Orientadores: Maria de Lourdes Setsuko Ayrizono, Frederico Camelo Leão / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-25T05:27:18Z (GMT). No. of bitstreams: 1 Acciari_ArleteSilva_M.pdf: 1483280 bytes, checksum: 5d8937c9decda267b2ccf2c0f397a615 (MD5) Previous issue date: 2014 / Resumo: Introdução: A doença de Crohn é uma enfermidade crônica, com tratamento contínuo e prolongado. Além de sintomas físicos como dor abdominal, diarreia e emagrecimento, os pacientes são acometidos por crises de ansiedade, depressão e perda na qualidade de vida, necessitando de acompanhamento psicológico. Objetivo Geral: Avaliar os efeitos da Psicoterapia Breve Transpessoal em pacientes com doença de Crohn. Objetivos Específicos: Analisar os resultados da Psicoterapia Breve Transpessoal quanto à saúde geral, qualidade de vida, ansiedade, depressão e estados de desesperança e observar possíveis correlações entre as condições psicológicas e a atividade da doença de Crohn. Casuística e Métodos: A amostra foi composta por 11 pacientes com doença de Crohn, de ambos os sexos e com idade entre 25 anos e 55 anos. Utilizou-se o método clínico e o procedimento consistiu no atendimento em Psicoterapia Breve Transpessoal com referencial teórico da Abordagem Integrativa Transpessoal, com coleta de dados antes e depois da psicoterapia. Para a coleta de dados foram utilizados os seguintes instrumentos: Questionário Sociodemográfico, Índice de Atividade da Doença de Crohn, Inflammatory Bowel Disease Questionnaire, Questionário de Saúde Geral de Goldberg, Inventário de Ansiedade, Inventário de Depressão e Escala de Desesperança. Utilizou-se da análise descritiva e a metodologia estatística, com teste de Wilcoxon. Resultados: A intervenção mostrou-se eficaz para todos os instrumentos avaliados (p<0,05), com melhor resultado para redução da depressão (-76,8%), seguido da ansiedade (-62,0%) e redução no estado de desesperança (-61,2%); com melhora no estado de saúde geral (40,4%) e na qualidade de vida (35,3%). A atividade da doença avaliada pelo Índice de Atividade da Doença de Crohn apresentou redução de -38,1%. Conclusão: O processo psicoterapêutico trouxe significativos benefícios aos pacientes com doença de Crohn, com redução dos níveis de ansiedade, depressão, estado de desesperança; melhorou o estado de saúde geral e a qualidade de vida dos pacientes com DC. Houve uma melhora nas condições psicológicas dos pacientes com DC, demonstrando a correlação direta entre aspectos psicológicos e a atividade da doença / Abstract: Introduction: Crohn¿s disease is a chronic illness with continuous and longstanding treatment. In addition to physical symptoms such as abdominal pain, diarrhea and slimming, patients are affected by anxiety crises, depression and loss in life quality, requiring psychological assistance. General objective: Evaluating the effects of Transpersonal Brief Psychotherapy on patients with Crohn¿s disease. Specific Objectives: Analyzing the results of Transpersonal Brief Psychotherapy on general health, life quality, anxiety, depression and states of hopelessness and observing the possible correlations between psychological conditions and activity Crohn¿s disease. Casuistry and Methods: The sample was composed by 11 people sick with Crohn¿s disease of both sexes and aged from 25 to 55 years old. It was used the clinical method and the procedure consisted of treatment with TBP based on the theoretical reference of the Transpersonal Integrative Approach along with data collection before and after psychotherapy. The following instruments were used to data collection: Sociodemographic Questionnaire, Crohn¿s Disease Activity Index, Inflammatory Bowel Disease Questionnaire, General Health Questionnaire, Beck Anxiety Inventory, Beck Depression Inventory and Beck Hopelessness Scale. In order to evaluate the results it was used the descriptive analysis and the statistical methodology with Wilcoxon test. Results: The intervention turned out to be effective to all of the evaluated instruments (p<0.05), and the best result was to the decrease of depression (-76.8%), followed by anxiety (-62%) and reduction on the state of hopelessness (-61.2%); there was improvement on general health state (40.4%) and in life quality (35.3%). The disease activity, assessed by the Crohn¿s Disease Activity Index, has decreased by -38.1%. Conclusion: Conclusion: The psychotherapeutic process has brought meaningful benefits to patients with Crohn¿s disease, with decrease on anxiety levels, depression, state of hopelessness and reduction in the activity Crohn¿s disease, consequently, it has improved general health and quality of life of patients with CD. There was an improvement in the psychological status of patients with CD, demonstrating the direct correlation between psychological aspects and disease activity / Mestrado / Fisiopatologia Cirúrgica / Mestra em Ciências

Orientador: Mário Roberto Maróstica Júnior / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia de Alimentos / Made available in DSpace on 2018-08-21T23:59:26Z (GMT). No. of bitstreams: 1 Silva_JulianaKellyda_M.pdf: 1332113 bytes, checksum: e1dba8a206478de60e1e2656d6154548 (MD5) Previous issue date: 2013 / Resumo: O maracujá (Passiflora edulis) é uma variedade cultivada no Brasil, destinada principalmente à indústria de suco, mas seu processamento gera muitos resíduos. Estes subprodutos podem ser fontes de compostos bioativos, atuando na prevenção e tratamento do estresse oxidativo e agravos à saúde. Neste sentido, o escopo deste trabalho foi avaliar a ação antioxidante da farinha da casca de P. edulis (PPF) em ratos saudáveis e com colite induzida. Também foi avaliada a ação da PPF na microbiota cecal e na produção de ácidos graxos de cadeia curta (AGCC) dos animais saudáveis. A caracterização química mostrou que a PPF possui aproximadamente 48 % de fibra insolúvel e 17 % de fibra solúvel. O teor de fenóis totais na PPF foi 2,53±0,03 mg GAE g-1, de acordo com análise de Folin-Ciocateau. Nos ensaios biológicos foram utilizados ratos Wistar machos (77 dias de idade). Para o preparo da dieta experimental (Peel) 50% do teor de celulose da dieta padrão foram substituídos por fibra de PPF. No primeiro ensaio, os animais foram divididos em 2 grupos: Peel e Control (n=4). Após 15 dias os animais foram anestesiados e sacrificados. O grupo Peel apresentou maior ingestão diária de dieta, sem alteração ponderal, porém mostrou menores níveis de albumina sérica e proteína total em comparação ao grupo Controle. Não houve diferenças no potencial antioxidante sérico de acordo com ensaio de FRAP e TBARS, mas o grupo Peel demonstrou menor capacidade antioxidante comparado ao grupo Controle, de acordo com a análise de ORAC. Nos rins dos animais do grupo Peel houve diminuição na peroxidação lipídica e atividade da enzima Superóxido Dismutase (SOD) em comparação aos animais Controle. Porém, no fígado dos animais que consumiram PFF, houve maior nível de TBARS e atividade de Glutationa Redutase (GR), e redução da atividade de Glutationa Peroxidase (GPx). O teor de AGCC foi maior no conteúdo cecal do grupo Peel, sem alteração na microbiota ou pH fecal. Estes achados sugerem que a ingestão de PPF pode melhorar saúde intestinal ao promover aumento da produção AGCC, além de reduzir a peroxidação lipídica nos rins em ratos Wistar. Há ainda evidências que a PPF possa conter compostos termogênicos. No segundo ensaio biológico, os animais foram divididos em 4 grupos: Casca Colite, Casca Controle, AIN Colite e AIN Controle (n=6). Após uma semana de adaptação à dieta, foi realizada injeção retal de ácido 2,4,6-trinitrobenzenosulfônico (TNBS) para indução da colite nos animais; no grupo Controle, o procedimento foi realizado utilizando solução salina 0,9 m/v em substituição ao TNBS. Os animais tratados mostraram melhora no potencial antioxidante sérico, segundo os ensaios de TBARS e ORAC, bem como modulação das enzimas antioxidantes SOD (cérebro e fígado), GR e GPx (fígado) em relação aos grupos AIN. Porém, nos grupos Peel houve elevação da peroxidação lipídica no fígado. Apesar da casca de maracujá ser boa fonte de fibras e compostos fenólicos, sendo uma alternativa de ingrediente para indústria de alimentos com ação antioxidante, além de amenizar a geração de resíduos, é preciso investigar melhor seus efeitos a nível hepático. / Abstract: Passion fruit (Passiflora edulis) is a broadly cultivated variety in Brazil and mainly used in the juice industry. Passion fruit processing results in several residues which may represent 50% fruit's gross weight. Fruit byproducts, as the peels, oftentimes have greater amount of bioactive compounds, including antioxidant substances, which could act in the prevention or treatment of the oxidative stress and pathologies. The aim of this study was to evaluable antioxidant action of P. edulis peel flour (PPF) in healthy rats, beyond its effect in rats with induced colitis. The determination of PPF proximate composition showed 48 % of insoluble fiber and 17 % of fiber soluble. Total phenolic was 2.53 ± 0.03 mg GAE g-1 by Folin-Ciocateau assay. In the biological assays seventy seven-days-old male Wistar rats were used. The experimental diet was prepared with fifty percent of the cellulose content of standard diet replaced by fiber from PPF. In the first assay, the animals were divided in 2 groups: Peel and Control (n= 4). After 15 days of diet intake, the animals were naesthetized and sacrificed. PPF group consumed greater amount of diet without alterations in body weight of animals, but serum levels of total albumin and protein were lower than Control group. The animals that received PPF in the diet showed no differences in serum antioxidant status (FRAP and TBARS assays), but they presented lower antioxidant potential according to ORAC assay. Animals from Peel group showed a reduction in kidneys lipid peroxidation and SOD activity compared to the control group. In addition, the livers of the animals fed with PPF showed high TBARS levels, increased GR activity and decreased GPx activity. The SCFA in the cecal content were greater in Peel group, without alteration in microbiota or fecal pH. These findings suggest that the PPF intake could improve bowel health by increasing in SCFA production, further it reduced lipid peroxidation in kidneys. Some evidences show that P. edulis peel could contain thermogenic/ ergogenic compounds. In the second biological assay, the animals were divided in 4 groups: Peel Colitis, Peel Sham, AIN Colitis, AIN Sham (n= 6). After one week of adaptation, the colitis induction was performed by rectal injection of TNBS. The animals that received PPF showed improvements in serum antioxidant potential (ORAC and TBARS assays), as well as modulation of antioxidant enzymes activities in brain (SOD) and liver (SOD, GR and GPx) relative to AIN groups. On the other hand, hepatic lipid peroxidation in Peel groups was increased. P. edulis peel is a rich source of fiber and phenolic compounds and could be an alternative ingredient to food industry which might avoid the oxidant action and to reduce the residue production. However, more investigations are necessaries to investigate possible hepatic effects / Mestrado / Nutrição Experimental e Aplicada à Tecnologia de Alimentos / Mestra em Alimentos e Nutrição

English Abstract Crohn's disease together with ulcerative colitis, is a type of inflammatory bowel disease (IBD) with increasing incidence and prevalence in developed countries. IBD is an immunologically mediated multifactorial disease and it's mechanism of action is still unknown. Current well- established treatment targets the inflammation with corticosteroids and immunosuppressive drugs. Apart from the intestinal inflammation, which is the primary target of the treatment, patients are characteristically afflicted with intestinal dysbiosis. Therefore, possible interventions might be an adjuvant or biological therapy. Adjuvant therapy directly aims the microbiota with probiotics, whereas the target of biological therapy is TNF-α, a pro- inflammatory cytokine excessively secreted by macrophages. The aim of this thesis is to evaluate intestinal microbiota composition changes in IBD patients with regard to courses of adjuvant and biological therapy. Bacterial diversity was analyzed using three different DNA extraction techniques. Rapid beat beating + column (RBB+C) was chosen for analyzing patient samples, as it showed the highest DNA yield and the highest DNA purity. Primarily the bacterial diversity was analyzed using degradation gradient gel electrophoresis (DGGE) with subsequent sequencing of bands of...

A l`heure où le cancer a supplanté les maladies cardiovasculaires en tant que première cause de mortalité en France, le CCR représente la deuxième cause de mortalité par cancer. Longtemps dominé par la génétique, le paradigme du cancer colorectal a récemment évolué laissant une place prépondérante aux facteurs environnementaux. Il est néanmoins difficile d’étudier l’impact de l’environnement sur la carcinogénèse colorectale de façon exhaustive compte tenu de la multiplicité de ces facteurs environnementaux. Dans la présente étude, nous avons essayé d’appréhender la contribution de la composition du microbiote intestinal, de la composition métabolomique des eaux fécales et des altérations épigénétiques de l’hôte comme témoin de ces facteurs environnementaux au cours de la carcinogénèse colorectale et d’en évaluer le bénéfice en tant que marqueur diagnostique non invasif. Nous avons ainsi pu montrer au sein d’une population de patients à risque moyen de cancer colorectal qu’il existait une signature microbiologique, métabolomique et épigénétique spécifique du cancer colorectal. Nous avons également pu montrer que ces marqueurs présentaient des performances diagnostiques supérieures au test colorimétrique au guaiac utilisé dans le dépistage organisé du cancer colorectal. / Colorectal cancer (CRC) is a significant cause of morbidity and mortality in developed countries. The majority of CRC are called sporadic, meaning they are due to environmental factors rather than constitutional genetic alterations. Indeed, the role of environment, i.e. western lifestyle, is also underlined by dramatic geographic variations in CRC incidence in both sexes. However, it is difficult to take into account the totality of human environmental exposures for a better understanding of the colorectal cancer pathogenesis. In the present work, we tried to highlight the contribution of the environment in the development of colorectal cancer by studying the role of the intestinal microbiota together with the role of the fecal metabolites and the presence of epigenetic alterations of the host. We also investigated the performance accuracy of the latter changes for colorectal cancer diagnosis as compared to the guaiac fecal occult blood test which is widely used as a non-invasive test in several screening program. We demonstrated a specific signature associated with advanced colorectal neoplasia for the intestinal microbiota and the fecal metabolite profile for colorectal cancer as well as a link between colorectal cancer and Wif-1 gene methylation in urine and/or fecal samples. Those specific signatures disclosed higher diagnostic accuracy compared to guaiac fecal occult blood test as colorectal cancer screening test.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2016-01-21T16:51:59Z No. of bitstreams: 1 carlavaleriadealvarengaantunes.pdf: 1487917 bytes, checksum: c0d630797135f7fb32b18c3ae9000d7c (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2016-01-25T18:46:52Z (GMT) No. of bitstreams: 1 carlavaleriadealvarengaantunes.pdf: 1487917 bytes, checksum: c0d630797135f7fb32b18c3ae9000d7c (MD5) / Made available in DSpace on 2016-01-25T18:46:52Z (GMT). No. of bitstreams: 1 carlavaleriadealvarengaantunes.pdf: 1487917 bytes, checksum: c0d630797135f7fb32b18c3ae9000d7c (MD5) Previous issue date: 2014-07-10 / FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais / Anemia de difícil tratamento é uma manifestação clínica comumente observada nos pacientes portadores de doenças inflamatórias intestinais, sendo responsável por prejuízo significativo na qualidade de vida destes pacientes. O objetivo deste estudo foi avaliar, nos pacientes com doença inflamatória intestinal, a prevalência e os fatores de risco da anemia suas possíveis etiologias. Neste estudo de corte prospectivo observacional foram recrutados: 100 pacientes portadores de Doença de Crohn e 100 pacientes portadores de Retocolite ulcerativa, diagnosticados e acompanhados regularmente no Centro de Doenças Inflamatórias Intestinais do Hospital Universitário da Universidade Federal de Juiz de Fora, para avaliação hematológica, bioquímica e imunológica. Foram obtidas amostras de sangue (20 ml) e realizados os seguintes exames em todos os pacientes: hemograma completo, VGM, HGM, CHGM, plaquetas, ácido fólico, vitamina B12, reticulócitos, índice de saturação da transferrina, ferritina, ferro sérico, PCR e VHS. Foram adotados para o diagnóstico de anemia os mesmos critérios da WHO (World Health Organization). Foi considerado Anemia por Deficiência de Ferro quando houve diminuição dos níveis séricos de ferro (< 37 μg/dl para mulheres e < de 59 μg/dl para homens), da ferritina (<30μg/l- na ausência de dados clínicos, laboratoriais ou endoscópicos de inflamação intestinal e < 100 μg/l - na presença de quaisquer destes dados), do índice de saturação da transferrina (<16%). Foi considerado Anemia da Doença Crônica quando houve diminuição dos níveis séricos de ferro (< 37 μg/dl para mulheres e < de 59 μg/dl para homens), aumento da ferritina (>100μg/l) e diminuição do índice de saturação da transferrina (<16%). - na presença de dados clínicos, laboratoriais ou endoscópicos de inflamação intestinal e Anemia Mista quando houve diminuição dos níveis séricos de ferro (< 37 μg/dl para mulheres e < de 59 μg/dl para homens) e ferritina entre 30 e 100μg/l. As anemias foram classificadas em hiporregenerativas quando a contagem absoluta de reticulócitos estava abaixo de 50000 e normoproliferativas ou normorregenerativas quando a contagem absoluta de reticulócitos estava acima de 100000/mm³. / Anemia difficult to treat is a clinical manifestation commonly seen in patients with inflammatory bowel disease , being responsible for significant impairment in quality of life of these patients. The aim of this study was to evaluate, in patients with inflammatory bowel disease, the prevalence and factors risk of anemia and possible etiologies of anemia in their possible occurrence. In this cross-sectional study of adult patients with inflammatory bowel disease (IBD) were recruited, of which: 100 patients with Crohn's disease and 100 patients with ulcerative colitis, diagnosed and regularly followed at the Center for Inflammatory Bowel Diseases , University Hospital, Federal University of Juiz de Fora , for haematological, biochemical and immunological evaluation. Blood samples ( 20 ml ) were obtained and the following examinations were performed in all patients: CBC, MCV, MCH , CHCM , platelets , folic acid, vitamin B12 , reticulocytes , transferrin saturation index , ferritin , serum iron, CRP and ESR . For the diagnosis of anemia the same criteria of WHO (World Health Organization) were adopted . Was considered Iron Deficiency Anemia when there was a decrease in serum iron levels ( < 37 mg / dl for women and < 59 g / dl for men ) , ferritin (< 30μg/l - in the absence of clinical, laboratory data or endoscopic intestinal inflammation and <100 mg / l - in the presence of any of these data) , the ratio of transferrin saturation (<16 %). Anemia was considered the Crohnic Disease Anemia when there was a decrease in serum iron levels (< 37 mg / dl for women and < 59 g / dl for men), elevated ferritin ( > 100μg / l ) and decreased transferrin saturation index (<16 %). - in the presence of clinical, laboratory and endoscopic data of intestinal inflammation and Mix Anemia when there was a decrease in serum iron levels ( < 37 mg / dl for women and < 59 g / dl for men) and ferritin between 30 and 100μg / l . Anemia were classified into hiporregenerative when absolute reticulocyte count was below 50,000 and normoproliferative or normorregenerative when the absolute reticulocyte count was above 100,000.

Hintergrund: Patienten mit chronischen entzündlichen Erkrankungen sind aufgrund ihrer Grundkrankheit, aber auch durch die häufig notwendige immunsuppressive Therapie gefährdet, an einer impfpräventablen Infektionskrankheit zu erkranken. In einer Stichprobe sollte der Impfstand bei Patienten mit chronisch-entzündlichen Darmerkrankungen (CED) erhoben werden. Besondere Beachtung galt Vorbehalten der Patienten gegen die empfohlenen Schutzimpfungen. Methoden: Wir baten 203 Patienten mit CED (davon 57% Mb. Crohn, 63% weiblich; medianes Alter 36 Jahre), die im letzten Jahr keine Impfberatung erhalten hatten, einen Fragebogen mit 38 Fragen zu beantworten. Zudem wurden alle Impfnachweise erfasst und mit den aktuellen Empfehlungen der Ständigen Impfkommission abgeglichen. Die Befragung erfolgte vom 1.4. bis 30.9.2009. Ergebnisse: Nur 83% der Patienten hatten einen Impfausweis. Es fanden sich erhebliche Impfdefizite; so wurden in den letzten zehn Jahren nur 67% der Patienten gegen Tetanus und 21% gegen Pertussis geimpft, 28% nahmen die Impfung gegen die saisonale Grippe 2008 wahr und nur 9% wurden jemals gegen Pneumokokken geimpft. Im Subgruppenvergleich von Patienten mit TNF-Blockern (n=39) mit denjenigen Patienten, die noch nie eine immunsuppressive Dauertherapie erhielten (n=67), zeigten sich keine Unterschiede. 80% der Patienten wären bereit, alle offiziell empfohlenen Schutzimpfungen durchführen zu lassen. 22% aller Patienten gaben an, Schutzimpfungen zu vermeiden, weil sie Nebenwirkungen befürchteten, 15% weil das Immunsystem „nicht intakt“ ist und 9% befürchten eine Verschlimmerung der CED durch eine Impfung. Schlussfolgerungen: Der Impfstand in der untersuchten Stichprobe war unzureichend. Es fand sich insbesondere eine deutliche Diskrepanz zwischen der hohen Bereitschaft der Patienten, Schutzimpfungen durchführen zu lassen, und dem tatsächlichen Impfstand. Unsere Daten legen die Notwendigkeit einer erhöhten ärztlicher Wachsamkeit für Impflücken bei immunsuppressiv behandelten Patienten nahe. / Background: Patients with chronic inflammatory diseases are at increased risk for vaccine preventable infectious diseases. This is caused by the inflammatory state itself as well as often necessary immunosuppressive therapy. In a random sample, we investigated whether patients with inflammatory bowel disease (IBD) are sufficiently vaccinated. Special attention was spent to arguments for vaccine refusal. Methods: Between 1.4.2009 and 30.9.2009, we asked 203 consecutive IBD patients (thereof 57% Crohn’s disease, 63% female; median age 36 years), who got no vaccination advise within the last year to answer a questionnaire with 38 questions. As well, the vaccination cards were adjusted with the official recommendations. Results: Only 83% of patients had a vaccination card. We recognized substantial vaccination deficiencies. Within the past 10 years, only 67% of patients had tetanus and 21% had pertussis vaccination. Only 28% had an influenza vaccination in 2008 and only 9% were ever immunized against pneumococcus. A subgroup analysis of patients with TNF-blockers (n=39) with patients, who never had immunosuppressive therapy (n=67) revealed no difference. 80% of all patients are willing to adhere to all officially recommended vaccinations. 22% and 15% of patients stated that they avoid vaccinations as they afraid side effects or as they assess their immune system as not intact. Nine per cent feared a worsening of IBD after vaccination. Conclusions: In this random sample, the adherence to vaccination recommendations was low. We observed a marked difference between the willingness of IBD patients for immunizations and the realized vaccinations. Our data suggest that an increased medical awareness for vaccination deficiencies in immunosuppressed patients is mandatory.

Bakgrund: Inflammatoriska tarmsjukdomar är samlingsnamnet för Crohns sjukdom och Ulcerös kolit. Insjuknandet sker i 20–30 års ålder och sjukdomen är vanligast i västvärlden. Skillnaden mellan varianterna är lokalisation, symtom och riskfaktorer. Sjukdomen är kronisk och därför har omvårdnaden en särskilt betydelsefull roll främst för att skapa goda förutsättningar för att leva med och inte kämpa emot sjukdomen. Syfte: Att beskriva personers upplevelser av inflammatorisk tarmsjukdom. Metod: Metoden som har använts är en litteraturöversikt som är baserad på originalartiklar från kvalitativa studier funna ur databaserna Cinahl Complete och PubMed. Vetenskapliga artiklar som svarade på litteraturöversiktens syfte har analyserats och syntetiserats för att svara på syftet. Resultat: De 10 valda vetenskapliga artiklarna resulterade i fyra kategorier vilka är: Sociala begränsningar och isolering, Relationernas betydelse, Ändå en mening med livet och acceptans samt Arbets-och studierelaterade konsekvenser. Sammanfattning: Till följd av sjukdomen upplevde personer med IBD ett begränsat vardagligt liv, socialt liv och ekonomiska problem. Planering av vardagen har varit mycket tids- &amp; energikrävande. Personerna upplevde inte enbart negativa konsekvenser utan sjukdomen medförde att de fick se livet på ett positivt sätt, hittade mening med livet och förbättrade sin livskvalitet. Sjuksköterskans stödjande roll har varit att skapa en god vårdrelation utifrån ett personcentrerat förhållningssätt och  tillgodose deras vårdbehov. / Background: Inflammatory bowel diseases are a term used to describe Crohns disease and ulcerative colitis. Patients who develop IBD are usually diagnosed between the age of 20 - 30 years old and it is most common in western countries. The difference between Crohns disease and ulcerative colitis are the location in the bowels, symptoms and risk factors. IBD is a chronic disease and should therefore be treated accordingly to relieve symptoms and prevent them from returning. Aim: To describe the experience of inflammatory bowel disease. Method: The method that has been used is based on a literature review from original  articles of qualitative studies found in Cinahl complete and PubMed databases. The scientifical articles also responded to the purpose of the literature review which has been analysed and incorporated to answer the purpose. Results: The 10 different scientific articles have been selected to be used and then divided into four different categories which are the following: social limitations and isolation, importance of relationships, meaning of life and acceptance, and work- and study related consequences. Conclusion: As a result of the disease, people with IBD experienced a limited everyday life, social life and financial problems. Planning everyday life has been very time and energy consuming. The people not only experienced negative consequences, but the disease meant that they got to see life in a positive way, found meaning in life and improved their quality of life. The nurse's supportive role has been to create a good care relationship based on a person-centered approach and meet their care needs.

Commercial and homemade diets are currently used to treat many canine patients with acquired disorders of the colon. Clinically, the efficacy of diets has been found to be unpredictable. Only one study to date has evaluated the effect of diet on the colonic mucosa. This study showed that diet did not observably alter the colonic mucosa of normal dogs, when biopsy samples were evaluated by light microscopy. The effect of diet on colonic ultrastructure in the dog, using transmission electron microscopy, has not previously been investigated. To determine the effect of diet on colonic ultrastructure, cell height, cell area, microvillus height, number of microvilli/apex width and basement membrane width were measured. Ten cells per animal were evaluated. Six dogs were assigned to the control group and fed the control diet for the duration of the study. Six dogs were fed each of the three test diets at four week intervals. The test diets used included a high fiber diet, a hypoallergenic diet and a highly digestible diet. These diets were selected because they are the diets most often recommended for the canine patient with colonic disorders. The value for cell height for the highly digestible group was significantly greater than the other groups, as measured by ANOV A and Duncan's multiple comparison test. No other significant differences were found. The biological relevance of a significantly different value for cell height alone is difficult to evaluate, as other parameters that would indicate an alteration in maturation or proliferation of the colonic epithelial cells did not change. value for cell height alone is difficult to evaluate, as other parameters that would indicate an alteration in maturation or proliferation of the colonic epithelial cells did not change. Therefore, we conclude that commercial diets do not have an effect on the colonic ultrastructure of normal dogs. Although no effect of diet was found, this study does provide morphologic measurements that can be used as a basis for future ultrastructural studies of the colonic mucosa. / Master of Science

La maladie de Crohn (MC) et la colite ulcéreuse (CU) sont des maladies inflammatoires chroniques du tube digestif qu’on regroupe sous le terme maladies inflammatoires de l’intestin (MII). Les mécanismes moléculaires menant au développement des MII ne sont pas entièrement connus, mais des études génétiques et fonctionnelles ont permis de mettre en évidence des interactions entre des prédispositions génétiques et des facteurs environnementaux - notamment la flore intestinale – qui contribuent au développement d’une dérégulation de la réponse immunitaire menant à l’inflammation de la muqueuse intestinale. Des études d’association pangénomiques et ciblées ont permis d’identifier plusieurs gènes de susceptibilité aux MII mais les estimations de la contribution de ces gènes à l’héritabilité suggèrent que plusieurs gènes restent à découvrir. Certains d’entre eux peuvent se trouver dans les régions identifiées par des études de liaison génétique. L’objectif de mon projet de doctorat était d’identifier un ou des facteurs de risque génétique dans la région chromosomale 19p (identifiée comme région de liaison IBD6) et de le/les caractériser au niveau fonctionnel. Nous avons d’abord entrepris une cartographie d’association de la région 19p. À la suite du génotypage successif de deux cohortes indépendantes, nous avons identifié un SNP intronique et quatre SNP codants dont un non-synonyme, rs8108738, tous localisés dans le gène microtubule associated serine threonine kinase gene-3 (MAST3) et associés aux MII. Peu d’information fonctionnelle sur MAST3 était disponible. Par contre MAST2, une protéine encodée par un gène de la même famille, régule l’activité du facteur de transcription inflammatoire NF-kappaB. Nous avons confirmé l’implication de MAST3 dans l’activité de NF-kappaB via un knockdown de MAST3 et des essais gène-rapporteur. Pour poursuivre la caractérisation fonctionnelle de MAST3, nous avons choisi une approche non ciblée pour étudier les effets de la variation des niveaux d’expression de MAST3 sur la cellule. C’est-à-dire que nous avons créé un 1er modèle cellulaire de surexpression du gène MAST3 dans les cellules HEK293 et analysé l’expression pangénomique endogène. La validation de l’expression génique dans un 2e modèle cellulaire de knockdown et de type cellulaire différent (THP1), nous a permis d’identifier et de contrer les effets non-spécifiques dus aux niveaux non-physiologiques. Notre étude d’expression a mené à l’identification d’un groupe de gènes dont l’expression est régulée par MAST3. Ces gènes sont majoritairement impliqués dans des fonctions immunitaires (cytokines pro-inflammatoires, régulateurs de NF-kappaB, migration cellulaire, etc.) et une forte proportion est régulée par NF-kappaB. Nous avons évalué l’importance du groupe de gènes régulés par MAST3 dans la présentation clinique des MII à travers des études d’expression dans des biopsies intestinales de patients atteints de CU. Nous avons constaté que l’expression de ces gènes est significativement supérieure dans les régions enflammées par rapport aux régions saines de la muqueuse intestinale des patients atteints de CU. Globalement, les résultats de nos études suggèrent que le facteur de risque aux MII MAST3 agit via la voie du facteur de transcription NF-kappaB pour influencer l’expression d’un groupe de gènes impliqués dans l’inflammation intestinale typique des MII. Chaque étude génétique sur les MII a le potentiel d’orienter les recherches fonctionnelles vers de nouvelles voies biologiques causales. Le dévoilement des mécanismes moléculaires sous-jacents à ces voies permet d’augmenter les connaissances sur le développement de ces maladies vers une compréhension plus complète de la pathogenèse qui permettra d’optimiser le diagnostic et le traitement de ces maladies. / Inflammatory bowel diseases (IBD) refer to different chronic inflammatory diseases of the digestive tract mainly Crohn’s disease (CD) and ulcerative colitis (UC). Mechanisms leading to the pathogenesis of IBD are not completely understood, but genetic and functional studies have highlighted interactions between genetic predispositions and environmental factors, such as the intestinal microbiota, as contributors to the deregulation of the immune response that leads to inflammation of the intestinal mucosa. Genome-wide and targeted association studies have identified several IBD susceptibility genes. However, estimations of the contribution of these genes to heritability of the disease suggest that more are to be discovered. Some of these genes may be in previously identified IBD linkage regions. The objective of my doctoral project was first, to identify risk factors in the 19p chromosomal region (IBD6), previously identified following a genome-wide linkage study, then to characterise them functionally. We first performed a comprehensive association mapping study of the 19p region. Our two-stage genotyping strategy led to the identification of one intronic SNP and four coding SNP –including one non-synonymous SNP, rs8108738 – all located in the microtubule associated serine threonine kinase gene 3 (MAST3) and associated to IBD. Very limited functional information on MAST3 was available at that time. However MAST2 (a gene in the same family as MAST3), is involved in the regulation of inflammation master switch, transcription factor NF-B. We confirmed the involvement of MAST3 in the modulation of NF-B via a knockdown of MAST3 and gene reporter assays. In order to further characterize the function of MAST3, we chose a non-targeted approach to study the effects of the modulation of MAST3 levels on the cell. More specifically, we created a 1st cell model of MAST3 overexpression in HEK293 cells and analysed the resulting genome-wide endogenous gene expression. Validation in a 2nd cell model consisting of a knockdown of MAST3 in THP1 cells, allowed to identify non-specific gene expression due to non-physiological MAST3 levels. Our expression study led to the identification of a group of genes whose expression is modulated by MAST3. These genes are mainly involved in immune functions (pro-inflammatory cytokines, NF-B regulation, cellular migration, etc) and a majority is regulated by transcription factor NF-B. We evaluated the importance of this MAST3-regulated gene set in the clinical manifestation of IBD through an expression study on biopsies of UC patients. We found that the expression the MAST3-regulated gene set was significantly enriched in inflamed region of the intestinal mucosa of UC patients compared to healthy region. Taken together, the results of our study suggest that IBD risk factor MAST3 acts on the NF-B pathway to influence the expression of a group of genes involved in intestinal inflammation typical of IBD. Every genetic study on IBD has the potential to lead functional research towards new causal biological pathways. The unravelling of the molecular mechanisms underlying these pathways aims to improve the comprehension of the pathogenesis of IBD and hopefully will allow for optimization of diagnostic and treatment of these diseases.

Les maladies inflammatoires de l’intestin (MIIs, [MIM 266600]) sont caractérisées par une inflammation chronique au niveau du tube gastro-intestinal. Les deux principales formes sont la maladie de Crohn (MC) et la colite ulcéreuse (CU). Les MIIs résulteraient d’un défaut du système immunitaire et de l’épithélium intestinal. Ce dernier forme une barrière physique et biochimique qui sépare notre système immunitaire des microorganismes commensaux et pathogènes de la microflore intestinale. Un défaut dans la barrière épithéliale intestinale pourrait donc mener à une réponse immunitaire soutenue contre notre microflore intestinale. Les études d’association pangénomiques (GWAS) ont permis d’identifier 201 régions de susceptibilité aux MIIs. Parmi celles-ci, la région 1q32 associée à la MC (p<2x10-11) et à la CU (p<6x10-7) contient 4 gènes, dont C1orf106, un gène codant pour une protéine de fonction inconnue. Le re-séquençage de la région 1q32 a permis d’identifier une variante génétique rare de C1orf106 (MAF˂1%) associée aux MIIs (p=0,009), Y333F. Nous avons démontré que la substitution de la tyr333 par une phénylalanine semble avoir un effet sur la stabilité protéique de C1orf106 tel que démontré lors de l’inhibition de la synthèse protéique induite par le cycloheximide. Nous avons déterminé que C1orf106 est exprimé dans le côlon et l’intestin grêle. De plus, son expression est augmentée lors de la différenciation des cellules épithéliales Caco-2 en épithélium intestinal polarisé. Son profil d’expression correspond aux types cellulaires et tissulaires affectés dans les MIIs. De plus, C1orf106 est partiellement co-localisée avec le marqueur des jonctions serrées, ZO-1. Toutefois, son marquage reproduit parfaitement celui du marqueur des jonctions adhérentes, E-cadhérine. Les jonctions serrées et adhérentes sont localisées du côté apical de la jonction intercellulaire et sont toutes deux impliquées dans l’établissement de la barrière épithéliale. Nous avons donc testé l’impact de C1orf106 sur la perméabilité de l’épithélium intestinal. Nous avons observé une augmentation de la perméabilité épithéliale chez un épithélium intestinal formé par des cellules Caco-2 sous-exprimant C1orf106. Nos résultats suggèrent que C1orf106 pourrait être le gène causal de la région 1q32. / The Inflammatory bowel diseases (IBD, [MIM 266600]) involve chronic inflammation of the digestive tract and include ulcerative colitis (UC) and Crohn’s disease (CD). IBD may result from defects in the homeostasis of immune system and intestinal epithelium. The latter forms a physical and biochemical barrier to commensal and pathogenic microorganisms. A dysfunction in the epithelial barrier may lead to a sustained immune response against the gut flora. Genome wide association studies (GWAS) have identified 200 susceptibility regions in IBD. Among these, the 1q32 region associated with risk of both CD (p<2x10-11) and UC (p<6x10-7), contains the gene C1orf106. Our targeted re-sequencing study has identified a low-frequency variant, Y333F (p=0.009) in C1orf106, a protein of unknown function and in which tyrosine333 is predicted to be phosphorylated. We demonstrated that its substitution by a phenylalanine may have an effect on C1orf106 protein stability as shown by cycloheximide treatment experiments. Our RNA expression analyses of human tissues and cell lines demonstrated that C1orf106 is mostly expressed in the small intestine and colon. It is also detectable in monocytic cell lines but more highly expressed in colonic epithelial cell lines. Furthermore, its expression is increased by 40% during differentiation of colonic epithelial Caco-2 cells into polarized epithelium. To provide further biological context, we generated colorectal LS174T cells that stably overexpress the Y333F alleles and demonstrated that it is partially localized with ZO-1, used as a tight junction (TJ) marker. We did observe tighter colocalization with E-cadherin, a canonical marker for adherens junctions (AJ), typically located below the TJ complex. AJ and TJ play an essential role in the establishment of epithelial barrier. The localization of C1orf106 at these regions suggests its possible implication in epithelial barrier homeostasis. Using trans-epithelial measurement of ions movement across epithelium, we demonstrated an increased in permeability of an epithelium formed by C1orf106 knock-down Caco-2 cells. Our results suggest that C1orf106 could be the causal gene of the 1q32 susceptibility region.