Submitted by admin tede (tede@pucgoias.edu.br) on 2018-02-16T11:14:27Z No. of bitstreams: 1 Ana Paula da Silva Azevedo Nora Bezerra.pdf: 347105 bytes, checksum: 0bac0a537c9ddd9ba9747d8e5e69562f (MD5) / Made available in DSpace on 2018-02-16T11:14:27Z (GMT). No. of bitstreams: 1 Ana Paula da Silva Azevedo Nora Bezerra.pdf: 347105 bytes, checksum: 0bac0a537c9ddd9ba9747d8e5e69562f (MD5) Previous issue date: 2016-03-22 / Introduction: Even though kidney transplant represents a new perspective to individuals with chronical kidney disease due to its correlation with a better quality of life results and morbimortality indexes, the procedure itself is not free of risks. Vascular complications rates around the world varies from 1 – 23% and it is are also associated with a high risk of kidney graft losses. Objective: To evaluate the incidence of vascular complications among patients submitted to kidney transplant at Santa Casa de Misericórdia de Goiânia on a period of time between January 2013 to December 2014. Material and Methods: It was analyzed 35 files from patients submitted to kidney transplant at Santa Casa de Misericórdia de Goiânia on a period of time between January 2013 and December 2014. It was analyzed the following variables: renal artery stenosis, renal artery thrombosis, renal vein stenosis, renal vein thrombosis, renal artery pseudoaneurysm, arteriovenous fistula, renal artery kinking, kidney graft torsion and kidney infarction. It was also collected data for: kidney graft side, donator´s aspects (alive or deceased), receptor´s age, receptor´s gender, necessity for reintervention and cold ischemia time. Results: It was included 32 patients, 34,38% females and 65,62% males, with median age of 46 years old. Among all surgical complications it was found 3 events of urinary leakage (9,3%), 2 events of retroperitoneal abscess (6,25%), 1 event of kidney graft torsion (3,12%) and 1 event of arterial stenosis (3,12%). All kidney grafts came from deceased donators (100%) and there were no graft losses. Conclusion: Even though the following study had shown a low incidence of vascular complications related with kidney transplant, the TIF more than 24 hours was the only independent risk factor associated with this event. / Introdução: Embora o transplante renal represente uma perspectiva ao indivíduo portador de doença renal crônica terminal por se correlacionar a melhores índices de qualidade de vida e de morbimortalidade, este procedimento não é isento de riscos. As taxas de complicações vasculares variam em todo mundo de 1 – 23% e guardam importância por estar associadas a elevado risco de perda do enxerto. Objetivo: Avaliar a incidência de complicação vascular em pacientes submetidos a transplante renal na Santa Casa de Misericórdia de Goiânia no período entre janeiro de 2013 a dezembro de 2014. Material e Métodos: Foram analisados 35 prontuários de pacientes submetidos a transplante renal na Santa Casa de Misericórdia de Goiânia no período de Janeiro de 2013 a Dezembro de 2014. Foram analisadas as seguintes variáveis: estenose de artéria renal, trombose de artéria renal, estenose de veia renal, trombose de veia renal, pseudoaneurisma de artéria renal, fístula arteriovenosa, kinking de artéria renal, torção de enxerto e infarto. Foi coletado em prontuário: rim transplantado, tipo de doador, idade do receptor, gênero do receptor, reinternação, tempo de isquemia fria. Resultados: A população estudada incluiu 32 pacientes, sendo 34,38% do sexo feminino e 65,62% do sexo masculino, com média de idade de 46 anos. Entre as complicações cirúrgicas, ocorreram 3 casos de fistula urinária (9,3%), 2 casos de coleção (6,25%), 1 caso de torção de enxerto (3,12%) e 1 caso de estenose arterial (3,12%). Todos os enxertos (100%) foram de doador falecido e não houve perda de enxerto em nenhum caso (0%). Conclusões: Embora o presente estudo tenha observado uma baixa incidência de complicação vascular relacionada a transplante renal, o TIF superior a 24hs foi o único fator de risco independente associado a tal evento (p=0,034).

The thesis ``Quality of life in patients with chronic disease of musculoskeletal system`` is divided into two parts. The theoretical part deals with quality of life in general, its assessment, with chronic diseases of musculoskeletal system and their impact on quality of life. The objective of the thesis is stated and hypotheses are set in the practical part by means of which the research itself was started. The following chapter ``Methodology{\crqq} describes the research technique and methods used to confirm or disprove given objective and hypotheses stated. The next chapter ``Results{\crqq} contains charts and graphs with final values and their verbal description. Information obtained from the research is confronted in the discussion.

As dificuldades associadas à coleta de urina de 24h e à baixa credibilidade do uso do biomarcador na prática clínica para estimar a ingestão de proteína de pacientes com doença renal crônica (DRC) na fase não-dialítica sinalizam para busca de alternativas acuradas e de ampla acessibilidade para a descrição do consumo de proteína nessa população. Avaliar a acurácia de métodos de inquérito dietético para estimar o consumo de proteína em pacientes de DRC na fase não dialítica e, a concordância desses com o biomarcador de ingestão protéica. Também foi avaliado a concordâncias entre o registro alimentar (RA) e recordatório alimentar de 24 horas (Rec24h). Cento e vinte e dois pacientes com DRC na fase não dialítica, que atenderam aos critérios de elegibilidade, foram submetidos à avaliação antropométrica, laboratorial e, tiveram a ingestão de proteína estimada por três métodos de avaliação do consumo alimentar, sendo estes dois métodos de inquérito dietético e um método de biomarcador. Os métodos de inquéritos alimentares compreenderam 4 dias de RA e 2 dias de Rec24h. Para o biomarcador foi avaliado a excreção de nitrogênio uréico em uma amostra de urina de 24 horas, o qual foi utilizado em equação do equivalente protéico do aparecimento do de nitrogênio uréico (PNA). Na análise estatística dos métodos de inquérito dietético, utilizou-se o PC-Side para estimar a variabilidade da ingestão de proteína, equações para estimar o número de dias necessários para estimativas acuradas da ingestão de proteína em avaliações no nível individual e coletivo. Para avaliar a concordância entre os três métodos de avaliação do consumo de proteína, utilizou-se o Concordance correlation coefficient (CCC) e o gráfico de Bland & Altman. Resultados: Os 4 dias de RA e 2 Rec24h descreveram com acurácia elevada a ingestão de proteína no nível coletivo, sendo respectivamente de 0,85 e 0,73. Para o nível individual, com erro tolerado intermediário de 20% (acurácia de 0,8), foram necessários 6 dias de RA e 5 de Rec24h para avaliação do consumo de proteína. Ao avaliar a concordância entre o PNA com o RA e Rec24h, observou-se CCC reduzido (< 0,3). Da mesma forma, ao avaliar a dispersão individual das diferenças obtidas entre o PNA e RA e Rec24h pelo gráfico de Bland & Altman, notou-se valores amplos de limite de concordância. Por outro lado, valores mais elevados de CCC (>0,4) foram encontrados entre o RA e o Rec24h. O gráfico de Bland & Altman desses dois métodos mostrou menor dispersão. Contudo, essa melhor concordância pode ser decorrente de superestimação da correspondência entre os métodos. Além disso, a concordância reduzida observada entre o PNA e o RA e Rec24h não permitiram afirmar que os métodos de inquéritos dietéticos ofereçam medidas irreais da ingestão de proteína, nem tampouco foi possível afirmar que a medida real é aquela sugerida pelo PNA. Em pacientes com DRC na fase não dialítica, orientada a seguir dieta hipoprotéica, o RA e Rec24h podem ser usados em substituição ao uso PNA como alternativas de baixo custo e de ampla acessibilidade à prática clínica para descrever a ingestão de proteína, desde que sejam definidos o nível da avaliação, o número ideal de dias e a acurácia desejada. / It has been well described in the literature the errors inherent to the 24 hours urine collection in free-living individuals. Therefore, the assessment of protein intake in nondialyzed chronic kidney disease (CKD) patients by the urinary urea excretion in the 24 hour urine sample, may lead to important errors related to the method itself. In this regard, assessing surrogate methods is of high relevance. To evaluate the accuracy of the dietary methods to estimate the protein consumption in nondialyzed CKD patients and also to assess the agreement between a biomarker of protein intake and dietary methods. In addition, it was also evaluated the agreement between two dietary methods. One hundred and twenty-two nondialyzed CKD patients, who met the eligibility criteria, were included. All participants underwent to antropometric and laboratory assessments, and had the protein intake estimated by three methods: two methods of dietary intake and one dietary biomarker. The dietary intake comprised 4 days of food records (FRec) and 2 days of 24-hour food recall (24hFRecall). For the biomarker, it was evaluated the urinary urea nitrogen excretion in a 24 hours urine sample, which was used in the equation of the protein equivalent of nitrogen appearance (PNA). The software PC-Side was used to estimate the variability of the protein intake in the FRec and 24hFRecall. In addition, specific equations were used to assess the number of days needed to estimate the protein intake with high accuracy in the individual and collective level. In order to evaluate the agreement between the 3 methods, it was used the concordance correlation coefficient (CCC) and the Bland & Altman plot analysis (1986). In the collective level, 4 days FRec and the 2 days of 24hFRecall described the protein intake with an accuracy close the highest acceptable level, being of respectively 0.85 and 0.73. For the individual level, by accepting an intermediate tolerated error of 20% (accuracy 0.8), 6 days of FR and 5 days of 24hFR were needed for the assessment of protein intake. When assessing the agreement between the PNA and the FRec and 24hFRecall, it was observed reduced CCC (< 0.3). Likewise, when evaluating the individual differences obtained between the PNA and the FRec and 24hFRecall by the Bland & Altman plot analysis, it was observed a wide concordance limit, which is consistent with the low concordance observed between the methods. Moreover, higher values of CCC (> 0.4) were found between the FRec and 24hFRecall. The Bland & Altman plot analysis of these two methods showed more narrows differences, which is consistent with the higher CCC observed. However, this best agreement may be due to an overestimation between the methods. Furthermore, the reduced concordance observed between the PNA and the FRec and 24hFRecall does not mean that the dietary intake methods give biased or unrepresentative measurements of protein intake, nor was that the PNA gave unbiased measurements of protein intake. FRec and 24hFRecall can be used as surrogate methods for the PNA, as an alternative low cost and high applicability method in the clinical routine practice to describe the protein intake.

As dificuldades associadas à coleta de urina de 24h e à baixa credibilidade do uso do biomarcador na prática clínica para estimar a ingestão de proteína de pacientes com doença renal crônica (DRC) na fase não-dialítica sinalizam para busca de alternativas acuradas e de ampla acessibilidade para a descrição do consumo de proteína nessa população. Avaliar a acurácia de métodos de inquérito dietético para estimar o consumo de proteína em pacientes de DRC na fase não dialítica e, a concordância desses com o biomarcador de ingestão protéica. Também foi avaliado a concordâncias entre o registro alimentar (RA) e recordatório alimentar de 24 horas (Rec24h). Cento e vinte e dois pacientes com DRC na fase não dialítica, que atenderam aos critérios de elegibilidade, foram submetidos à avaliação antropométrica, laboratorial e, tiveram a ingestão de proteína estimada por três métodos de avaliação do consumo alimentar, sendo estes dois métodos de inquérito dietético e um método de biomarcador. Os métodos de inquéritos alimentares compreenderam 4 dias de RA e 2 dias de Rec24h. Para o biomarcador foi avaliado a excreção de nitrogênio uréico em uma amostra de urina de 24 horas, o qual foi utilizado em equação do equivalente protéico do aparecimento do de nitrogênio uréico (PNA). Na análise estatística dos métodos de inquérito dietético, utilizou-se o PC-Side para estimar a variabilidade da ingestão de proteína, equações para estimar o número de dias necessários para estimativas acuradas da ingestão de proteína em avaliações no nível individual e coletivo. Para avaliar a concordância entre os três métodos de avaliação do consumo de proteína, utilizou-se o Concordance correlation coefficient (CCC) e o gráfico de Bland & Altman. Resultados: Os 4 dias de RA e 2 Rec24h descreveram com acurácia elevada a ingestão de proteína no nível coletivo, sendo respectivamente de 0,85 e 0,73. Para o nível individual, com erro tolerado intermediário de 20% (acurácia de 0,8), foram necessários 6 dias de RA e 5 de Rec24h para avaliação do consumo de proteína. Ao avaliar a concordância entre o PNA com o RA e Rec24h, observou-se CCC reduzido (< 0,3). Da mesma forma, ao avaliar a dispersão individual das diferenças obtidas entre o PNA e RA e Rec24h pelo gráfico de Bland & Altman, notou-se valores amplos de limite de concordância. Por outro lado, valores mais elevados de CCC (>0,4) foram encontrados entre o RA e o Rec24h. O gráfico de Bland & Altman desses dois métodos mostrou menor dispersão. Contudo, essa melhor concordância pode ser decorrente de superestimação da correspondência entre os métodos. Além disso, a concordância reduzida observada entre o PNA e o RA e Rec24h não permitiram afirmar que os métodos de inquéritos dietéticos ofereçam medidas irreais da ingestão de proteína, nem tampouco foi possível afirmar que a medida real é aquela sugerida pelo PNA. Em pacientes com DRC na fase não dialítica, orientada a seguir dieta hipoprotéica, o RA e Rec24h podem ser usados em substituição ao uso PNA como alternativas de baixo custo e de ampla acessibilidade à prática clínica para descrever a ingestão de proteína, desde que sejam definidos o nível da avaliação, o número ideal de dias e a acurácia desejada. / It has been well described in the literature the errors inherent to the 24 hours urine collection in free-living individuals. Therefore, the assessment of protein intake in nondialyzed chronic kidney disease (CKD) patients by the urinary urea excretion in the 24 hour urine sample, may lead to important errors related to the method itself. In this regard, assessing surrogate methods is of high relevance. To evaluate the accuracy of the dietary methods to estimate the protein consumption in nondialyzed CKD patients and also to assess the agreement between a biomarker of protein intake and dietary methods. In addition, it was also evaluated the agreement between two dietary methods. One hundred and twenty-two nondialyzed CKD patients, who met the eligibility criteria, were included. All participants underwent to antropometric and laboratory assessments, and had the protein intake estimated by three methods: two methods of dietary intake and one dietary biomarker. The dietary intake comprised 4 days of food records (FRec) and 2 days of 24-hour food recall (24hFRecall). For the biomarker, it was evaluated the urinary urea nitrogen excretion in a 24 hours urine sample, which was used in the equation of the protein equivalent of nitrogen appearance (PNA). The software PC-Side was used to estimate the variability of the protein intake in the FRec and 24hFRecall. In addition, specific equations were used to assess the number of days needed to estimate the protein intake with high accuracy in the individual and collective level. In order to evaluate the agreement between the 3 methods, it was used the concordance correlation coefficient (CCC) and the Bland & Altman plot analysis (1986). In the collective level, 4 days FRec and the 2 days of 24hFRecall described the protein intake with an accuracy close the highest acceptable level, being of respectively 0.85 and 0.73. For the individual level, by accepting an intermediate tolerated error of 20% (accuracy 0.8), 6 days of FR and 5 days of 24hFR were needed for the assessment of protein intake. When assessing the agreement between the PNA and the FRec and 24hFRecall, it was observed reduced CCC (< 0.3). Likewise, when evaluating the individual differences obtained between the PNA and the FRec and 24hFRecall by the Bland & Altman plot analysis, it was observed a wide concordance limit, which is consistent with the low concordance observed between the methods. Moreover, higher values of CCC (> 0.4) were found between the FRec and 24hFRecall. The Bland & Altman plot analysis of these two methods showed more narrows differences, which is consistent with the higher CCC observed. However, this best agreement may be due to an overestimation between the methods. Furthermore, the reduced concordance observed between the PNA and the FRec and 24hFRecall does not mean that the dietary intake methods give biased or unrepresentative measurements of protein intake, nor was that the PNA gave unbiased measurements of protein intake. FRec and 24hFRecall can be used as surrogate methods for the PNA, as an alternative low cost and high applicability method in the clinical routine practice to describe the protein intake.

This master thesis focuses on the integration of adults with multiple sclerosis, and offers a perspective on their quality of life. The theoretical part describes chronic diseases and their impact on the personality of the patients with multiple sclerosis, as well as patients' coping mechanisms. The main part of the thesis is dedicated to definition, progress, epidemiology, symptomatology, diagnostics and therapy of multiple sclerosis. Many patients are forced to change their lifestyle, employment and everyday activities due to multiple sclerosis. Therefore, one chapter of this master thesis is dedicated to the possibilities of their economical, social and cultural integration. In the empirical part, a scientific research was conducted using MSQOL-54 questionnaire, that determined the effect of multiple sclerosis on the patients' quality of life and their mental and physical health. The most significant negative factors impacting the quality of life were pain and fatigue, which are at the same time the most common symptoms occuring in patients with multiple sclerosis. Key words Multiple sclerosis, Chronical disease, Handicap, Integration, Quality of Life, Employment, Culture.

Bakgrund: Personer med en kronisk obstruktiv lungsjukdom kan ha många besvärande symtom. Andnöd är ett betydande symtom som ofta påverkar personernas liv avsevärt och försämrar livskvalitén. Tidigare forskning visar på att personer med en kronisk obstruktiv lungsjukdom inte får palliativ vård i samma utsträckning som personer med andra luftvägssjukdomar. Det kan vara betydande kunskap för sjuksköterskan att förstå patientens upplevelse av att leva med sjukdomen för att kunna bemöta dessa personer på bästa sätt. Syfte: Syftet var att beskriva symtom och utmaningar, utifrån patientens perspektiv, med fokus på palliativ vård hos personer med kronisk obstruktiv lungsjukdom.  Metod: En litteraturöversikt grundat på 15 vetenskapliga artiklar. Resultat: De huvudteman som kunde utkristallisera sig från dataanalysen var; fysiska symtom, psykiska symtom, hantering av det dagliga livet, information och kommunikation och existentiella utmaningar. Det mest genomgående betydande symtomet i artiklarna var det fysiska symtomet andnöd. Flertalet artiklar konstaterade att deltagarna önskade mer information om sin sjukdom, prognos och vård vid livets slut. De flesta var positiva till att inleda samtal om palliativ vård i ett tidigt skede i sjukdomen.  Slutsats: Att få personer med KOL får palliativa insatser kan bero på att sjukdomsprognosen är så pass oviss att man inte vet när man ska börja ha samtal om den sista tiden i livet. Denna litteraturöversikt visar på att palliativ vård välkomnas av personer med KOL i ett tidigt skede i sjukdomen då de lättare kan acceptera sin situation och besvärliga symtom. / Background: People with chronic obstructive pulmonary disease have several severe symptoms. Shortness of breath is a significant symptom that affects people´s lives considerably and impairs their quality of life. Previous research shows that people with chronic obstructive pulmonary disease do not receive palliative care to the same extent as other. It is important knowledge for the nurse to understand the patients´ experiences of living with the disease to treat these people in the best possible way.  Aim: The aim was to describe the symptoms and challenges, through patient´s perspective, with emphasis on palliative care in people with chronic obstructive pulmonary disease. Method: A literature review based on 15 scientific articles. Results: The main themes from the data analysis were physical symptoms, psychological symptoms, management of daily life, information and communication and existential support. The most consistently significant symptom in the articles was the physical symptom shortness of breath. Several articles stated that participants wanted more information about their illness, prognosis and care at the end of their lives. Most people were positive about initiating conversations about palliative care at an early stage of the disease. Conclusion: Chronic obstructive pulmonary disease (COPD) affects the person with many troublesome symptoms, regardless of what phase you are in the disease progression. This literature review shows that palliative care is welcomed by people with COPD at an early stage in the disease, because they can more readily accept their situation.

The thesis deals with the topic of ulcerative colitis and its psychosocial impact upon adolescents. The main goal of the thesis is to identify, through qualitative research, the psychosocial factors that influence the adolescent in his everyday life and to map the situations that are most difficult for the teenager. The topic is based on the theoretical part, which consists of information about the diagnosis and course of ulcerative colitis, treatment methods and complications connected with them. The theoretical part also deals with describing the psychosocial factors of ulcerative colitis and describing adolescence as the stage of an individual's life. The research part describes a qualitative research method that answers the main research question. The output of a qualitative research survey is 7 identified areas that are most influenced by ulcerative colitis during adolescence. Key words: Ulcerative colitis, adolescence, psychosocial factors, chronical disease, impact, handicap, social impact

La dépression représente l’affection neuropsychiatrique la plus répandue dans le monde. Son impact socio-économique est important et la prise en charge des patients est souvent confrontée aux limites d’efficacité des traitements actuels. Les mécanismes sous-jacents responsables de cette affection sont en partie inconnus. Néanmoins, un nombre grandissant de données désignent aujourd’hui le microbiote intestinal comme un acteur potentiel de la physiopathologie de la dépression. En particulier, des déséquilibres dans la nature et la quantité des métabolites bactériens qu’il produit pourraient être impliqués. L’indole est un métabolite du tryptophane produit par le microbiote intestinal. Il joue un rôle (i) dans la physiologie bactérienne et les relations bactérie-bactérie au sein du microbiote, (ii) dans le fonctionnement des cellules intestinales, et (iii) certains de ses dérivés sont connus pour être neuro-actifs. L’objectif de la thèse est de mieux comprendre comment un excès de production de ce métabolite bactérien peut influencer le cerveau et le comportement dans le contexte de la dépression et de troubles mentaux qui lui sont souvent associés, les troubles anxieux. Mon travail de thèse comporte 3 parties.La première a pour but de tester si une dysbiose du microbiote intestinal induisant une surproduction d’indole est un facteur de vulnérabilité aux troubles anxieux et dépressifs, et d’étudier les modifications biochimiques et moléculaires associées. Une étude comportementale chez des souris gnotoxéniques produisant de l’indole en excès ou n’en produisant pas montre qu’une surproduction intestinale d’indole exacerbe les comportements de type anxieux et dépressif induits par l’exposition à un stress chronique modéré. L’étude de l’expression de gènes des glandes surrénales impliqués dans la synthèse de la corticostérone et de l’adrénaline montre que les souris surproductrices d’indole et soumises au stress chronique surexpriment un gène impliqué dans la synthèse de l’adrénaline. Des dosages de neurotransmetteurs cérébraux et des analyses d’expression de gènes dans le cerveau et la muqueuse intestinale ont aussi été conduits. La seconde partie de la thèse porte sur l’identification des circuits neuronaux cérébraux activés par l’indole. Pour ce faire, des souris conventionelles ont été gavées avec de l’indole et la protéine c-Fos marquée par immunohistochimie dans toutes les régions du cerveau, du tronc cérébral au cortex préfrontal. La troisième partie de la thèse consiste à moduler la disponibilité du tryptophane alimentaire dans le tube digestif de souris conventionnelles, et à en étudier l’impact sur la composition bactérienne du microbiote intestinal et sa capacité à produire de l’indole. La composition du microbiote fécal des souris a été déterminée par séquençage de l’ADN codant l’ARNr 16S et les concentrations fécales de tryptophane et d’indole ont été déterminées par analyse HPLC.En conclusion, ce projet de thèse aura contribué à une meilleure compréhension du rôle de l’indole dans les réponses comportementales et neuro-endocrines au stress. Il aura également permis d’initier l’étude des circuits neuronaux activés par l’indole, et de tester comment la modulation de la digestibilité de protéines riches en tryptophane peut influencer l’équilibre du microbiote intestinal et ses capacités à produire de l’indole. / Depression is the most spread neuropsychiatric disorder worldwide. It is a socio-economical burden and efficacy of the treatments is very limited. Mechanisms underlying this disorder are mainly unknown. However, a growing number of data has highlighted the potential role of gut microbiota dysbioses in the pathophysiology of depression. Particularly, an unbalance in the diversity and abundance of metabolites produced by the gut microbiota might be implicated. Indole is a tryptophan derivative produced by the gut microbiota. It is known to influence (i) the bacterial physiology and quorum sensing within the gut microbial ecosystem, (ii) the intestinal cells functioning, and (iii) some of its derivatives are known to affect the brain. The aim of this work is to investigate how an overproduction of indole by the gut microbiota can modulate the brain and behaviour in the context of depression and its main co-morbidity, anxiety. This thesis work contains 3 sections.In the first one, we investigated whether an intestinal microbiota dysbiosis leading to an overproduction of indole could confer vulnerability toward anxiety and depression. We also looked for potentially associated biochemical and molecular changes. A behavioural study in gnotobiotic mice overproducing or non producing indole showed the overproduction of indole exacerbated the anxiety-like and depressive-like behaviours induced by a chronic mild stress. Gene expression analysis in the adrenal glands showed chronically stressed mice overproducing indole up-regulated the expression of one gene implicated in adrenaline synthesis. Brain neurotransmitters quantification and gene expression in the brain and intestinal mucosa were also carried out. The second part of the thesis work focused on the brain neurocircuitry of indole. Conventional mice were force-fed with indole and the c-Fos protein was labelled by immunohistochemistry in all brain areas from brainstem to prefrontal cortex. In the third and last part, we modulated dietary tryptophan availability in the gastro-intestinal tract of mice, to study how this modulation could affect the composition and the indole production ability of the gut microbiota. The mice fecal microbiota composition was determined by 16S rRNA sequencing, and fecal tryptophan and indole concentrations were measured by HPLC.In summary, this work improves the understanding of the role of indole in the behavioural and neuro-endocrine responses to stress. This study also initiated the deciphering of brain circuits activated by indole. Finally, it brings some evidence about how modulating food digestibility can impact the gut microbiota composition and its indole production capacity.

Die qualitative Studie befasst sich mit der Lebenslage von (Ehe-)Paaren, welche in ihrer gemeinsamen Zeit als Zweierbeziehung den Eintritt einer sogenannten „Spätbehinderung“ durch plötzliches Krankheits- oder Unfallgeschehen oder aufgrund einer chronischen Erkrankung erleben. Die inhaltliche Fragestellung richtet sich auf die soziale Handlungspraxis partnerschaftlicher Arbeitsorganisation im Zusammenhang mit dem Eintritt einer körperlichen „Behinderung“ sowie auf die partnerschaftliche Deutung von „Körperbehinderung“ im Rahmen der dyadischen Wirklichkeitskonstruktion. In Erweiterung des aktuellen Forschungsstands wird diesbezüglich nicht allein auf die individuelle Sichtweise des „betroffenen Partners“ oder des „angehörigen Partners“ fokussiert, sondern auch die gemeinsame Ebene dyadischer Wirklichkeitskonstruktion miteinbezogen. Die Datengrundlage dieser Studie im Stil der Grounded Theory Methodologie bilden fünfzehn Interviewreihen, bestehend aus einem Paarinterview (narratives Interview) und anschließenden Einzelinterviews (problemzentriertes Interview) mit jedem Partner. Im Ergebnisteil verdeutlichen sieben Fallbeschreibungen die komplexe paarspezifische Bearbeitung einer „Spätbehinderung“ im Rahmen von Biographie, Ressourcen und Körperlichkeit. Theoretisch verdichtet werden die Ergebnisse in einer Konzeption partnerschaftlicher Konstruktion von Behinderung im Kontext von Leiberfahrung und Körperbetrachtung. Die partnerschaftliche Alltagsverhandlung dreht sich im Zuge der Neukonstruktion von Alltag und „Normalität“ um die körperliche Funktionsfähigkeit des Partners mit Beeinträchtigung und verhandelt dessen Veränderung der Körperlichkeit dabei gleichzeitig mit, wobei körperliche, kulturelle, medizinische und sozialpolitische Aspekte in die partnerschaftliche Deutung mit hinein spielen. Zudem berühren derlei Aushandlungen zentrale Grunddefinitionen von Partnerschaft wie Individualitätsentfaltung, Intimität und Privatheit. / This study focusses on the circumstances of marriage and quasi-marital couples, which experience together diability in later couple lifetime by occurence of chronical illness or impairment of one of the couples members. The contentwise question is on one hand targeted at the social practice of work processes and tasks of couples related to the life change through the occurence of impairment. On the other hand the study demands on the couples interpretation of this experience. The data basis consists of fifteen narrative interview cycles each containing one interview with the couple plus one interview with each marriage partner. Here the situation of a suddenly interruption of everyday life through an event of accident or illness has been contrasted with the situation of chronic ailment with its progressing loss of physical power. The study approach of interviewing, analysing and interpretation founds on the principles of the Grounded Theory Methodology. The results are presented twofold. Firstly seven case reconstructions clarify the couple''s coping with physical body change in the context of biography, capabilities and resources, and physicality and illustrate similarities and differences of the couple’s topics. After this a conception of the couple''s construction of reality in the case of an impairment experience were tendered. It describes the couple’s experience of change, disability and normality as a experience of the physical and functional body, which cannot be extricated from cultural and socio-political framing. Specifically, the main topic of the couple’s negotation concern on the one hand the self-activity of the partner with impairment and on the other hand the availability of the other part and his / her duty to compensate for both the lack of paid work and the increasing amount of time spent for everyday life. Significant is the fact that in this process challenge central positions of the couple’s intimacy and privateness.

L’ADOA-1 (Autosomal dominant optic atrophy) est une maladie neurologique pouvant être causée par la mutation de la protéine mitochondriale OPA1 (Optic atrophy type 1) et pouvant conduire à une cécité. Certains patients peuvent présenter un dysfonctionnement mitochondrial plus généralisé, et développer d'autres complications neuromusculaires (ADOA-1+). La protéine OPA1 est une dynamine GTPasique impliquée dans la dynamique mitochondriale en modulant la fusion des membranes internes, et plus largement dans le maintien des fonctions mitochondriales. Le rôle de cette protéine a été étudié dans beaucoup de types cellulaires, mais peu d’études se sont intéressées à la cellule cardiaque qui pourtant possède de nombreuses mitochondries.La 1ère question soulevée par cette thèse était de déterminer l’implication de la protéine OPA1 dans l’organisation du réseau mitochondrial et dans le fonctionnement de la cellule cardiaque en condition physiologique ou pathologique. Pour répondre à cela, nous avons utilisé un modèle murin hétérozygote pour Opa1 (Opa1+/-). Nous avons montré que dans le cardiomyocyte adulte, la diminution d’expression d’OPA1 induisait un déséquilibre de la balance fusion/fission, qui se traduisait par une désorganisation du réseau mitochondrial, ainsi qu’une altération de la morphologie des mitochondries. Cependant, ces modifications n’engendraient pas d’altération des capacités oxydatives des mitochondries, mais conduisaient à une perturbation des propriétés d’ouverture du PTP. En outre, la déficience en OPA1 n’influençait pas la fonction cardiaque en condition physiologique, mais était associée à son altération plus sévère en condition pathologique. La 2nde question de cette thèse était de savoir l’implication d’OPA1 dans la réponse à un stress physiologique des cellules musculaires squelettiques, et ainsi étudier le lien éventuel entre OPA1 et la mise en place de la biogénèse mitochondriale. Nous avons donc soumis nos souris Opa1+/- à un exercice d’endurance. Nos résultats ont révélé que nos deux groupes d’animaux disposaient des mêmes capacités physiques à l’entraînement. L’adaptation des souris Opa1+/- à l’entrainement s’effectuait par un remodelage métabolique, vraisemblablement pour contrer un défaut d’adaptation de la biogénèse mitochondriale. En conclusion, nos résultats ont permis de mieux définir le rôle de la protéine OPA1 dans les muscles striés et son implication dans l’adaptation à un stress. Ce travail nous ouvre des perspectives sur le rôle de la dynamique mitochondriale dans l’adaptation à un stress. / ADOA-1 (Autosomal dominant optic atrophy) is a neurological disease that can be caused by mutations in mitochondrial protein OPA1 (Optic atrophy type 1) and can lead to blindness. Some patients with OPA1 mutations may have a generalized mitochondrial dysfunction, and may develop additional neuromuscular complications (ADOA-1+). OPA1 protein is a GTPase dynamin involved in mitochondrial dynamics by controlling the fusion of inner membranes, and also in the maintenance of mitochondrial functions. The role of this protein has been studied in many cell types, but only few studies have been done on cardiac cell, which nevertheless has many mitochondria.The first question raised by this thesis was to determine the involvement of OPA1 protein in mitochondrial network organization and the functioning of the cardiac cell in physiological or pathological condition. To answer this, we used a mouse model heterozygous for Opa1 (Opa1+/-). We have shown that in adult cardiomyocytes, a decrease expression of OPA1 induces an imbalance fusion/fission, which results in a disruption of mitochondrial network, as well as alteration of the morphology of mitochondria. However, these changes did not alter oxidative capacities, but leads to a disturbance of PTP opening. Additionally, OPA1 deficiency did not affect cardiac function under physiological conditions, but it is associated with a stronger impairment of cardiac function in pathological condition.The 2nd part of this thesis was to determine the involvement of OPA1 in response to physiological stress in cells of skeletal muscle, and thus to study the possible link between OPA1 and mitochondrial biogenesis activation. For this, we submitted our Opa1+/- mice to an exercise training. Our results showed that both groups of animals were able to perform the same physical activity. The adaptation of Opa1+/- mice to training did not involve mitochondrial biogenesis and led to a specific response involving a metabolic remodelling towards higher fatty acids utilization.In conclusion, our results allowed us a better understanding of OPA1 role in striated muscle and its involvement for adaptation to a stress. This work opens new perspectives on the role of mitochondrial dynamics in cardiac and muscle cells and during adaptation to a stress