No description available.

Myxomatous mitral valve disease (MMVD) is the single most common acquired cardiac disease of dogs, and is a disease of significant veterinary importance. It also bears close similarities to mitral valve prolapse in humans and therefore is a disease of emerging comparative interest. Realising the importance of collagen fibres in mitral heart valves and considering the paramount significance of myxomatous mitral valve disease, a better understanding of the pathogenesis of MMVD is essential. Thus, this study was designed to investigate the changes in collagen molecules, including fibril structure, fibril orientation, d-spacing, collagen density, collagen content, thermal stability, and the status of mature and immature crosslinks. A combination of biophysical and biochemical tools such as x-ray diffraction, neutron diffraction, HPLC were utilised in order to fulfil the objectives. Biochemical assay of hydroxyproline revealed a 10% depletion of collagen in mildly affacted (grade I and II) leaflets, while a 20% depletion of fibrillar collagen was revealed by mapping the collagen fibrils onto the anatomy of cardiac leaflets using x-ray data. Differential scanning calorimetry showed that there were no significant differences in the onset temperature of denaturation of collagen between the healthy and affected leaflets. However, in affected areas of leaflets, the enthalpy of denaturation significantly dropped by 20%. In the affected regions, neutron diffraction results showed an increase in the immature reducible cross-links though the low number of the samples can be considered a limiting factor in this regard. However, the HPLC results showed a 25% decrease in the number of mature cross-links. Additionally, the recently introduced imaging technologies to biology and medicine such as differential enhancing imaging (DEI) and coherent anti-Stokes Raman scattering spectroscopy (CARS) were, to the author’s best knowledge, applied for the first time to this disease. In doing so, this thesis furthers our understanding of the pathogenesis of MMVD, especially in relation to the collagen. The thesis provides new findings about MMVD and demonstrates the potential of biophysical tools for studying similar conditions.

Des altérations de fonctions physiologiques du réticulum endoplasmique (RE) induisent un processus appelé stress RE. Dans le domaine cardiovasculaire, plusieurs travaux ont montré que le stress RE contribue au développement de la majorité des pathologies cardiaques. En réponse au stress RE, la réponse UPR (Unfolded Protein Response) est activée afin de restaurer l’homéostasie du RE et de permettre la survie de la cellule. Néanmoins, dans le cas d’un stress RE excessif ou prolongé, les altérations ne pouvant plus être compensées, la cellule est éliminée par apoptose contribuant au développement de la pathologie cardiaque. Une thérapie prometteuse pour lutter contre ce type de pathologie consisterait donc à moduler la réponse au stress RE afin d’inhiber l’apoptose des cardiomyocytes. Au cours de ma thèse, je me suis intéressé aux modifications induites en réponse au stress RE dans le cœur et au rôle de la sirtuine 1 (SIRT1) dans la modulation de cette réponse. SIRT1 est une déacétylase activée par différents stress cardiaques et connue pour favoriser la survie cellulaire. D’une part, j’ai mis en évidence que le stress RE induit une modification importante de l’architecture des cardiomyocytes et en particulier une augmentation des contacts RE/mitochondries associée à une altération de la fonction mitochondriale. D’autre part, en utilisant une lignée cellulaire (H9c2), des cardiomyocytes de rat adulte et des souris invalidées pour SIRT1, j’ai démontré in vitro et in vivo (i) que SIRT1 est activée et joue un rôle cardioprotecteur en réponse au stress RE, (ii) que SIRT1 limite la réponse UPR en régulant spécifiquement la voie PERK, et (iii) que SIRT1 régule la voie PERK en déacétylant le facteur d’initiation de la traduction, eIF2 sur deux résidus lysine. Ces résultats montrent donc pour la première fois que SIRT1 est impliquée dans la régulation de la réponse apoptotique au stress RE des cardiomyocytes et suggèrent que cette déacétylase serait une cible thérapeutique intéressante pour prévenir l’apoptose dans les pathologies cardiaques liées au stress RE. / Impairment of physiological functions of the endoplasmic reticulum (ER) induces the so-called ER stress. ER stress has been implicated in many cardiovascular diseases including ischemic heart, hypertrophy and heart failure. To overcome the deleterious effect of ER stress, an evolutionarily conserved adaptive response known as Unfolded Protein Response (UPR) is activated in order to restore ER homeostasis and promote cell survival. Nevertheless, in the case of prolonged or severe ER stress, apoptotic cell death is ultimately activated to eliminate stressed cells, thus contributing to the development of the pathology. The modulation of ER stress response, in order to reduce cardiomyocyte apoptosis, thus appears as a promising therapeutic strategy for such pathologies. During my Ph.D thesis, I studied the modification that occur during ER stress response in the heart and the role of the sirtuine 1 (SIRT1) in the modulation of this response. SIRT1 is a deacetylase activated in response to many cardiac stresses to promote cell survival. First, we showed that ER stress induces important structural modifications of cardiomyocytes and in particular an increase in contact sites between ER and mitochondria associated with an alteration of the mitochondrial function. Secondly, using a cell line (H9c2), freshly isolated adult rat ventricular cardiomyocytes and SIRT1-KO mice, we demonstrated in vitro and in vivo (i) that SIRT1 is activated and plays a cardioprotective role in ER stress response, (ii) that SIRT1 attenuates the UPR by specifically regulating the PERK pathway, and (iii) that SIRT1 modulates PERK axis by deacetylating the translation initiation factor, eIF2on two lysine residues. Collectively, our results provide the first evidence that SIRT1 modulates ER stress-induced apoptosis in the heart and suggest that this deacetylase may represent a therapeutic target to prevent apoptosis in cardiac pathologies associated to ER stress.

Myxomatous mitral valve disease (MMVD) is one of the most common degenerative cardiac diseases affecting humans and dogs; however, its pathogenesis is not completely understood. This study focussed on developing tissue-engineered fibrin based canine mitral valve constructs, which can be used as an in vitro platform to study the pathogenesis of MMVD. Prior to three dimensional (3D) construct fabrication, primary canine mitral valve endothelial cells (VECs) and valve interstitial cells (VICs) were isolated, cultured and characterized utilising a variety of techniques. Moreover, preliminary experiments were carried out to optimise the purity of VEC cultures. It is uncertain if canine MMVD is initiated by long term shear stress damage to the valve endothelium or from abnormalities of VICs. To investigate both hypotheses, three types of models were produced using fibrin/based 3D culture techniques: healthy VEC-VIC co-culture (Type 1); healthy VEC-diseased VIC co-culture (Type 2); healthy VEC-VIC co-culture with endothelial damage during culture (Type 3). Histological examination demonstrated partial native tissue-like morphology of the 3D constructs. Results suggest that current static cultured constructs express MMVD markers irrespective of using healthy or diseased VICs. Simple mechanical stimulation was found to regulate VIC activity in the 3D models. Endothelial damage resulting in VIC phenotypic activation (a change typically observed in MMVD), and decreased mechanical tension appeared to be a negative regulator of this effect. Moreover, there appears to be heterogeneity in the activated VIC population. Additionally, distinct advanced glycation end product (AGE) carboxymethyllysine (CML) expression was found in canine MMVD valves, which suggesting this biochemical compound (known to affect long living protein) might be a putative regulator of MMVD pathogenesis. The role of CML in MMVD can be further investigated utilizing current 3D static mitral valve construct model in future studies. Lastly a prototype dynamic tubular construct and a customised bioreactor system were developed. Preliminary data suggest the feasibility of tubular construct fabrication and endothelialisation, which provides foundation for future dynamic conditioning experiments and will allow examination of the role of endothelial shear stress in triggering MMVD. In summary, this project successfully developed fibrin based canine mitral valve constructs. It is believed they are promising models for MMVD research, allowing new insights in understanding MMVD pathogenesis.

Submitted by Fabiana Gonçalves Pinto (benf@ndc.uff.br) on 2016-05-18T20:10:49Z No. of bitstreams: 1 Allana Raphaela dos Santos Cardoso.pdf: 20267087 bytes, checksum: d5ccdc762ece6cf3585e610e83e44191 (MD5) / Made available in DSpace on 2016-05-18T20:10:49Z (GMT). No. of bitstreams: 1 Allana Raphaela dos Santos Cardoso.pdf: 20267087 bytes, checksum: d5ccdc762ece6cf3585e610e83e44191 (MD5) Previous issue date: 2016 / Mestrado Profissional em Enfermagem Assistencial / Objetivos: construir um instrumento para aplicação do processo de enfermagem para pacientes hospitalizados em unidades cardiológicas; treinar os enfermeiros destas unidades para o uso do instrumento e; avaliar a qualidade dos registros antes e após o treinamento por meio do Quality of Diagnosis, Interventions and Outcomes (Q-DIO). Métodos: Trata-se de um estudo quase-experimental que avaliou os registros de enfermagem de prontuários de pacientes de unidades cardiológicas, de um hospital universitário na cidade do Rio de Janeiro/RJ. Foi realizado em duas fases: a elaboração do instrumento para aplicação do processo de enfermagem para os pacientes com distúrbios cardiológicos hospitalizados, baseado na linguagem padronizada NANDA-I, NIC E NOC (NNN) baseada em uma revisão integrativa sobre registros de enfermagem para pacientes com doenças cardiovasculares e na sequência foi realizado um treinamento com enfermeiros das unidades cardiológicas sobre registro de enfermagem e uso do instrumento. O Q-DIO foi aplicado para avaliação da qualidade dos registros antes e após o treinamento. Resultados: O instrumento elaborado possibilitou o registro de enfermagem pautado nos domínios da NANDA-I e a seleção dos diagnósticos, intervenções e resultados foi de acordo com a literatura. O treinamento foi realizado com enfermeiros das unidades cardiológicas e proporcionou uma troca de experiências teórico-práticas positivas. Após o treinamento com os enfermeiros sobre o uso de linguagens padronizadas NNN e o uso do instrumento, o escore total do Q-DIO aumentou no momento pós-intervenção (14,8±5,7vs.29,0±10,5; p=0,003). Conclusão: A qualidade dos registros foi considerada satisfatória após treinamento e utilização do instrumento para aplicação do processo de enfermagem, no entanto, são necessárias mais pesquisas experimentais sobre o processo de enfermagem e sobre a qualidade do registro de enfermagem principalmente referente às intervenções de enfermagem. / Goals: to build an instrument for the application of the nursing process for hospitalized patients in cardiac units; to train nurse of these units for the use o the instrument and; to assess the quality of the records before and after the treatment through the Quality of Diagnosis, Interventions and Outcomes (Q-DIO). Methods: It is a quasi-experimental study that evaluated the nursing records of patients of cardiac units of an academic hospital in the city of Rio de Janeiro/RJ. It was performed in two phases: the elaboration of the instrument for the application of the nursing process for hospitalized patients with cardiac disorders based on a standardized language NANDA-I, NIC E NOC (NNN) based on a integrative revision about the nursing records for patients with cardiac diseases and in the sequence it was performed a training with nurses from cardiac units about the nursing records and the usage of the instrument. The Q-DIO was applied for the evaluation of the quality of the records before and after the training. Outcomes: The elaborated instrument enabled the nursing records based on NANDA-I domains and the diagnosis selection, interventions and results was according to the literature. The training was performed with nurses from cardiac units and provided a positive theoretical-practical exchange of experiences. After the training with the nurses about the use of the NNN standardized language and the use of the instrument, the total score of the Q-DIO increased in the post-intervention moment (14,8±5,7vs.29,0±10,5; p=0,003). Conclusion: The quality of the records was considered satisfactory, after training and the usage of the instrument for the application of the nursing process, however it is necessary to have more experimental research about the nursing process and about the quality of the nursing process mainly for the nursing interventions.

No description available.

HINTERGRUND: Die Typ-D-Persönlichkeit (von distressed personality) etablierte sich in den letzten Jahren als ein Risikofaktor für den Verlauf kardiovaskulärer Erkrankungen. Die bisherigen Studien waren in den Niederlanden oder Belgien durchgeführt worden. Das Ziel der hier vorliegenden Arbeit war eine unabhängige Überprüfung der Ergebnisse an einer Stichprobe deutscher kardiologischer Patienten. Zusätzlich sollte untersucht werden, ob die Typ-D-Persönlichkeit und ihre Dimensionen der negativen Affektivität (NA) und der sozialen Inhibition (SI) über den Untersuchungszeitraum stabil blieben. METHODEN: Hierzu wurden 1040 stationär oder ambulant kardiologisch behandelte Patienten rekrutiert. Mithilfe der Typ-D-Skala (DS14) und der Hospital Anxiety and Depression Scale (HADS) wurden die Merkmale einer Typ-D-Persönlichkeit sowie Depressivität und Ängstlichkeit erhoben. Zusätzlich wurden klinisch relevante Daten, wie z. B. Geschlecht, Alter und kardiale Vorerkrankungen, erfasst. Endpunkt der Studie war die Gesamtmortalität. Mit Cox-Regressionsanalysen wurde das relative Sterblichkeitsrisiko der Probanden ermittelt. ERGEBNISSE: Hinsichtlich der Stabilität von Typ-D, NA und SI ergaben sich über einen Zeitraum von 5,9 Jahren Re-Test Stabilitäten an der unteren Grenze des Erwarteten. Es gab also eine gewisse Stabilität der Typ-D-Persönlichkeit, diese war aber nicht wesentlich höher als beispielsweise die von Angst und Depressivität, und auf Ebene des individuellen Patienten kam es häufig zu Veränderungen. Der Überlebensstatus ließ sich für 977 Studienteilnehmer ermitteln, hiervon waren 172 im Beobachtungszeitraum verstorben. In univariater und multivariater Analyse waren weder Typ-D noch NA oder SI Prädiktionsfaktoren einer höheren Gesamtmortalität. Im Gegensatz zu anderen Studien wies unsere Stichprobe ein heterogenes kardiales Erkrankungsprofil auf. Eine hierdurch bedingte Verschleierung eines Einflusses des Typ-D-Musters konnten wir durch separate Untersuchung der KHK-Patienten ausschließen. SCHLUSSFOLGERUNG: Zusammenfassend lässt sich sagen, dass unsere Studie zu den größten zählt, die bisher zur Evaluation des Einflusses der Typ-D-Persönlichkeit auf die Gesamtmortalität kardiologischer Patienten durch-geführt worden ist. Nach mehr als 5 Jahren Beobachtungszeit, mit 5764 Menschenjahren und 172 beobachteten Todesfällen hat sie suffiziente Ausdruckskraft, relevante Effekte der Typ-D-Persönlichkeit auf die Mortalität aufzudecken. Die klare Abwesenheit dieses Effektes in univariater und multivariater Analyse legt den Schluss nahe, dass die Typ-D-Persönlichkeit und ihre Dimensionen NA und SI bei deutschen kardiologischen Patienten nicht mit einer erhöhten Mortalität assoziiert sind. Die Diskrepanz zwischen unseren Ergebnissen und den Ergebnissen von Denollet und seiner Arbeitsgruppe macht weitere Forschung an anderen Stichproben nötig. Kulturelle Unterschiede in der Verarbeitung negativer Affekte sind als mögliche Ursache unserer abweichenden Ergebnisse zu diskutieren und sollten in zukünftigen Studien weiter untersucht werden.

Este estudo aborda o planeamento dedicado a diminuir os índices de mortalidade materna em cardiopatia e gravidez, a partir da metodologia apresentada pelo serviço do Instituto Dante Pazzanese de Cardiologia, verificando a utilização de equipamentos para o melhor diagnóstico, e do fluxo de atendimento na região do serviço do Sistema Único de Saúde. Foram analisados cinco serviços de atendimento às gestantes portadoras de cardiopatia dentro do Sistema Único de Saúde no Estado de São Paulo. Foram estudados os prontuários de 133 mulheres portadoras de cardiopatia no período gestacional. As cardiopatias encontradas foram classificadas em quatro categorias, as de origem reumática, as de origem genética, as miocardiopatias e no termo \"outras cardiopatias\". As regiões geográficas no Estado de São Paulo integrantes do nosso estudo, foram classificadas em suas políticas quanto a serem favoráveis ou não ao Sistema Único de Saúde, verificando os fatores que impedem o desenvolvimento das ações do Sistema Único de Saúde. Verificamos no prontuário das gestantes o município de procedência, a idade, o número de gestações, a paridade, o número de abortos, o peso e altura, a doença base e as doenças intercorrentes, se foi realizada cirurgia cardíaca, a utilização de equipamentos para diagnósticos, a semana da primeira consulta e a semana do parto, se o local do parto era referência do Sistema Único de Saúde. Para o recém-nascido foi verificado o peso, o comprimento, o sexo e a contagem de Apgar no primeiro e quinto minuto. Os resultados obtidos foram sempre que possivel colocados em tabelas. Foi verificado a necessidade do aconselhamento do planeamento familiar nos serviços visitados. Foi sugerido o número de médicos para atendimento ambulatorial e o número de leitos para o serviço de referência da região, de acordo com o número esperado de gestantes portadoras de cardiopatia. / This study intends to planify the way of diminish the maternal mortality scores in heart disease and pregnancy, using as model the methods in the Instituto Dante Pazzanese de Cardiologia verifying the use of equipments for diagnosis, and the attending flow in the region in the services from the Sistema Único de Saúde (SUS). (Unique health system) Five services for care of cardiac pregnant women of the SUS in the state of São Paulo were analysed. The heart disease diagnosis in these patients were classified in four groups: Rheumatic origen, genetic origen, miocadiopathy and the other heart disease. The regions of our study were classified in favourable or not favourable to the politics of the Sistema Único de Saúde, verifying the factors that block the development of the actions of the SUS. Several informations were obtained from the patients\' file: the district of procedure; the age; the number of gestations; the parity; the number of miscarriages; height and weight; the basic diseases and the intercorrent diseases; the kind of cardiac surgery, if it occurred; the use of diagnostic equipment; the week of gestation in the first appointment; the week of gestation when the delivery occurred; if the place where the delivery occurred was used as reference in the SUS. About the newborn it was observed: the sex; the weight; the height; the Apgar score. The results obtained were distributed in tables, everytime it was possible. It was observed the need of planning parenthood counselling in the visited services. Through the analyses of these informations it was suggested the number of doctors to the ambulatorial care and the number of beds to the reference service in the region according to the expectative of pregnant cardiac women.

Este estudo aborda o planeamento dedicado a diminuir os índices de mortalidade materna em cardiopatia e gravidez, a partir da metodologia apresentada pelo serviço do Instituto Dante Pazzanese de Cardiologia, verificando a utilização de equipamentos para o melhor diagnóstico, e do fluxo de atendimento na região do serviço do Sistema Único de Saúde. Foram analisados cinco serviços de atendimento às gestantes portadoras de cardiopatia dentro do Sistema Único de Saúde no Estado de São Paulo. Foram estudados os prontuários de 133 mulheres portadoras de cardiopatia no período gestacional. As cardiopatias encontradas foram classificadas em quatro categorias, as de origem reumática, as de origem genética, as miocardiopatias e no termo \"outras cardiopatias\". As regiões geográficas no Estado de São Paulo integrantes do nosso estudo, foram classificadas em suas políticas quanto a serem favoráveis ou não ao Sistema Único de Saúde, verificando os fatores que impedem o desenvolvimento das ações do Sistema Único de Saúde. Verificamos no prontuário das gestantes o município de procedência, a idade, o número de gestações, a paridade, o número de abortos, o peso e altura, a doença base e as doenças intercorrentes, se foi realizada cirurgia cardíaca, a utilização de equipamentos para diagnósticos, a semana da primeira consulta e a semana do parto, se o local do parto era referência do Sistema Único de Saúde. Para o recém-nascido foi verificado o peso, o comprimento, o sexo e a contagem de Apgar no primeiro e quinto minuto. Os resultados obtidos foram sempre que possivel colocados em tabelas. Foi verificado a necessidade do aconselhamento do planeamento familiar nos serviços visitados. Foi sugerido o número de médicos para atendimento ambulatorial e o número de leitos para o serviço de referência da região, de acordo com o número esperado de gestantes portadoras de cardiopatia. / This study intends to planify the way of diminish the maternal mortality scores in heart disease and pregnancy, using as model the methods in the Instituto Dante Pazzanese de Cardiologia verifying the use of equipments for diagnosis, and the attending flow in the region in the services from the Sistema Único de Saúde (SUS). (Unique health system) Five services for care of cardiac pregnant women of the SUS in the state of São Paulo were analysed. The heart disease diagnosis in these patients were classified in four groups: Rheumatic origen, genetic origen, miocadiopathy and the other heart disease. The regions of our study were classified in favourable or not favourable to the politics of the Sistema Único de Saúde, verifying the factors that block the development of the actions of the SUS. Several informations were obtained from the patients\' file: the district of procedure; the age; the number of gestations; the parity; the number of miscarriages; height and weight; the basic diseases and the intercorrent diseases; the kind of cardiac surgery, if it occurred; the use of diagnostic equipment; the week of gestation in the first appointment; the week of gestation when the delivery occurred; if the place where the delivery occurred was used as reference in the SUS. About the newborn it was observed: the sex; the weight; the height; the Apgar score. The results obtained were distributed in tables, everytime it was possible. It was observed the need of planning parenthood counselling in the visited services. Through the analyses of these informations it was suggested the number of doctors to the ambulatorial care and the number of beds to the reference service in the region according to the expectative of pregnant cardiac women.