoxic effects of single and mixed lipophilic shellfish toxins using new approaches in in vitro toxicology. Our studies have shown that, analogs of okadaic acid (OA) induced apoptosis, genotoxicity, cellular inflammation and disturbance of the cell cycle, on intestinal cell lines Caco-2 and HT29-MTX, and that this effects occurred at different concentrations depending on the toxin. Then, our researches on human hepatic lineage HepaRG have shown the involvement of phase I enzymes in the detoxification of the pectenotoxin-2 (PTX-2), and OA and its analogues the dinophysistoxins (DTX). Finally, the use of the combination index method for studying the toxicity of binary mixtures of phycotoxins on intestinal cell lines showed synergistic effects of azaspiracid-1 / yessotoxin mixture
28
Postal, Bárbara Graziela. "Role of environmental factors on intestinal barrier dysfunctions reported in obesity." Thesis, Sorbonne université, 2019. https://accesdistant.sorbonne-universite.fr/login?url=http://theses-intra.upmc.fr/modules/resources/download/theses/2019SORUS310.pdf.
Анотація:
L’obésité est associée à une inflammation intestinale. Une altération de la barrière intestinale par des facteurs environnementaux et nutritionnels, pourrait être impliquée dans l’initiation ou la modulation de cette inflammation. Dans ce contexte, j’ai étudié le rôle d’un lipide alimentaire et du facteur de transcription Aryl Hydrocarbon (AhR). J’ai montré qu’un apport à court-terme d’huile de palme provoque dans l’intestin une altération de la barrière et une inflammation modérée chez la souris. Dans la lignée Caco-2/TC7, l’acide palmitique augmente la perméabilité intestinale, la sécrétion de la cytokine IL-8 via des mécanismes impliquant la synthèse des céramides. L’évaluation du rôle d’AhR sur l’inflammation intestinale de patients obèses a montré qu’elle est négativement corrélée avec le taux d’ARNm d’AhR et de ses gènes cibles. L'activation d’AhR empêche l'altération des jonctions cellule-cellule induite par l'huile de palme chez la souris; limite les altérations de la barrière et la sécrétion de cytokines pro-inflammatoires via l’implication de protéines kinases dans les cellules Caco-2/TC7. Ainsi la détérioration de l’intégrité de la barrière intestinale contribue à l’inflammation dans l’épithélium intestinal. Un effet protecteur contre les atteintes intestinales dans l’obésité pourrait être obtenus par l’activation d’AhR qui deviendrait ainsi une cible thérapeutiqueObesity is associated with low-grade intestinal inflammation. The intestinal barrier disruption by nutrients and environmental factors may be implicated on the onset or modulation of this inflammation. Then, my aim was investigating the role of diet lipid and the transcription factor sensitive to environmental changes, Aryl Hydrocarbon receptor (AhR) on intestinal dysfunctions in obesity. I showed that a short-term intake of palm oil altered the intestinal barrier and a moderated the intestinal inflammation in mice. In Caco-2/TC7 cells, palmitic acid increased the paracellular permeability and IL-8 expression and secretion via the ceramides synthesis pathway. The evaluation of the role of AhR on the intestinal inflammation of obese patients has shown that it is negatively correlated with the level of AhR mRNA and its target genes. AhR activation prevents the alteration of cell-cell junctions induced by palm oil in mice; limits the alterations of the barrier and the secretion of pro-inflammatory cytokines via the involvement of protein kinases in Caco-2/TC7 cells. Thus, these data demonstrated that alteration of the intestinal epithelial barrier integrity is an important contributor of gut inflammation. A protective effect against intestinal inflammatory responses and barrier function damage in obesity could be achieved by AhR activation, which would become a therapeutic target
29
Dabareiner, Robin Marie. "Evaluation of the microcirculation of the equine small intestine following intramural distention and reperfusion." Thesis, This resource online, 1992. http://scholar.lib.vt.edu/theses/available/etd-09052009-040410/.
30
Falcão, Slavador de Noronha de Alarcão. "Íleo pós-cirúrgico equino e o seu tratamento." Bachelor's thesis, Universidade Técnica de Lisboa. Faculdade de Medicina Veterinária, 2008. http://hdl.handle.net/10400.5/890.
Анотація:
Dissertação de Mestrado Integrado em Medicina VeterináriaCom este estudo pretendeu-se fazer uma revisão acerca das causas e do que se sabe da fisiopatologia do íleo pós-cirúrgico equino e as suas possíveis opções de tratamento. Este estudo foi baseado na revisão bibliográfica de artigos científicos e completada com um caso clínico observado durante o estágio na universidade de Gent. O objectivo deste trabalho foi fazer uma revisão da anatomia e fisiologia do tracto gastrointestinal equino. O principal objectivo é fornecer ao clínico de equinos uma ideia dos principais problemas associados com a cirurgia do tracto gastrointestinal, especialmente quando há compromisso do intestino delgado. Com base neste estudo, supõe-se que o ileo resulta de um conjunto de circunstâncias que promovem a hipomotilidade intestinal, entre as quais se encontram a inflamação intestinal, alterações do sistema nervoso entérico, alterações electrolíticas, endotoxémia e isquémia. Vários estudos sublinham que os agentes procinéticos são uma ferramenta muito importante no tratamento do íleo pós-cirúrgico em cavalos. Diferentes classes de fármacos procinéticos são usados, dependendo se o problema se localiza no intestino delgado ou no intestino grosso. Se o problema se localiza no intestino delgado, pode-se usar fármacos como a lidocaína, a metoclopramida e a eritromicina. Se o problema se localiza no intestino grosso podem-se usar fármacos como a naloxona, a neostigmina, a eritromicina e a lidocaína.
ABSTRACT The aim of this study was to review the causes and what is known about the pathophysiology of equine post-operative ileus and possible treatment options. This study was based on a review of scientific papers on the subject, completed with a case study observed during the practical training in Ghent University. The objective of this study was also to review the anatomy and physiology of the equine gastrointestinal tract. The overall goal was to provide to the equine clinician an idea of the principal problems associated with gastrointestinal surgery, especially when there is compromise of the small intestine. Based on this study, ileus may result from a variety of circumstances which promote intestinal hypomotility, amongst which the most important are intestinal inflammation, enteric nervous system inbalance, electrolytic inbalance, endotoxémia and isquemia. Several studies underline that prokinetic drugs are an important tool in the treatment of post-operative ileus in horses. Different classes of prokinetic drugs are used, depending on where the hypomotility is localized: small intestine or hindgut. If the problem is localized in the small intestine, we can use drugs like lidocaine, metoclopramide and erythromycin. If the problem is localized in the hindgut, we can use naloxone, neostigmine, erythromycine and lidocaine.
31
Franzo, Vanessa Sobue. "Considerações morfofisiológicas do intestino e do fígado de poedeiras comerciais submetidas aos diferentes programas de muda forçada /." Jaboticabal : [s.n.], 2006. http://hdl.handle.net/11449/104652.
Анотація:
Orientadora: Silvana Martinez Baraldi ArtoniBanca: Laura Satiko Okada Nakaghi
Banca: Daniela Oliveira
Banca: Selma de Fátima Grossi
Banca: Maria Rita Pacheco
Resumo: A muda forçada em poedeiras comerciais tem sido utilizada visando melhorar o desempenho zootécnico das aves por mais um ciclo de produção de ovos. Utilizou-se 32 galinhas poedeiras Hisex Brown com 58 semanas de idade submetidas a diferentes programas de muda forçada para análise do peso e comprimento das diferentes porções intestinais (duodeno, jejuno, íleo, ceco e cólon-reto), com o auxílio de uma balança de precisão e uma fita métrica, respectivamente. As aves foram alojadas em um galpão de postura com gaiolas (2 aves/gaiola) na Unesp, campus de Jaboticabal e expostas à 17 horas de luz diariamente com água e ração à vontade. O delineamento experimental foi inteiramente casualizado com 4 programas contendo 4 aves e 2 coletas aos 28 e 140 dias. Os programas utilizados foram: método Califórnia, baixo nível de cálcio, alto nível de zinco e baixo nível de sódio. Os dados foram submetidos à análise de variância e em caso de diferença significativa, as médias foram comparadas pelo teste de Tukey. Observou-se que aves submetidas ao método Califórnia por 10 dias tiveram respostas biométricas semelhantes aos animais que tiveram alto nível de zinco adicionado à dieta com menor peso corporal e de vísceras, além de menores comprimentos do intestino, além disso, aos 140 dias houve um aumento do peso corpóreo e, também do peso e do comprimento do intestino.
Abstract: The forced molting in commercial laying hens had being utilized for get better the performance of birds for one more cycle of production of eggs. In this study were used 32 Hisex Brown laying hen with 58 weeks of age submitted to different programs of forced molting. This experiment aimed the weight and length of the intestine (duodenum, jejunum, ileum, cecum and rectum). For the weight measurement was utilized one precision scale and for the length was used a measuring tape. The animals were caged in galvanized cage in aviary of Unesp, campus Jaboticabal and submitted of a program of growing light up to 17 hours a day after the induction period and the birds received water and ration ad libitum. The birds were distributed in a randomized experimental assay with 4 programs containing 4 birds and 2 production cycles (28 and 140 days). The animals were distributed into four programs: Califórnia method (control program), diet with low level of calcium, diet with high level of zinc and diet with low level of sodium. The data were submitted to the variance analysis and in case of significant difference, the averages were compared by the test of Tukey. It was observed that birds submitted to the California program were biometric responses similar to the animals that had high level of zinc added to the diet with smaller corporal weight and of visceras. It was observed that smaller lengths of the intestine and increase of corporal weight to the 140 days and increase of the weight and of the length of the intestine, too.
Doutor
32
Cong, Diem Huyen Ton Nu Quy. "Intestinal absorption and availability, a vascular perfusion study of the rat small intestine with benzoic acid." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape4/PQDD_0016/MQ54173.pdf.
33
Zangerle, Murray Tamsin Florencia Pamela. "Development of dendritic cells in the intestine." Thesis, University of Glasgow, 2016. http://theses.gla.ac.uk/7570/.
Анотація:
The intestinal tract is exposed to a large variety of antigens such as food proteins, commensal bacteria and pathogens and contains one of the largest arms of the immune system. The intestinal immune system has to discriminate between harmless and harmful antigens, inducing tolerance to harmless antigens and active immunity towards pathogens and other harmful materials. Dendritic cells (DC) in the mucosal lamina propria (LP) are central to this process, as they sample bacteria from the local environment and constitutively migrate to the draining mesenteric lymph nodes (MLN), where they present antigen to naïve T cells in order to direct an appropriate immune response. Despite their crucial role, understanding the function and phenotype of LP DC has been hampered by the fact that they share phenotypic markers with macrophages (mφ), which are the dominant population of mononuclear phagocyte (MP) in the LP. Recent work in our own and other laboratories has established gating strategies and phenotyping panels that allow precise discrimination between intestinal DC and mφ using the mφ specific markers CD64 and F4/80. In this way four bona fide DC subsets with distinct functions have been identified in adult LP based on their expression of CD11b and CD103 and a major aim of my project was to understand how these subsets might develop in the neonatal intestine. At the beginning of my PhD, the laboratory had used these new methods to show that signal regulatory protein α (SIRPα), an inhibitory receptor expressed by myeloid cells, was expressed by mφ and most DC in the intestine, except for those expressing CD103 alone. In addition, mice carrying a non-signalling mutation in SIRPα (SIRPα mt) had a selective reduction in CD103+CD11b+ DC, a subset which is unique to the intestinal LP. This was the basis for the initial experiments of my project, described in Chapter 3, where I investigated if the phenotype in SIRPα mt mice was intrinsic to haematopoietic cells or not. To explore this, I generated bone marrow (BM) chimeric mice by reconstituting irradiated WT mice with SIRPα mt BM, or SIRPα mt animals with WT BM. These experiments suggested that the defect in CD103+CD11b+ DC was not replicated in DC derived from BM of SIRPα origin. However as this seemed inconsistent with other data, I considered the possibility that 18 the phenotype may have been lost with age, as the BM chimeric mice were considerably older than those used in the original studies of SIRPα function. However a comparison of DC subsets in the intestine of WT and SIRPα mt mice as they aged provided no conclusive evidence to support this idea. As these experiments did show age-dependent effects on DC subsets, in Chapter 4, I went on to investigate how the DC populations appeared in the intestine and other tissues in the neonatal period. These experiments showed there were few CD103+CD11b+ DC present in the LP and migratory DC compartment of the MLN in the neonate and that as this population gradually increased in proportion with age, there was a reciprocal decrease in the relative proportion of CD103-CD11b+ DC. Interestingly, most of the changes in DC numbers in the intestine were found during the second or third week of life when the weaning process began. To validate my findings that there were few CD103+CD11b+ DC in the neonate and that this was not merely an absence of CD103 upregulation, I examined the expression of CD101 and Trem-1, markers that other work in the laboratory had suggested were specific to the CD103+CD11b+ DC lineage. My work showed that CD101 and Trem-1 were co- expressed by most CD103+CD11b+ DC in small intestine (SI) LP, as well as a small subset of CD103-CD11b+ DC in this tissue. Interestingly, Trem-1 was highly specific to the SI LP and migratory DC in the MLN, but absent from the colon and other tissues. CD101 expression was also only found on CD11b+ DC, but showed a less restricted pattern of distribution, being found in several tissues as well as the SI LP. The relative timing of their development suggested there might be a relationship between CD103+CD11b+ and CD103-CD11b+ DC and this was supported by microarray analysis. I hypothesised that the CD103-CD11b+ DC that co-expressed CD101 and Trem-1 may be the cells that developed into CD103+CD11b+ DC. To investigate this I analysed how CD101 and Trem-1 expression changed with age amongst the DC subsets in SI LP, colonic LP (CLP) and MLN. The proportion of CD101+Trem-1+ cells increased amongst CD103+CD11b+ DC in the SI LP and MLN with age, while amongst CD103+CD11b+ DC in the CLP this decreased. This was not the same in CD103-CD11b+ DC, where CD101 and Trem-1 expression was more varied with age in all tissues. CD101 and Trem-1 were not expressed to any great extent on CD103+CD11b- or CD103-CD11b- DC. The phenotypic development of the 19 intestinal DC subsets was paralleled by the gradual upregulation of CD103 expression, while the production of retinoic acid (RA), as assessed by the AldefluorTM assay, was low early in life and did not attain adult levels until after weaning. Thus DC in the neonatal intestine take some time to acquire the adult pattern of phenotypic subsets and are functionally immature compared with their adult counterparts. In Chapter 5, I used CD101 and Trem-1 to explore the ontogeny of intestinal DC subsets in CCR2-/- and SIRPα mt mice, both of which have selective defects in one particular group of DC. The selective defect seen amongst CD103+CD11b+ DC in adult SIRPα mt mice was more profound in mice at D7 and D14 of age, indicating that it may be intrinsic to this population and not highly dependent on environmental factors that change after birth. The expression of CD101 and Trem-1 by both CD103+CD11b+ and CD103-CD11b+ DC was reduced in SIRPα mt mice, again indicating that this entire lineage was affected by the lack of SIRPα signalling. However there was also a generalised defect in the numbers of all DC subsets in many tissues from early in life, suggesting there was compromised development, recruitment or survival of DC in the absence of SIRPα signalling. In contrast to the findings in SIRPα mt mice, more CD103+CD11b+ DC co-expressed CD101 and Trem-1 in CCR2-/- mice, while there were no differences in the expression of these molecules amongst CD103-CD11b+ DC. This may suggest that CCR2+ CD103-CD11b+ DC are not the cells that express CD101 and Trem-1 that are predicted to be the direct precursors of CD103+CD11b+ DC. I also examined the expression of DC growth factor receptors on DC subsets from mice of different ages, but no clear age or subset- related patterns of the expression of mRNA for Csf2ra, Irf4, Tgfbr1 and Rara could be observed. Next, I investigated whether Trem-1 played any role in DC development. Preliminary experiments in Trem-1-/- mice show no differences between any of the DC subsets, nor were there any selective effects on individual subsets when DC development from Trem-1-/- KO and WT BM was compared in competitive chimeras. However these experiments were difficult to interpret due to viability problems and because I found an unexpected defect in the ability of Trem-1-/- BM to generate all DC, irrespective of whether they expressed Trem-1 or not. 20 The final experiments I carried out were to examine the role of the microbiota in driving the differentiation of intestinal DC subsets, based on the hypothesis that this could be one of the environmental factors that might influence events in the developing intestine. To this end I performed experiments in both antibiotic treated and germ free adult mice, both of which showed no significant phenotypic differences amongst any of the DC subsets. However the study of germ free mice was compromised by recent contamination of the colony and may not be the conclusive answer. Together the data in this thesis have shown that the population of CD103+CD11b+ DC, which is unique to the intestine, is not present at birth. These cells gradually increase in frequency over time and as this occurs there is a reciprocal decrease in the frequency of CD103-CD11b+ DC. Along with other results, this leads to the idea that there may be a linear developmental pathway from CD103-CD11b+ DC to CD103+CD11b+ DC that is driven by non-microbial factors that are located preferentially in the small intestine. My project indicates that markers such as CD101 and Trem-1 may assist the dissection of this process and highlights the importance of the neonatal period for these events.
34
Lubin, Alexandre. "Preservation of the small intestine for transplantation." Thesis, McGill University, 1995. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=23915.
Анотація:
Transplantation of the small intestine is technically feasible, and the only potentially curative method for patients with short gut syndrome. However this procedure is still infrequent, partially because there is still no reliable method to preserve the small bowel (SB) for a reasonable period of time between removal from the donor and transplantation. In search of a suitable medium for SB preservation, we evaluated different solutions which have been successfully used for preservation of other human organs (Eurocollins (EC), University of Wisconsin (UW) and lactated Ringer's (LR)) and tried to improve their effectiveness by adding superoxide dismutase and catalase or verapamil. The adequacy of preservation was assessed by evaluating the physiological properties of the intestine in vitro, using either the rat syngeneic model of intestinal transplantation, or human intestine obtained from organ donors.LR is a simple, inexpensive and universally available solution, and when supplemented with verapamil, it was as effective as the more complex EC and UW as a protectant against ischemic damage during cold storage of rat ileum. Studies on human intestine validated the rat as an experimental model since the relative effectiveness of the different solutions was similar, however, the human bowel appeared more vulnerable to ischemic and mechanical damage. The results indicate that creation of an effective preservation solution for the small intestine should be possible through appropriate modification of currently available preparations.
35
Bain, Calum Cunningham. "Resident and inflammatory macrophages in the intestine." Thesis, University of Glasgow, 2012. http://theses.gla.ac.uk/3441/.
Анотація:
The healthy intestinal mucosa is home to the largest population of macrophages in body. Like all tissue macrophages, intestinal macrophages play vital roles in maintaining tissue homeostasis by removing apoptotic cells and any other cellular debris. In addition they maintain the integrity of the epithelial barrier and support the differentiation and maintenance of regulatory T cells in the mucosa. By virtue of their high phagocytic and bactericidal activity, these macrophages are also vital members of the innate immune system and are strategically positioned adjacent to the epithelium so that they can capture and eliminate any invading organism(s). However unlike other tissue macrophages, those found in the normal gut have several functional adaptations, such as hyporesponsiveness to toll-like receptor (TLR) ligands, which allow them to function without provoking overt inflammation. Macrophages are also abundant during intestinal inflammation, where they show increased TLR responsiveness, pro- inflammatory cytokine and chemokine production and enhanced phagocytic ability. Under these conditions, macrophages perpetuate inflammation. It remains unclear whether these distinct roles in healthy and inflamed intestine roles are carried out by discrete populations of macrophages, or if the resident macrophages alter their behaviour and become pro-inflammatory. One of the main obstacles to gaining a better understanding of the immunobiology of intestinal macrophages during steady state and inflammatory conditions is discriminating them from other mononuclear phagocytes (MP) in the mucosa, such as dendritic cells (DC). At the time of starting my project, it was becoming clear that markers such as F4/80 and CD11c were insufficient for distinguishing between macrophages and DC when used in isolation. Therefore, the aims of this thesis were to first establish reliable multi-parameter flow cytometry staining protocols to allow precise phenotypic and functional characterisation of macrophages in the healthy and inflamed mouse colon, and secondly, to explore the origins of these macrophage populations to assess whether they were derived from distinct precursors, or whether a relationship existed between them. Lastly, I examined the potential mechanisms underlying the characteristic TLR hyporesponsiveness that intestinal macrophages exhibit, focusing on the role of the inhibitory CD200R1-CD200 axis. In Chapter 3, I first set out to characterise phenotypically the macrophage populations present in the steady state mouse colon using multi-parameter flow cytometry. These studies revealed that expression of the chemokine receptor CX3CR1 could be used to identify two main populations of myeloid cells, the bigger of which was a homogeneous population of CX3CR1highCD11b+ macrophages that dominated the resting mucosa. A smaller population of CD11b+ cells expressing intermediate levels of CX3CR1 (CX3CR1int) was also present in the steady state mucosa, but this was remarkably heterogeneous, with at least 4 subsets distinguishable on the basis of Ly6C, class II MHC, F4/80 and CD11c expression. These included F4/80+Ly6ChighMHCIIneg CD11cneg cells that were phenotypically indistinguishable from blood monocytes, F4/80+Ly6C+MHCII+CD11c+/neg cells and F4/80+Ly6CnegMHCII+CD11c+/int cells that were phenotypically and morphologically similar to CX3CR1high macrophages except for their lower level of CX3CR1. Finally there was a minor subset of F4/80negLy6Cneg MHCII+CD11chigh cells that expanded markedly in response to in vivo flt3L treatment and appeared to be genuine DC. CX3CR1neg cells were also found within the CD11b+ population in the healthy mucosa, most of which were Siglec F+ eosinophils, together with a few neutrophils. In the second half of Chapter 3, I examined how these populations changed during acute colitis induced by feeding dextran sodium sulphate (DSS). These experiments demonstrated that the CX3CR1int compartment expanded dramatically during acute inflammation, with preferential accumulation of the Ly6Chigh subsets and relative loss of the CX3CR1high population as colitis progressed. Together these studies suggested that CX3CR1high and CX3CR1int cells represent resident and pro-inflammatory macrophages respectively. I next set out to explore the in vivo origin of the CX3CR1int and CX3CR1high populations, to address whether they were derived from independent precursors as would be predicted by current theories of monocyte heterogeneity, or if a relationship existed between them. By using adoptive transfer of purified BM monocytes, the studies described in Chapter 4 show that 'inflammatory' Ly6Chigh, but not Ly6Clow 'resident' monocytes replenished the CX3CR1high resident macrophage population in the steady state mucosa. This appeared to involve local differentiation of Ly6Chigh monocytes through CX3CR1int intermediary stages, which was accompanied by the acquisition of class II MHC, loss of Ly6C and upregulation of F4/80 and CX3CR1. In vivo BrdU incorporation studies supported the idea that the majority of CX3CR1int cells in the resting intestine represented short-lived intermediaries on their way to becoming CX3CR1high macrophages. Together these studies suggested that rather than representing independent macrophage subsets, the CX3CR1int and CX3CR1high cells in the resting colonic mucosa comprise a differentiation continuum from Ly6Chigh monocytes to mature CX3CR1high macrophages. Analysis of BM chimeric mice confirmed that BM-derived monocytes were the source of the vast majority of colonic LP macrophages. These findings were supported by the fact that CCR2 KO mice, in whom Ly6Chigh monocyte egress from the BM is blocked, lack Ly6Chigh colonic monocytes and have markedly reduced numbers of mature colonic macrophages. In Chapter 4, I also explored whether factors present in the normal mucosa, such as colony stimulating factor (CSF)-1, TGFbeta and the chemokine CX3CL1, could direct monocytes to acquire the phenotype of mucosal macrophages. Although initial in vitro studies suggest that none of these were effective on their own, in vivo administration of recombinant CSF-1 appeared to promote in situ monocyte differentiation in the gut. Taken together, the results in this chapter highlight that the CX3CR1high macrophage population is maintained by Ly6Chigh blood monocytes and that their differentiation is controlled by local factors in the mucosa. In Chapter 5, I went on to investigate whether the phenotypically identifiable differentiation of mucosal macrophages was accompanied by alterations in their functional capacity. Intracellular cytokine staining, qRT-PCR and reporter gene expression revealed that as Ly6Chigh monocytes differentiate locally through the CX3CR1int stages into CX3CR1high macrophages, they progressively acquired the ability to produce IL10 and have reduced production of pro-inflammatory mediators. In addition, the maturation of monocytes was accompanied by an increased ability to phagocytose and kill bacteria. Their response to exogenous stimulation by TLR ligands also altered as differentiation proceeded, with the Ly6Chigh monocytes responding robustly to TLR2 and TLR4 ligation in a TNF-alpha dominated manner, whereas the CX3CR1high macrophages responded less vigorously and their TNF-alpha production was balanced by IL10. This pattern was retained during experimental colitis, where the CX3CR1int cells showed enhanced spontaneous TNF-alpha production, whereas IL10 remained the dominant product of CX3CR1high macrophages. Adoptive transfer experiments in Chapter 6 then showed that donor Ly6Chigh monocytes were recruited to the mucosa of colitic mice, but unlike in resting mice, they failed to acquire the CX3CR1high phenotype.
36
Angus, Elizabeth Mary. "Studies of cell shedding in the intestine." Thesis, University of Liverpool, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.501717.
Анотація:
Intestinal epithelial gaps have only recently been returned to for further study, and most of this work has been carried out in mice. In the past identification of epithelial gaps in human intestinal mucosa has been questionable because of the limitations of conventional microscopy. In collaboration with Dr R. Kiesslich, using the newly available Pentax confocal endomicroscope to view the epithelium of the human gastrointestinal tract at the cellular level without fixation artefact, we have shown that epithelial gaps occur in both the small intestine and the rectum of healthy humans. These patients were undergoing a routine screening colonoscopy.
37
Serrano, Maria. "Immature intraepithelial lymphocytes in the small intestine." Thesis, University of Bristol, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.499939.
38
Alyami, A. M. "Pharmacology of benzodiazepines and GABA in intestine." Thesis, University of Bradford, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.384251.
39
Al-Sawan, Shorooq M. Z. "Phosphate absorption in the rat small intestine." Thesis, University of Newcastle Upon Tyne, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.287463.
40
Wallis, Jennifer Lesley. "Glucose transport in the aged small intestine." Thesis, University of Newcastle Upon Tyne, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.287145.
41
Fonseca, Monica Rosalia Jaime. "An engineering understanding of the small intestine." Thesis, University of Birmingham, 2012. http://etheses.bham.ac.uk//id/eprint/3522/.
Анотація:
The main objective of this research was to understand phenomena occurring during food digestion and nutrients absorption in the small intestine from an engineering perspective. Intestinal flow and mixing processes were simulated using a dynamic in vitro Small Intestine Model (SIM). Of particular interest was to study the effect that mixing and food formulation has on glucose absorption and starch hydrolysis. Results showed the effect of segmentation motion on nutrient delivery to the intestinal wall as a consequence of changes in the mass transfer coefficient. This is most likely due to the increased mixing in the SIM. Experiments of starch digestion with and without the presence of guar gum have shown that viscous fibres reduce the rate of starch digestion and glucose absorption by impairing mixing and reducing diffusion within the fluid. Similarly, use of particulate systems demonstrated a significant effect on the delivery rates. Flow visualization techniques used for studying flow paths in the SIM showed that this in vitro model reproduces the characteristic flow events and mixing found in the small intestine in vivo. This research provides insights into the role of mixing on enhancing mass transfer on the course of digestion-absorption processes and also the action of viscous polysaccharides on the delay of glucose absorption in the small intestine. The end findings resulted in a better understanding of the factors which control the development of new functional food that could be applied both in academia and industry.
42
Scott, Charlotte Louise. "Characterisation of dendritic cells in the intestine." Thesis, University of Glasgow, 2014. http://theses.gla.ac.uk/4829/.
Анотація:
Due to the large surface area of the gut and its continual exposure to a wide variety of agents including dietary constituents, commensal bacteria and pathogens, the intestinal arm of the immune system has evolved to be the largest component of the immune system. It must be able to discriminate between harmless and harmful antigens, so that it can induce tolerance to harmless commensal, self or dietary antigens, but active immunity against pathogens. As the sentinels of the immune system, intestinal dendritic cells (DCs) are central to these processes, continually sampling antigen in the environment and migrating to the mesenteric lymph nodes (MLNs), where they present the antigen to naïve T cells and induce appropriate T cell responses. However the nature and functions of DCs in the intestine remains a topic of debate. Their characterisation has been hampered by the use of non-specific and overlapping markers which has led to intestinal DCs being confused with other cells of the mononuclear phagocyte system, especially macrophages (mφs) which vastly outnumber DCs in the intestinal mucosa. While considerable progress has been made in recent years with the identification of CD103 and CX3CR1 as mutually exclusive markers of DCs and mφs respectively, it has become assumed that CD103+ DCs are intrinsically tolerogenic and thus it remains unclear how DCs contribute to active immunity in the intestine. Furthermore it is unknown whether CD103 is sufficient to define all intestinal DCs, or whether bona fide CD103- DCs may also exist. Thus a major aim of my project was to develop methods that allowed precise characterisation of the mononuclear phagocytes in the intestinal lamina propria (LP) and examine the functions of phenotypically defined subsets. As part of this, I also examined the contribution of the inhibitory signalling receptor, signal regulatory protein alpha (SIRPα) co-expressed by CD11b+ DCs, in regulating intestinal DC function. In Chapter 3, I set out to examine the phenotype of mononuclear phagocytes in the small intestine lamina propria (SI LP). Initially I confirmed previous studies that CD103 and CX3CR1 were mutually exclusive markers of DCs and mφs respectively. This identified 2 populations of DCs separated on the basis of CD11b expression, together with two populations of mφs distinguished by their levels of CX3CR1. However, further experiments examining F4/80 expression in combination with the recently identified mφ-specific marker CD64 showed that the CX3CR1int CD103- MPs were heterogeneous. Although the majority were F4/80+CD64+CD11b+ mφs, I could also identify two additional populations that were F4/80-CD64- and could be separated on the basis of CD11b expression. I hypothesised these were DCs and this was supported by the fact that all 4 subsets of putative DCs could also be found amongst CD11c+MHCIIhi migratory DCs in the MLNs and in pseudo-afferent intestinal lymph. All the subsets also expressed genes and markers of DCs but not mφ and were dependent on Flt3L in vivo. Unlike CD64+ mφs, the DC subsets had no ability to phagocytose E. coli particles. Four similar subsets were also identified in the colonic LP, however the proportions of the subsets in this location were distinct from those seen in the SI LP. While the CD103+CD11b+ DCs were the main subset in the SI LP, in the colonic LP the CD103+CD11b- DCs dominated. Having identified two novel populations of genuine CD103- DCs in the intestinal LP, in Chapter 4 I went on to examine their origin. Previous reports had shown that CD103+ LP DCs were derived from DC-committed precursors (pre-DCs), whereas CD103- MPs were reported to be of monocyte origin. However as I had shown the CD103- MPs to include both DCs and mφs, it was necessary to re-examine their origin using appropriate gating strategies. Adoptive transfer of pre-DCs from the BM into resting WT mice generated all subsets of DCs in the LP, including the two novel populations of CD103- DCs I had identified. In contrast adoptive transfer of Ly6Chi monocytes into monocytopenic CCR2-/- recipients generated mφs exclusively. By comparing the small intestine, colon and spleen, I could show that the development of pre-DCs was determined by the tissue they entered, as the progeny took on the same subset profiles as seen in the endogenous DC populations. Thus the differentiation of pre-DCs appears to be driven by the local microenvironment. By tracking the appearance of donor-derived DCs over time, I could monitor their differentiation in situ. These studies and experiments using BrdU incorporation showed that all DC subsets turned over much more rapidly in vivo than mφs and that a significant proportion were actively dividing in situ. No clear differences suggesting a precursor-product relationship between any of the DC subsets could be seen in these kinetic experiments. To gain a better idea of how the DC subsets might develop, I also examined them in neonatal animals and examined the effects of administering broad-spectrum antibiotics. These studies demonstrated that the CD103+CD11b+ DCs were likely regulated by the presence of specific microbiota as they did not develop in the neonatal animals until day 7 after birth and were increased in proportion following administration of antibiotics. In Chapter 5, I examined how the DC populations might behave during inflammation, using DSS colitis, post-operative ileus and infection with Citrobacter rodentium as models. DSS-colitis caused considerable inflammatory infiltrate and the number of DCs was increased, however there were no subset specific differences. Post-operative ileus also caused inflammation characterised by monocyte and neutrophil infiltration, but had few effects on the DC populations. Infection with C. rodentium resulted in a selective increase in the number of CD103- DCs in the colonic LP, suggesting these may be involved in modulating the Th17 response which characterises the protective immune response in this infection. By transferring pre-DCs into colitic mice, I found that these still gave rise to all the DC subsets during inflammation. In Chapter 6, I examined the functions of the phenotypically defined subsets of LP DCs by pulsing them with ovalbumin (OVA) protein in vitro and culturing them with OVA-specific CD4+ or CD8+ T cells. Consistent with their expression of CD8α and XCR1, I found the CD103+CD11b- DCs to be the most efficient at cross-presenting antigen to naïve CD8+ T cells and they were also the most efficient inducers of IFNγ-producing CD4+ T cells. All populations of DCs could induce FoxP3+ TReg cells, but consistent with their ability to produce retinoic acid as measured by the ALDEFLUOR assay, the CD103+ DC subsets were most efficient at this. The CD103+CD11b- subset also expressed the TGFβ-activating integrin αvβ8. In contrast, induction of IL17a-producing CD4+ T cells was a function of CD103+CD11b+ and CD103-CD11b+ DCs, with the latter being the most efficient. In Chapters 7 and 8, I examined the role of the inhibitory molecule SIRPα in intestinal DC behaviour by examining the DC populations in SIRPα mutant (mt) mice, which have a truncated cytoplasmic domain and hence cannot signal intracellularly. Despite being expressed by most myeloid cells including all CD11b+ DC subsets and CD64+ mφs, SIRPα mt mice had a selective defect in the number of CD103+CD11b+ DCs in the LP and MLN. This correlated with a reduction in the number of Th17 cells in the LP of steady state SIRPα mt mice and these mice showed reduced levels of Th17 cell induction after antigen-specific immunisation and infection by C. rodentium. In parallel, SIRPα mt mice had impaired clearance of C. rodentium infection. T cells from SIRPα mt mice did not have an intrinsic defect in their ability to be polarised to the Th17 phenotype and CD103+CD11b+ DCs from SIRPα mt LP were fully capable of priming Th17 cells in vitro.
43
Bodnar, G. B. "Aspects of diagnosing congenital large intestine pathology." Thesis, БДМУ, 2021. http://dspace.bsmu.edu.ua:8080/xmlui/handle/123456789/19094.
44
Ehteshami, Zahra. "Characterising the mechanical properties of large intestine." Thesis, University of Leeds, 2015. http://etheses.whiterose.ac.uk/12500/.
Анотація:
This research was carried out to characterise mechanical properties of the large intestine. Assessing the mechanical properties of tissue plays an important role in understanding the links between histological structure and physical properties, physical functioning and normal anatomy. The mechanical properties of large intestine are poorly understood but essential for more accurate characterisation of their behaviour, for example during interaction with surgical instrumentation or devices. This project was set in the context of designing a new robotic colonoscopy device. The aim of this study was to develop and evaluate a robust methodology to characterise the ex-vivo mechanical properties of porcine large intestine tissue and create a database of these properties. In order to study the unique and complex physical properties of the large intestine two common techniques were employed: indentation and tensile stretching. A series of indentation and tensile tests were conducted and the time, strain-rate and strain history dependent responses of porcine large intestine during loading and stress relaxation were observed. Linear and non-linear models were used to analyse the tissue response. The results identified strong dependency of the large intestine mechanical properties to strain-rate and loading history. Tissue preconditioning was also found to be an effective way to stabilise the tissue response in air. Tissue hydration was also found to better preserve the natural state of tissue similar to the in-vivo environment. One of the most important observations was the necessity to produce an appropriate testing protocol for such investigations. Guidelines are proposed to set the requirements for mechanical tissue characterisation. For in-vivo investigation of tissue properties, a system based on measuring acoustic impedance properties of the tissue was successfully designed. Stiffness and tissue relaxation properties of the large intestine were examined using this probe and the results were linked back to the indentation outcomes. This system has the capability to be miniaturised and deployed during conventional colonoscopy or robotic hydro-colonoscopy.
45
Jenkins, Julie Kay. "Gluconate metabolism in Lactobacillus and its role in persistence in the human intestine." Connect to resource, 2005. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1124142014.
Анотація:
Thesis (Ph. D.)--Ohio State University, 2005.Title from first page of PDF file. Document formatted into pages; contains xi, 102 p.; also includes graphics (some col.). Includes bibliographical references (p. 95-102). Available online via OhioLINK's ETD Center
46
Levy, Jonathan. "Étude du rôle de l’autophagie dans la cancérogenèse intestinale." Thesis, Paris 11, 2014. http://www.theses.fr/2014PA11T049/document.
Анотація:
Considéré comme un cancer de l'âge mûr, l'incidence du cancer colorectal ne cesse d'augmenter avec l'allongement de la vie. Dans la majorité des cas, le cancer colique est associé à une mutation du gène suppresseur de tumeur Apc, contrôlant l’activation de la signalisation Wnt/β-caténine. Afin, d'identifier de nouveaux acteurs de la tumorigenèse colique, notre laboratoire a développé des modèles murins de mutation du gène Apc qui ont pour avantage de mimer la pathologie humaine (Colnot et al, 2004 ; Andreu et al, 2005). La création de ces modèles a permis à l’équipe de démontrer i) qu’une activation physiologique de cette voie contrôle la prolifération des cellules souches et des progéniteurs ainsi que leur différenciation et ii) qu’une activation aigüe est suffisante pour déclencher l’initiation tumorale intestinale (Andreu et al, 2005; Andreu et al, 2008). Les travaux antérieurs à mon arrivée ont permis d’identifier différents évènements moléculaires et cellulaires induits en cascade suite à l’activation pathologique de la voie Wnt/β-caténine. Parmi ceux-ci, une induction transcriptionnelle de gènes impliqués dans l'autophagie a été mise en évidence. Ce processus d'auto-cannibalisme cellulaire est associé à de nombreuses pathologies telles que les maladies neurodégénératives ou infectieuses. Cependant, le rôle de l'autophagie dans le cancer reste ambivalent et son implication dans le cancer colique demeure inconnue.Dans ce contexte, mon travail de doctorat a consisté à répondre aux questions suivantes :L’induction transcriptionnelle de gène Atg s’accompagne-t-elle d’une activation du processus d’autophagie à tous les stades de la progression tumorale intestinale murine et humaine?Des études de transcriptomique à haut débit nous ont permis d’identifier une induction transcriptionnelle de gènes clés du processus d’autophagie tels qu’Atg7. Cependant, l’activation fonctionnelle de l’autophagie n’est pas toujours associée à une augmentation de la transcription des acteurs de ce processus. Nous nous sommes donc intéressés aux marqueurs couramment décris dans la littérature et permettant d’établir l’état d’activation du flux autophagique. Ainsi, nous avons étudié le niveau d’expression de ces marqueurs par des expériences de western-blot et d’immuno-marquages sur des échantillons tumoraux humains et murins à différents stades de la progression du CRC. L’inhibition de l’autophagie impacte-t-elle la carcinogénèse colorectale?Dans ce contexte, nous avons généré un modèle murin de délétion conditionnelle et simultanée d'un allèle du gène Apc et des deux allèles du gène Atg7 (gène clé de l'autophagie) spécifiquement dans les cellules épithéliales intestinales. Afin de suivre l'apparition et l'évolution des tumeurs au cours du temps, nous avons mis au point une nouvelle méthode non-invasive de reconstruction tridimensionnelle de côlons de souris, issue d'imagerie échographique à haute résolution. Dans le but de caractériser l’impact de l’inhibition de l’autophagie, les modifications propres à la cellule déficiente en autophagie ont été explorées, notamment le statut énergétique ainsi que les changements dans l’environnement immunitaire et microbien de l’épithélium intestinal. Finalement, l’inhibition génétique de l’autophagie dans notre modèle murin, prédisposé au développement de tumeurs intestinales, nous a permis de caractériser l’implication de l’autophagie dans la carcinogénèse colique, ainsi que les mécanismes moléculaires et cellulaires liant l’auto-cannibalisme cellulaire à la pathologie tumoraleColorectal cancer is one of the major causes of cancer-related deaths. We took advantage of Apc mutant mice that mimic the adenomatous polyps that affect humans with an inactivated Apc gene, to gain insight into the critical events that affect the development of colorectal cancer. We show that autophagy, a catabolic pathway involved in the degradation of intracellular proteins and organelles, is activated in intestinal murine and human cancer and its inhibition has a crucial role in controlling tumorigenesis. We report that the in vivo conditional deletion of the essential autophagy gene Atg7 in intestinal epithelial cells inhibits the formation of pre-cancerous lesions resulting from Apc loss by enhancing immunosurveillance. The antibody-mediated depletion of CD8+ T cells demonstrated a critical role for CD8+ T cells in antitumoral responses resulting from the inhibition of autophagy. We used a broad-spectrum antibiotics treatment to show that the expansion of IFN-producing CD8+ T cells following the deletion of Atg7 is dependent on the intestinal microbiota and is associated with Paneth and goblet cell defects. In addition, the inhibition of autophagy affected tumor cell growth and restrained cancer growth for extended time periods. We demonstrate that the inhibition of autophagy in Apc tumor cells results in a stress response accompanied by metabolic defects, characterized by AMPK activation and p53 cell cycle arrest. This study suggests that autophagy inhibitors may suppress tumorigenesis in patients at high risk of developing colorectal cancer
47
Rothe, Monique [Verfasser], and Michael [Akademischer Betreuer] Blaut. "Response of intestinal Escherichia coli to dietary factors in the mouse intestine / Monique Rothe. Betreuer: Michael Blaut." Potsdam : Universitätsbibliothek der Universität Potsdam, 2013. http://d-nb.info/1037027485/34.
48
Zhu, Yuanbo. "Intestinal epithelial cell-derived IL‐15 determines local maintenance and maturation of intraepithelial lymphocytes in the intestine." Kyoto University, 2020. http://hdl.handle.net/2433/253170.
49
Dostaler, Suzanne Marie-Louise. "Uptake of estrogen by rabbit liver and intestine." Thesis, University of Ottawa (Canada), 1986. http://hdl.handle.net/10393/4766.
50
Gagnon, Jeffrey. "The proprotein convertases in the murine small intestine." Thesis, University of Ottawa (Canada), 2008. http://hdl.handle.net/10393/28225.
Анотація:
The small intestine (SI) is a major endocrine organ with over 40 precursor hormones produced and proteolytically matured into active peptide hormones which signal throughout the body including the pancreas and CNS. One group of enzymes believed to be responsible for this maturation is the family of protein convertases (PCSKs). Using double immunofluorescent microscopy, the spatial localization of PCSK1, 2 and 3 in each region of the SI and colocalization with potential intestinal substrates was examined in mice. A unique regional expression pattern was observed for each of the PCSKs and several hormones examined exhibited high levels of colocalization. Next the gastrointestinal physiology of the PCSK2 knock out (KO) mouse was examined and correlated with the circulating levels of hormones known to mediate these functions. KO animals consume less food immediately after refeeding and have delayed intestinal transit. Several of the hormones responsible for feeding and intestinal motility were modulated in the PCSK KO animals. These studies suggest that the PCSK1 2 and 3 are present in the SI and required for normal functionality.