Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro / As células tronco são caracterizadas pela sua capacidade de se diferenciar em várias linhagens de células e exibir um pontente efeito parácrino. O objetivo deste trabalho foi avaliar o efeito da terapia com células da medula óssea (BMCs) na glicose sanguínea, no metabolismo lipídico e remodelamento da parede da aorta em um modelo experimental para aterosclerose. Camundongos C57BL/6 foram alimentados com uma dieta controle (grupo CO) ou uma dieta aterogênica (grupo AT - 60% gordura). Após 16 semanas, o grupo AT foi dividido em quatro sub grupos: grupo AT 14 dias e o grupo AT 21 dias receberam uma injeção de PBS na veia caudal e mortos 14 e 21 dias após respectivamente; grupo AT-BMC 14 dias e AT-BMC 21 dias que receberam uma injeção com BMCs na veia caudal e mortos 14 e 21 dias após, respectivamente. O grupo CO foi sacrificado juntamente com outros grupos. O transplante BMCs reduziu os niveis de glicose, triglicerídeos e colesterol total no sangue. Não houve diferença significativa em relação à massa corporal entre os grupos transplantados e não transplantados, sendo todos diferentes do grupo CO. Não houve diferença significativa na curva glicemica entre os grupos AT 14 dias, AT-BMC 14 dias e AT 21 dias e estes diferentes do grupo CO e do grupo AT-BMC 21 dias. O Qa (1/mm2) foi quantitativamente reduzido no grupo AT 14 dias e AT 21 dias quando comparado ao grupo CO. Este Qa se mostrou elevado no grupo AT-BMC 21 dias quando comparado a todos os grupos. O aumento da expessura da parede da aorta foi observado em todos os grupos aterogênicos, entretanto o aumento da espessura foi significativamente menor no grupo AT-BMC 21 dias em relação ao grupo AT 14 dias e AT 21 dias. A percentagem de fibras elásticas se apresentou significativamente maior no grupo AT 21 dias quando comparado ao CO e AT-BMC 21 dias. Não houve diferença significativa entre o grupo CO e AT-BMC 21 dias. Vacúolos na túnica média, delaminação e o adelgaçamento das lamelas elásticas foram observados nos grupos AT-14 dias e AT-21 dias. O menor número destes foi visualizado no grupo AT-BMC 14 dias e AT-BMC 21 dias. A imunomarcação para alfa actina de músculo liso (α-SMA) e fator de crescimento vascular e endotelial (VEGF) mostrou menor marcação em grupos transplantados com BMCs. A marcação para antígeno nuclear de proliferação celular (PCNA) mostrou-se mais expressiva no grupo AT-BMC 21 dias grupo. Marcação para CD105, CD133 e CD68 foi observada nos grupos AT 14 dias e AT 21 dias. Estas marcações não foram observadas nos grupos AT-BMC 14 dias e AT-BMC 21 dias. Nas eletromicrografias observamos o remodelamento benéfico no grupo AT-BMC14 dias e AT-BMC 21 dias, com a organização estrutural similar ao grupo CO. Vesículas de pinocitose, projeção da célula muscular lisa e a delaminação da lamina elástica interna são observados nos grupos AT 14 dias e AT 21 dias. Célula endotelial preservada, com lamina elástica interna de contorno regular e contínua é observada no grupo CO e nos grupos AT-BMC 14 dias e AT-BMC 21 dias. Como conclusão, os nossos resultados reforçam o conceito de que, em um modelo aterosclerótico utilizando camundongos e dieta aterogênica, a injeção de BMCs melhora os níveis de glicose, metabolismo lipídico e ocasiona um remodelamento benéfico na parede da aorta. / Stem cells are characterized by their ability to differentiate into multiple cell lineages and display the paracrine effect. The aim of this work was to evaluate the effect of therapy with bone marrow cells (BMCs) on blood glucose, lipid metabolism and aortic wall remodeling in mice through the administration of a high fat diet and subsequent BMCs transplantation. C57BL/6 mice were fed a control diet (CO group) or an atherogenic diet (AT group). After 16 weeks, the AT group was divided into four groups: an AT 14 days group and AT 21 days group, that were given an injection of vehicle and sacrificed at 14 and 21 days after, respectively; AT-BMC 14 days group and AT-BMC 21 days group that was given an injection of BMCs and sacrificed at 14 and 21 days after. The CO group was sacrificed along with other groups. The BMCs transplant had reduced blood glucose, triglycerides and total cholesterol. There was no significant difference in relation to body mass between the transplanted groups and non-transplanted groups, with all are different to CO group. There was no significant difference in the glycemic curve between AT 14 days group, AT-BMC 14 days group and AT 21 days group and these are different to CO and the AT-BMC 21 days group. The Qa (1 / mm2) was quantitatively reduced in the AT 14 days group and AT 21 days group when compared to the CO group. This Qa proved high in AT-BMC 21 days BMC compared to all groups. The increased thickness of the aortic wall was observed in all atherogenic groups, but was significantly smaller in group AT-BMC 21 days compared to AT 14 days group and AT 21 days group. The percentage of elastic fibers was significantly higher in the AT 21 days group when compared to the CO and AT-BMC 21 days. There was no significant difference between the CO and AT-BMC 21 days. Vacuoles in the media tunic, delamination and the thinning of the elastic lamellae were observed in AT 14 days group and AT 21 days group. The smallest number of these apresentation were displayed on the AT-BMC 14 days group and and AT-BMC 21 days. The immunostaining for α-SMA and VEGF showed lower in AT-BMC 14 days group and AT-BMC 21 days group. The markup for PCNA appears to be greater in the AT-BMC 21 days group. Marking to CD105, CD133 and CD68 were observed in AT 14 days group and AT 21 days group. These markings were not observed in AT-BMC 14 days group and AT-BMC 21 days group. In electron micrographs observed the beneficial remodeling in AT-BMC 14 day group and AT-BMC 21 days, with the structural organization was similar to the CO group. Vesicles of pinocytosis, projection of smooth muscle cell and delamination of the internal elastic lamina are seen in groups AT 14 days group and AT 21 days group. Endothelial cell preserved, regular and continuous contour in internal elastic lamelae is observed in the CO group, AT-BMC 14 days group and AT-BMC 21 days group. In conclusion, our results support the concept that an atherosclerotic model using mice and atherogenic diet, the injection of BMCs improve glucose, lipid metabolism and causes a beneficial remodeling of the aortic wall.

Made available in DSpace on 2014-06-11T19:31:01Z (GMT). No. of bitstreams: 0 Previous issue date: 2004Bitstream added on 2014-06-13T18:41:27Z : No. of bitstreams: 1 hueb_jc_dr_botfm.pdf: 402586 bytes, checksum: 0363aade5dace29841c7485277d2b0f8 (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Placa de aterosclerose em aorta torácica é uma importante causa de acidente vascular cerebral (AVC) e ataque isquêmico transitório (AIT). Sua gênese estaria relacionada com migração, para a circulação cerebral, de trombos e cristais de colesterol que se desprenderiam de placas complexas, localizadas na aorta torácica proximal. Existem várias semelhanças entre a fisiopatologia do desenvolvimento da placa de aterosclerose e a remodelação miocárdica. Por causa disso, formulou-se a hipótese de que a avaliação de pacientes com AVC e AIT, por meio do ecocardiograma transtorácico ((ETT), pode identificar características associadas com risco aumentado de placa de aterosclerose em aorta. Os objetivos desse estudo foram: 1) avaliar a incidência de placa de aterosclerose em aorta torácica de pacientes com história de AVC e AIT prévios, por meio do ecocardiograma transesofágico (ETE); 2) avaliar se existe associação entre a presença dessas placas e sinais de remodelação ventricular, observados por meio do ETT; e, finalmente, 3) analisar os níveis séricos de proteína C reativa de alta sensibilidade (PCRas), nesses pacientes... / Atherosclerosis plaque in the thoracic aorta is an important cause of acute cerebrovascular events. It would be caused by migration of thrombi and cholesterol cristals released from complex plaques, located at the proximalis thoracic aorta, to the cerebral circulation. Because there are several similarities between the physiopathology of atherosclerosis plaque development and myocardial remodeling. We hypothesized that patients with cerebrovascular events, and atherosclerosis plaque have cardiac morpho-functional alterations. The objectives of the present study were: 1) to evaluate the incidence of thoracic aorta artherosclerosis plaques in patients with a previous cerebrovascular events history, by transesophageal echocardiogram (TEE); 2) to evaluate if there is an association between the presence of plaques and signs of ventricular remodeling, observed by means of transthoracic echocardiogram; and, 3) to analyze the high sensitivity C-reactive protein (hs-CRP) seric levels, in those patients. One hundred and sixteen patients (79 male) with a previous... (Complete abstract click electronic address below)

Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências da Saúde. Programa de Pós-Graduação em Ciências Médicas. / Made available in DSpace on 2013-07-16T03:50:53Z (GMT). No. of bitstreams: 1 310110.pdf: 339089 bytes, checksum: 73dbf9bdb335a97c9e58214037a9667e (MD5) / Justificativa: O objetivo do tratamento endovascular do aneurisma de aorta abdominal é a exclusão do saco aneurismático da circulação sistêmica. Para acompanhar a eficácia do tratamento é necessária a realização de angiotomografias seriadas. A monitorização continuada da pressão poderia diagnosticar precocemente casos em que esteja ocorrendo falha desse tratamento, auxiliando ou substituindo a tomografia. Objetivo: Avaliar a eficácia em médio prazo da medida de pressão através de sensor sem fio implantado no saco aneurismático após tratamento endovascular de aneurisma de aorta abdominal (AAA). Desenho do Estudo: Quarenta pacientes submetidos a tratamento endovascular de aneurisma de aorta abdominal receberam implante de sensor sem fio para monitorização em médio prazo da pressão intra-saco. Os dados foram analisados no primeiro, sexto, décimo segundo meses e anualmente. A cada análise, uma angiotomografia informava o diâmetro do aneurisma, presença e tipo de vazamento. A pressão arterial sistêmica assim como todos os dados pressóricos obtidos através do sensor foram coletados. Resultados: No seguimento, dos 40 sensores implantados apenas em dois o sinal não pode ser detectado. A pressão de pulso obtida apresentou boa sensibilidade em afastar a presença de vazamento quando inferior a 25mmHg no primeiro ano. Após esse período, o Índice de Endotensão mostra-se como a variável que mais se aproxima dos dados tomográficos. Na presença de vazamantos tipo I ou III, o sensor é capaz de identificar sucesso ou falha após a correção do vazamento. Até o segundo ano de seguimento, resultados apresentados pelo sensor são concordantes com dados tomográficos, a partir daí, perdem acurácia. Conclusão: Na amostra estudada não foi possível obter sensibilidade suficiente para substituir a realização da tomografia no acompanhamento dos AAA tratados por técnica endovascular. Um maior número de pacientes é necessário para estabelecer o verdadeiro papel da monitorização pressórica sem fio no seguimento do tratamento endovascular do aneurisma de aorta abdominal. / Racional: The objective of endovascular treatment of an abdo-minal aortic aneurysm is to exclude the aneurysm sac from systemic circulation. In order to assess treatment effectiveness it is necessary to perform serial computed tomography (CT). Continued pressure moni-toring could provide an early diagnosis of cases in which this treatment is failing, helping or replacing CT. Objective: Evaluation of medium-term effectiveness of pressure measurement using a wireless sensor implanted in the aneurysm sac after endovascular treatment of abdominal aortic aneurysm. Method: Forty patients undergoing endovascular treatment for abdominal aortic aneurysm had a wireless sensor implanted for medium-term monitoring of intrasac pressure. The data were analyzed in the first, sixth and twelfth month and annually. At each analysis, a CT scan in-formed the aneurysm diameter, presence and risk of endoleaks. System-ic arterial pressure was collected, as well as all pressure data obtained through the sensor. Results: Of the 40 sensors implanted, the signal could not be de-tected only in two. The pulse pressure obtained presented good sensitivi-ty to rule out the presence of leakage when it was less than 25mmHg during the first year. After this period, the Endotension Index is the variable that comes closest to the CT scan data. With type I or III endo-leaks, the sensor can identify success or failure after endoleak repair. Until the second year of follow up, the results presented by the sensor agree with CT data, and then become less accurate. Conclusions: In the sample studied sufficient sensitivity could not be achieved to replace the CT when following AAA treated by the en-dovascular technique. A larger number of patients is needed to deter-mine the true role of wireless pressure monitoring when following en-dovascular treatment of abdominal aortic aneurysm.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro / As células tronco são caracterizadas pela sua capacidade de se diferenciar em várias linhagens de células e exibir um pontente efeito parácrino. O objetivo deste trabalho foi avaliar o efeito da terapia com células da medula óssea (BMCs) na glicose sanguínea, no metabolismo lipídico e remodelamento da parede da aorta em um modelo experimental para aterosclerose. Camundongos C57BL/6 foram alimentados com uma dieta controle (grupo CO) ou uma dieta aterogênica (grupo AT - 60% gordura). Após 16 semanas, o grupo AT foi dividido em quatro sub grupos: grupo AT 14 dias e o grupo AT 21 dias receberam uma injeção de PBS na veia caudal e mortos 14 e 21 dias após respectivamente; grupo AT-BMC 14 dias e AT-BMC 21 dias que receberam uma injeção com BMCs na veia caudal e mortos 14 e 21 dias após, respectivamente. O grupo CO foi sacrificado juntamente com outros grupos. O transplante BMCs reduziu os niveis de glicose, triglicerídeos e colesterol total no sangue. Não houve diferença significativa em relação à massa corporal entre os grupos transplantados e não transplantados, sendo todos diferentes do grupo CO. Não houve diferença significativa na curva glicemica entre os grupos AT 14 dias, AT-BMC 14 dias e AT 21 dias e estes diferentes do grupo CO e do grupo AT-BMC 21 dias. O Qa (1/mm2) foi quantitativamente reduzido no grupo AT 14 dias e AT 21 dias quando comparado ao grupo CO. Este Qa se mostrou elevado no grupo AT-BMC 21 dias quando comparado a todos os grupos. O aumento da expessura da parede da aorta foi observado em todos os grupos aterogênicos, entretanto o aumento da espessura foi significativamente menor no grupo AT-BMC 21 dias em relação ao grupo AT 14 dias e AT 21 dias. A percentagem de fibras elásticas se apresentou significativamente maior no grupo AT 21 dias quando comparado ao CO e AT-BMC 21 dias. Não houve diferença significativa entre o grupo CO e AT-BMC 21 dias. Vacúolos na túnica média, delaminação e o adelgaçamento das lamelas elásticas foram observados nos grupos AT-14 dias e AT-21 dias. O menor número destes foi visualizado no grupo AT-BMC 14 dias e AT-BMC 21 dias. A imunomarcação para alfa actina de músculo liso (α-SMA) e fator de crescimento vascular e endotelial (VEGF) mostrou menor marcação em grupos transplantados com BMCs. A marcação para antígeno nuclear de proliferação celular (PCNA) mostrou-se mais expressiva no grupo AT-BMC 21 dias grupo. Marcação para CD105, CD133 e CD68 foi observada nos grupos AT 14 dias e AT 21 dias. Estas marcações não foram observadas nos grupos AT-BMC 14 dias e AT-BMC 21 dias. Nas eletromicrografias observamos o remodelamento benéfico no grupo AT-BMC14 dias e AT-BMC 21 dias, com a organização estrutural similar ao grupo CO. Vesículas de pinocitose, projeção da célula muscular lisa e a delaminação da lamina elástica interna são observados nos grupos AT 14 dias e AT 21 dias. Célula endotelial preservada, com lamina elástica interna de contorno regular e contínua é observada no grupo CO e nos grupos AT-BMC 14 dias e AT-BMC 21 dias. Como conclusão, os nossos resultados reforçam o conceito de que, em um modelo aterosclerótico utilizando camundongos e dieta aterogênica, a injeção de BMCs melhora os níveis de glicose, metabolismo lipídico e ocasiona um remodelamento benéfico na parede da aorta. / Stem cells are characterized by their ability to differentiate into multiple cell lineages and display the paracrine effect. The aim of this work was to evaluate the effect of therapy with bone marrow cells (BMCs) on blood glucose, lipid metabolism and aortic wall remodeling in mice through the administration of a high fat diet and subsequent BMCs transplantation. C57BL/6 mice were fed a control diet (CO group) or an atherogenic diet (AT group). After 16 weeks, the AT group was divided into four groups: an AT 14 days group and AT 21 days group, that were given an injection of vehicle and sacrificed at 14 and 21 days after, respectively; AT-BMC 14 days group and AT-BMC 21 days group that was given an injection of BMCs and sacrificed at 14 and 21 days after. The CO group was sacrificed along with other groups. The BMCs transplant had reduced blood glucose, triglycerides and total cholesterol. There was no significant difference in relation to body mass between the transplanted groups and non-transplanted groups, with all are different to CO group. There was no significant difference in the glycemic curve between AT 14 days group, AT-BMC 14 days group and AT 21 days group and these are different to CO and the AT-BMC 21 days group. The Qa (1 / mm2) was quantitatively reduced in the AT 14 days group and AT 21 days group when compared to the CO group. This Qa proved high in AT-BMC 21 days BMC compared to all groups. The increased thickness of the aortic wall was observed in all atherogenic groups, but was significantly smaller in group AT-BMC 21 days compared to AT 14 days group and AT 21 days group. The percentage of elastic fibers was significantly higher in the AT 21 days group when compared to the CO and AT-BMC 21 days. There was no significant difference between the CO and AT-BMC 21 days. Vacuoles in the media tunic, delamination and the thinning of the elastic lamellae were observed in AT 14 days group and AT 21 days group. The smallest number of these apresentation were displayed on the AT-BMC 14 days group and and AT-BMC 21 days. The immunostaining for α-SMA and VEGF showed lower in AT-BMC 14 days group and AT-BMC 21 days group. The markup for PCNA appears to be greater in the AT-BMC 21 days group. Marking to CD105, CD133 and CD68 were observed in AT 14 days group and AT 21 days group. These markings were not observed in AT-BMC 14 days group and AT-BMC 21 days group. In electron micrographs observed the beneficial remodeling in AT-BMC 14 day group and AT-BMC 21 days, with the structural organization was similar to the CO group. Vesicles of pinocytosis, projection of smooth muscle cell and delamination of the internal elastic lamina are seen in groups AT 14 days group and AT 21 days group. Endothelial cell preserved, regular and continuous contour in internal elastic lamelae is observed in the CO group, AT-BMC 14 days group and AT-BMC 21 days group. In conclusion, our results support the concept that an atherosclerotic model using mice and atherogenic diet, the injection of BMCs improve glucose, lipid metabolism and causes a beneficial remodeling of the aortic wall.

Thoracic endovascular aortic repair (TEVAR) is now the treatment of choice for most diseases of the thoracic aorta. Current evidence and guidelines for practice are based on pooled analysis of data that are of variable quality. Questions remain about the applicability of TEVAR to different pathologies, peri-procedural neurological complications, the subsequent durability of the procedure and mid-term survival of patients. Methods and Results A systematic review of the literature was performed to describe the incidence of peri-operative and mid-term adverse events following TEVAR. For the main investigation, data from five phase IV trials was combined with that from St George's Vascular Institute to form a composite dataset of 1010 patients that underwent TEVAR from 2002-2010. A high rate of mid-term all cause mortality was observed in patients treated for thoracic aortic aneurysm, with less than 60% of those treated living beyond 5 years. Factors predicting neurological complications were determined using logistic regression modelling. Coverage of the left subclavian artery was the most important predictor of post-operative stroke, specifically in posterior vascular territories. Patients undergoing elective repair of thoracic aortic aneurysms were stratified into those at high, intermediate and low risk of a death wi!hin five years using regression models based on pre-operative factors. Those at high and low risk of aortic re-intervention were similarly identified. The models were validated externally using a dataset obtained from the United States. Conclusions Post-operative outcomes following TEVAR are partly dependent on presenting pathology, especially with regards to mid-term all-cause death. Coverage of the left subclavian artery is one of the few potentailly modifiable risk factors for stroke. Patients can risk-stratified according to the risk of midterm all cause death following TEVAR, and careful consideration should be given before treating patients who may not benefit in terms of overall life expectency.

No description available.

Although surgical and transcatheter interventions have significantly improved survival of patients with coarctation of the aorta (CoA) and interrupted aortic arch (IAA), long-term complications including left ventricular (LV) abnormalities and systemic arterial dysfunction remain issues of concern despite successful repair. While new indices of myocardial deformation that reflect diastolic and systolic function in terms of strain, strain rate, and torsion as detected by speckle tracking echocardiography have shown promise in the assessment of LV, left atrial (LA), and right ventricular (RV) mechanics, the understanding of ventricular myocardial deformation after repair of CoA is limited. In this thesis, studies were undertaken to test the hypotheses that LV, LA, and RV myocardial deformation is altered and related to structural and functional arterial alterations in adolescents and young adults late after successful intervention of CoA and IAA, and to explore the LV contractile reserve noninvasively by examining the force-frequency relationship (FFR) in these patients. The LV, LA, and RV mechanics were evaluated with tissue Doppler and speckle tracking echocardiography, while carotid arterial structure and function were determined by radiofrequency-based echocardiographic imaging and oscillometry techniques. Supine bicycle stress exercise testing was used to evaluate the FFR by tracking the changes in LV contractility with increase in heart rate. Patients after CoA and IAA repair had significantly greater carotid arterial stiffness and intima-media thickness when compared with controls. Furthermore, mitral annular systolic and diastolic velocities, LV longitudinal and radial strain and early diastolic strain rates, peak torsion and untwisting velocity, and LA peak positive and total strain, and LA strain rates at ventricular systole, early diastole, and atrial contraction were significantly lower in patients than controls. Increased arterial stiffness and intima-media thickness was associated with worse LV myocardial deformation, while LA total strain and LA strain rate at ventricular early diastole were associated with diastolic annular velocities and strain rates. Multivariate analysis further revealed arterial stiffness as an independent determinant of LA total strain. With regard to dynamic assessment of LV contractile reserve, at submaximal exercise, the systemic blood pressures were significantly greater in patients than controls, while mitral annular systolic and early diastolic velocities remained significantly reduced. The increase in LV myocardial isovolumic acceleration, a relative load independent index of contractility, with increase in heart rate during exercise stress was significantly reduced in patients compared with controls. Flattening of FFR in patients reflected impaired LV contractile reserve, which was found to be associated negatively with increment in systemic blood pressure during exercise. For RV mechanics, patients with CoA repaired exhibited significantly lower tricuspid annular systolic and early diastolic velocities, global RV systolic longitudinal strain, and strain rate during systole, early and late diastole, compared to controls. Impairment of RV deformation was further related to increased LV mass and RV thickness. In conclusion, these findings suggest arterial dysfunction, impaired LV, RV, and LA mechanics, and reduced LV contractile reserve, in patients late after CoA and IAA repair even in the absence of residual aortic narrowing and implicate abnormal arterial-LV-LA and LV-RV interactions. / published_or_final_version / Paediatrics and Adolescent Medicine / Master / Master of Philosophy

No description available.

Proefschrift Universiteit van Amsterdam. / Met lit. opg. - Met samenvatting in het Nederlands.

Thesis (M.S.)--University of Iowa, 2009. / Thesis supervisor: Milan Sonka. Includes bibliographical references (leaves 48-49).