No description available.

No description available.

Branchial arches (BAs) are a series of transient structures that develop on the ventro-lateral surface of the head in vertebrate embryos. BAs initially appear as a series of similar segments; as development proceeds each BA will contribute to different structures. Here, it was investigated the transcriptional mechanisms that instruct the different fates of the BAs in development. Initially, each BA contains a blood vessel, known as aortic arch (AA) artery, that connects the dorsal aorta with the heart. Remodelling of the AAs is crucial to form the adult heart circulation. This process leads to regression of the anterior AAs, running though the first and second BAs (BA1 and BA2), and persistence of the AAs contained in more posterior BAs (PBA). To identify the mechanisms that control remodelling of the AAs, we compared the transcriptomes and epigenomic landscapes of different BAs. Using RNA-seq and H3K27Ac ChIP-seq, we uncovered the activation of a vascular smooth muscle cell (VSMC) differentiation transcriptional program exclusively in the PBAs (and not in BA1/BA2). In support of this finding, we show that VSMC differentiation occurs specifically in the PBAs, but not BA1-2 in mouse embryonic development. Despite the absence of VSMC differentiation in developing BA1-2, cells harvested from these tissues reveal a spontaneous tendency to differentiate towards VSMC fate when grown in vitro, and activate several VSMC-specific genes (Myocd, Acta2, Tagln, Jag1). Together, our results suggest that forming VSMCs is a key process for the persistence of AAs. We also showed that cells derived from all BAs have the potential to differentiate to VSMCs in vitro. However, only cells in the PBAs differentiate to VSMCs in vivo, resulting in the maintenance of posterior AAs. In this study, we also uncovered a novel transcriptional principle that specifies the fate of BA2. Using ChIP-seq, we found that binding of Meis transcription factors establish a ground pattern in the BAs. Hoxa2, which specifies BA2 identity, selects a subset of Meis-bound sites. Meis binding is strongly increased at these sites, which coincide with active enhancers, linked to genes highly expressed in the BA2 and regulated by Hoxa2. Thus, Hoxa2 modifies a ground state binding of Meis to instruct segment-specific transcriptional programs.

Orientador: Maria Rita Pacheco / Banca: Márcia Rita Fernandes Machado / Banca: Lucia Helena Vasques / Resumo: Aterosclerose é um condição inflamatória fibro-proliferativa crônica associada à produção de espécies oxidantes. O composto fenólico resveratrol encontrado principalmente na uva e no vinho tinto, parece ter atividades cardioprotetoras previnindo a oxidação de lipoproteínas de baixa densidade. Neste estudo investigou-se o efeito do resveratrol na prevenção da ateromatose induzida por meio de estudos morfológicos e morfométricos do arco aórtico, bem como observação do perfil bioquímico sérico de HDL, LDL, triglicerídeos e colesterol total. Para tanto, foram utilizados 20 coelhos divididos em quatro grupos os quais receberam as seguintes dietas durante 60 dias: grupo controle (CT) ração normal; grupo resveratrol (R) raçao normal e resveratrol na dose de 3 mg/Kg/dia; grupo colesterol (CL) ração acrescida de 1,5% de colesterol; grupo (CR) tratado com ração acrescida de 1,5% de colesterol e administração simultânea de resveratrol na dose de 3mg/Kg/dia. Na análise morfologica os animais do grupo CT e R não apresentaram alterações nas túnicas íntima, média e adventícia. Os animais do grupo CL apresentaram lesões ateroscleróticas com espessamento da íntima e invasão da média. Os animais do grupo CR também apresentaram lesões invadindo a íntima e média porém estas encontravam-se mais organizadas. O estudo morfométrico revelou maior espessamento da íntima no grupo CL, na camada média não foi observado diferença entre os grupos CL e CR. A avaliação do perfil lipídico dos animais dos grupos CL e CR revelou valores aumentados porém sem diferença entre estes grupos. Houve diferença quando comparados com os grupos que receberam uma dieta normal...(Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Atherosclerosis is a chronic fibro proliferative inflammatory disease associate to the production of reactive oxygen species. Resveratrol, a phenolic compound present in red wine and grape seems to prevent cardiovascular diseases by protecting low density lipoprotein from oxidation. The present study tested wheter resveratrol would provide any benefit in the prevention of induced atheroma lesions through morphologic, morphometric studies in the aortic arch and HDL, LDL, total cholesterol and triglyceride lipid levels. A total of 20 rabbits were divided into 4 groups during 60 days: group CT was given normal diet, group R normal diet with resveratrol at a dose of 3 mg/Kg/day, group CL normal diet supplemented with 1,5% cholesterol, group CR normal diet supplemented with 1,5% cholesterol with resveratrol at a dose of 3 mg/Kg/day. Morphologic analysis of the rabbit group CT and R didn't show lesion in intima, media and adventitia tunicas in the aortic arch. Rabbits fed with a hypercholesterolemic diet show atherosclerotic lesions with thickness of intima and invasion of the media. Severity of atherosclerosis lesions was significantly reduced in group CR and lesions were more organized, and media was also affected. Morphometry study revealed that the intima of aortic arch in CL animals was thickner than CR animals. The media didn't show difference between CL and CR groups. Lipid measurements of hypercholesterolemic rabbits showed a significant increase in serum levels but there weren't differences between CL and CR group, there were differences when compared to those fed a regular diet...(Complete abstract, click electronic access below) / Mestre

Made available in DSpace on 2014-06-11T19:27:57Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-02-18Bitstream added on 2014-06-13T19:57:06Z : No. of bitstreams: 1 castro_m_me_jabo.pdf: 467319 bytes, checksum: 75c102107c67aefa122635ff9a85a085 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Aterosclerose é um condição inflamatória fibro-proliferativa crônica associada à produção de espécies oxidantes. O composto fenólico resveratrol encontrado principalmente na uva e no vinho tinto, parece ter atividades cardioprotetoras previnindo a oxidação de lipoproteínas de baixa densidade. Neste estudo investigou-se o efeito do resveratrol na prevenção da ateromatose induzida por meio de estudos morfológicos e morfométricos do arco aórtico, bem como observação do perfil bioquímico sérico de HDL, LDL, triglicerídeos e colesterol total. Para tanto, foram utilizados 20 coelhos divididos em quatro grupos os quais receberam as seguintes dietas durante 60 dias: grupo controle (CT) ração normal; grupo resveratrol (R) raçao normal e resveratrol na dose de 3 mg/Kg/dia; grupo colesterol (CL) ração acrescida de 1,5% de colesterol; grupo (CR) tratado com ração acrescida de 1,5% de colesterol e administração simultânea de resveratrol na dose de 3mg/Kg/dia. Na análise morfologica os animais do grupo CT e R não apresentaram alterações nas túnicas íntima, média e adventícia. Os animais do grupo CL apresentaram lesões ateroscleróticas com espessamento da íntima e invasão da média. Os animais do grupo CR também apresentaram lesões invadindo a íntima e média porém estas encontravam-se mais organizadas. O estudo morfométrico revelou maior espessamento da íntima no grupo CL, na camada média não foi observado diferença entre os grupos CL e CR. A avaliação do perfil lipídico dos animais dos grupos CL e CR revelou valores aumentados porém sem diferença entre estes grupos. Houve diferença quando comparados com os grupos que receberam uma dieta normal... / Atherosclerosis is a chronic fibro proliferative inflammatory disease associate to the production of reactive oxygen species. Resveratrol, a phenolic compound present in red wine and grape seems to prevent cardiovascular diseases by protecting low density lipoprotein from oxidation. The present study tested wheter resveratrol would provide any benefit in the prevention of induced atheroma lesions through morphologic, morphometric studies in the aortic arch and HDL, LDL, total cholesterol and triglyceride lipid levels. A total of 20 rabbits were divided into 4 groups during 60 days: group CT was given normal diet, group R normal diet with resveratrol at a dose of 3 mg/Kg/day, group CL normal diet supplemented with 1,5% cholesterol, group CR normal diet supplemented with 1,5% cholesterol with resveratrol at a dose of 3 mg/Kg/day. Morphologic analysis of the rabbit group CT and R didn’t show lesion in intima, media and adventitia tunicas in the aortic arch. Rabbits fed with a hypercholesterolemic diet show atherosclerotic lesions with thickness of intima and invasion of the media. Severity of atherosclerosis lesions was significantly reduced in group CR and lesions were more organized, and media was also affected. Morphometry study revealed that the intima of aortic arch in CL animals was thickner than CR animals. The media didn’t show difference between CL and CR groups. Lipid measurements of hypercholesterolemic rabbits showed a significant increase in serum levels but there weren’t differences between CL and CR group, there were differences when compared to those fed a regular diet...(Complete abstract, click electronic access below)

Made available in DSpace on 2014-06-11T19:23:46Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-07-23Bitstream added on 2014-06-13T18:51:20Z : No. of bitstreams: 1 castro_kf_me_jabo.pdf: 1173046 bytes, checksum: 3f548cfd5539d25d90bbd19c032374f5 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A aterosclerose é uma doença multifatorial, lenta e progressiva e a hiperlipidemia um dos fatores potenciais no desenvolvimento de doenças cardíacas ateroscleróticas. As vantagens da indução das dislipidemias experimentais são a produção de lesões ateromatosas em curto espaço de tempo; adequado controle dietético e fatores ambientais; a possibilidade de estudos sobre a reversibilidade de lesões ateroscleróticas e ensaios pré clínicos de substâncias hipolipidêmicas. Este estudo visou avaliar a capacidade do surfactante na indução aterogênica na região do arco aórtico de ratos por meio de estudos morfológico e morfométrico das túnicas íntima, média e adventícia da aorta, bem como analisar o perfil lipídico sérico. Foram utilizados 28 ratos Wistar, machos, albinos, adultos e hígidos. Estes foram distribuídos em quatro grupos experimentais formados por sete animais cada, a saber: Grupo I – (controle); Grupo II – tratado com tyloxapol, na dose de 500 mg/Kg de peso corporal, via intraperitoneal a cada 48 horas, durante duas semanas; Grupo III – tratado com tyloxapol na dose de 500 mg/Kg de peso corporal, via intraperitoneal a cada 48 horas, durante três semanas; Grupo IV – tratado com tyloxapol na dose de 500 mg/Kg de peso corporal, via intraperitoneal a cada 48 horas, durante quatro semanas. A análise morfológica do arco aórtico dos animais dos grupos II, III e IV evidenciou características histológicas semelhantes às do grupo I nas túnicas íntima, média e adventícia. No estudo morfométrico, os valores da espessura, em μm, da túnica íntima indicaram que o grupo III diferiu significativamente dos grupos I, II e IV. Os valores da espessura, em μm, encontrados para a túnica média e adventícia revelaram que não houve diferença significativa entre os grupos I, II, III e IV. Na avaliação do perfil lipídico os valores de colesterol total... / Atherosclerosis is a multifactorial, progressive and slow disease, and hyperlipidaemia is one of the potential factors in the development of atherosclerotic cardiac diseases. The experimental dyslipidaemia carrying out advantages are the production of atheromatous lesions in a short period of time, an adequate dietetic control and environmental factors, the possibility of studies concerning reversibility of atherosclerotic lesions, and pre-clinic experiments with hypolipidaemic substances. This study aims at evaluating tyloxapol ability in atherogenic inducing, in the rats’ aortic arch region, through morphologic morphometric studies, in intima, media and adventitia tunicas of the aortic arch, as well as analyzing serum lipid levels. Twenty-eight healthy Wistar adults’ albino male rats, weighing an average of 200 g were utilized. They were distributed into four experimental groups with seven animals each, as follows: Group I – (control); Group II – treated with tyloxapol at a dose of 500mg/Kg of body weight, through intraperitoneal via each 48 hours, for two weeks; Group III - treated with tyloxapol at a dose of 500mg/Kg of body weight, through intraperitoneal via each 48 hours, for three weeks; Group IV - treated with tyloxapol at a dose of 500mg/Kg of body weight, through intraperitoneal via each 48 hours, for four weeks. Morphological analysis of the aortic arch of the animals from groups II, III and IV, showed similar histological characteristics to group I at intima, media and adventitia tunicas. The intima tunica values at the morphometric study indicated that group III has significant differed from groups I, II and IV. The media and adventitia tunicas values revealed that there were no significant differences between groups I, II, III, and IV. As lipid profile evaluation is concerned, the values of total cholesterol, triglycerides and HDL have indicated... (Complete abstract click electronic access below)

Previously, we have shown that chronic intermittent hypoxia (CIH) impairs baroreflex control of heart rate and augments aortic baroreceptor afferent function. In the present study, we examined whether CIH induces structural changes of aortic afferent axons and terminals. Young-adult Fischer 344 (F344, 4 months old) rats were exposed to room air (RA) or CIH for 35-45 days. After 14-24 days of exposure, they received tracer DiI injection into the left nodose ganglion to anterogradely label vagal afferent nerves. After surgery, animals were returned to their cages to continue RA or CIH exposure. Twenty-one days after DiI injection, the animals were sacrificed and the aortic arch was examined using confocal microscopy. In both RA and CIH rats, we found that DiI-labeled vagal afferent axons entered the wall of the aortic arch, then fanned out and branched into large receptive fields with numerous terminals (flower-sprays, end-nets and free endings). Vagal afferent axons projected much more to the anterior wall than to the posterior wall. In general, the flower-sprays, end-nets and free endings were widely and similarly distributed in the aortic arch of both groups. However, several salient differences between RA and CIH rats were found. Compared to RA control, CIH rats appeared to have larger vagal afferent receptive fields. The CIH rats had many abnormal flower-sprays, end-nets, and free endings which were intermingled and diffused into "bush-like" structures. However, the total number of flower-sprays was comparable (P>0.05). Since there was a large variance of the size of flower-sprays, we only sampled the 10 largest flower-sprays from each animal. CIH substantially increased the size of large flower-sprays (P<0.01). Numerous free endings with enlarged varicosities were identified, resembling axonal sprouting structures. Taken together, our data indicate that CIH induces significant remodeling of afferent terminal structures in the aortic arch of F344 rats. We suggest that such an enlargement of vagal afferent terminals may contribute to altered aortic baroreceptor function following CIH.

No description available.

Physical bench top experiments are performed to validate and complement ongoing computational fluid dynamics (CFD) analyses of ventricular assist device (VAD) circulation. VADs are used in patients whose hearts do not function to their maximum potential due advanced stages of heart disease and, consequently, are unable to adequately supply blood to the systemic circulation. VADs are commonly utilized as a bridge-to-transplantation, meaning that they are implanted in patients while waiting for a heart transplant. In such cases of long term utilization of VADs, it has been reported in the literatures that thrombo-embolic cerebral events occur in 14-47% of patients over the period of 6 to 12 months. This is a result of thrombus forming despite the use of anticoagulants and advances in VAD design. Accepting current rates of thrombo-embolisms, the main objective of the project is to identify and propose an optimal surgical cannula implantation orientation aimed at reducing the rate of thrombi reaching the carotid and vertebral arteries and thus reduce the morbidity and mortality rate associated with the long term use of VADs to patients suffering from advanced heart failure. The main focus of the experiment is on the physical aspect using a synthetic anatomically correct model constructed by rapid prototyping of the human aortic arch and surrounding vessels. Three VAD cannula implantation configurations are studied with and without bypass to the left carotid artery or to the Innominate artery with ligation of the branch vessel at its root. A mixture of water and glycerin serves to match blood viscosity measured with a rotating cone-plate viscometer. The Reynolds number in the ascending aorta is matched in the flow model. A closed loop mock circulatory system is then realized. In order to match the Reynolds number in the ascending aorta and LVAD cannula with that of the CFD model, a volumetric flow rate of 2.7 liters per minute is supplied through the synthetic VAD cannula and 0.9 liter per minute is supplied to the ascending aorta. Flow rates are measured using rotary flow meters and a pressure sensor is used to ensure a mean operating pressure of 100 mmHg is maintained. Synthetic acrylic blood iv clots are injected at the inlet of the VAD cannula and they are captured and counted at the vertebral and carotid arteries. The sizes of the thrombi simulated are 2, 3.5 and 5 mm which are typical of the range of diameters encountered in practice. Nearly 300 particles are released over 5 separate runs for each diameter, and overall embolization rates as well as individual embolization rates are evaluated along with associated confidence levels. The experimental results show consistency between CFD and experiment. Means comparison of thromboembolization rates predicted by CFD and bench-top results using a Z-score statistic with a 95% confidence level results in 22 of 24 cases being statistically equal. This study provides confidence in the predictive capabilities of the bench-top model as a methodology that can be utilized in upcoming studies utilizing patient-specific aortic bed model.

Resumo: A aterosclerose é uma doença multifatorial, lenta e progressiva e a hiperlipidemia um dos fatores potenciais no desenvolvimento de doenças cardíacas ateroscleróticas. As vantagens da indução das dislipidemias experimentais são a produção de lesões ateromatosas em curto espaço de tempo; adequado controle dietético e fatores ambientais; a possibilidade de estudos sobre a reversibilidade de lesões ateroscleróticas e ensaios pré clínicos de substâncias hipolipidêmicas. Este estudo visou avaliar a capacidade do surfactante na indução aterogênica na região do arco aórtico de ratos por meio de estudos morfológico e morfométrico das túnicas íntima, média e adventícia da aorta, bem como analisar o perfil lipídico sérico. Foram utilizados 28 ratos Wistar, machos, albinos, adultos e hígidos. Estes foram distribuídos em quatro grupos experimentais formados por sete animais cada, a saber: Grupo I - (controle); Grupo II - tratado com tyloxapol, na dose de 500 mg/Kg de peso corporal, via intraperitoneal a cada 48 horas, durante duas semanas; Grupo III - tratado com tyloxapol na dose de 500 mg/Kg de peso corporal, via intraperitoneal a cada 48 horas, durante três semanas; Grupo IV - tratado com tyloxapol na dose de 500 mg/Kg de peso corporal, via intraperitoneal a cada 48 horas, durante quatro semanas. A análise morfológica do arco aórtico dos animais dos grupos II, III e IV evidenciou características histológicas semelhantes às do grupo I nas túnicas íntima, média e adventícia. No estudo morfométrico, os valores da espessura, em μm, da túnica íntima indicaram que o grupo III diferiu significativamente dos grupos I, II e IV. Os valores da espessura, em μm, encontrados para a túnica média e adventícia revelaram que não houve diferença significativa entre os grupos I, II, III e IV. Na avaliação do perfil lipídico os valores de colesterol total... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Atherosclerosis is a multifactorial, progressive and slow disease, and hyperlipidaemia is one of the potential factors in the development of atherosclerotic cardiac diseases. The experimental dyslipidaemia carrying out advantages are the production of atheromatous lesions in a short period of time, an adequate dietetic control and environmental factors, the possibility of studies concerning reversibility of atherosclerotic lesions, and pre-clinic experiments with hypolipidaemic substances. This study aims at evaluating tyloxapol ability in atherogenic inducing, in the rats' aortic arch region, through morphologic morphometric studies, in intima, media and adventitia tunicas of the aortic arch, as well as analyzing serum lipid levels. Twenty-eight healthy Wistar adults' albino male rats, weighing an average of 200 g were utilized. They were distributed into four experimental groups with seven animals each, as follows: Group I - (control); Group II - treated with tyloxapol at a dose of 500mg/Kg of body weight, through intraperitoneal via each 48 hours, for two weeks; Group III - treated with tyloxapol at a dose of 500mg/Kg of body weight, through intraperitoneal via each 48 hours, for three weeks; Group IV - treated with tyloxapol at a dose of 500mg/Kg of body weight, through intraperitoneal via each 48 hours, for four weeks. Morphological analysis of the aortic arch of the animals from groups II, III and IV, showed similar histological characteristics to group I at intima, media and adventitia tunicas. The intima tunica values at the morphometric study indicated that group III has significant differed from groups I, II and IV. The media and adventitia tunicas values revealed that there were no significant differences between groups I, II, III, and IV. As lipid profile evaluation is concerned, the values of total cholesterol, triglycerides and HDL have indicated... (Complete abstract click electronic access below) / Orientadora: Maria Rita Pacheco / Coorientador: Silvana Martinez Baraldi Artoni / Banca: Lucia Helena Vasques / Banca: Mirela Tinucci Costa / Mestre