Diss. (sammanfattning) Stockholm : Karolinska institutet, 2005. / Härtill 4 uppsatser.

A gestação inicial da égua é um período fascinante que abrange numerosas e intensas mudanças em seu desenvolvimento, muitas das quais são únicas para a espécie equina. Esse desenvolvimento depende da manutenção da função lútea, do estabelecimento de um ambiente uterino e de uma interação precisa e orquestrada entre o concepto e o ambiente uterino. O objetivo deste estudo foi verificar as alterações histológicas do endométrio e a produção histotrófica em éguas cíclicas e prenhes nos dias 7, 10 e 13 pós-ovulação. No primeiro ciclo, biópsias endometriais de 30 éguas foram coletadas no dia 7 (n = 10), 10 (n = 10) e 13 (n = 10) constituindo o grupo éguas cíclicas. No segundo ciclo, as mesmas éguas foram cobertas por um garanhão fértil, acompanhadas diariamente até detectar a ovulação, considerada o dia 0. Foram coletadas biópsias endometriais nos dias7 (n 10), 10 (n 10) e 13 (n 10). Imediatamente após a coleta, o útero foi lavado e as éguas em que foi obtido embrião, foram inseridas no grupo de éguas prenhes. Um maior calibre dos vasos sanguíneos foi observado em prenhez comparados às éguas cíclicas do dia 7 aos 13. No sétimo dia pós-ovulação, uma grande perda de células ciliadas foi evidente no grupo de éguas prenhes, comparadas ao grupo de éguas cíclicas, as células do epitélio endometrial estavam mais protusas e uma pequena quantidade de secreção histotrófica entre as dobras endometriais foi observada. No décimo dia de prenhez, secreção histotrófica glandular e do epitélio luminal estavam mais presentes comparadas às éguas do grupo cíclico. No dia 13 de prenhes, foi observado um grande conteúdo de histotrofo nas aberturas glandulares que estavam cercadas por células ciliares. Ocorreram alterações no ambiente uterino logo após a entrada do embrião no útero. No estroma e no lúmen, essas modificações parecem visar fornecer a nutrição necessária para o desenvolvimento inicial do embrião e estas mudanças nas estruturas celulares irão interagir na sinalização embrionária, futura fixação, implantação e placentação. / The early pregnancy of mare is a fascinating period that encompasses numerous and intense changes in its development, many of which are unique to the equine species. This development depends on the maintenance of the luteal function, the establishment of a favorable uterine environment and a precise and orchestrated interaction between the concept and the uterine environment. The aim of this study was to evaluate histological changes in the endometrium in days 7, 10 and 13 post-ovulation in pregnant and cyclic mares. In the first cycle, endometrial biopsies from 30 cyclic mares (Cyclic group) were collected on days 7, 10 and 13 post-ovulation. In the second cycle, the same mares were bred by a fertile stallion. At days 7, 10 and 13 post-ovulation intrauterine biopsies were collected. Immediately after sample collection, the mare‟s uteri were flushed, and those mares with embryo recovery were assigned to the Pregnant group. A larger blood vessel caliber was observed in pregnant mares than in cyclic from day 7 to 13. On the 7th day a large loss of ciliated cells was evident in the group of pregnant mares in comparison with the Cyclic group and the superficial cells of the endometrium were more protruded, and a small amount of histotrophic material between the folds was observed. On the 10th day of pregnancy, the glandular histotrophic secretion and the secretion of luminal epithelium became more intense than the secretion of cyclic mares. On the 13th day of pregnancy, a very large amount of histotroph was observed within large glandular openings surrounded by ciliated cells. Changes occurred in the uterine environment thereupon the entry of the embryo into the uterus. In the stroma and in the lumen, these modifications seem aim to provide the necessary nutrition for the initial development of the embryo and to promote changes at cellular structures that will interact in the embryonic signaling and future fixation, implantation and placentation.

Made available in DSpace on 2014-12-17T15:32:20Z (GMT). No. of bitstreams: 1 DeniseHIPO_DISSERT.pdf: 4556175 bytes, checksum: 89c325ea02bf77fa8472508c05c7634d (MD5) Previous issue date: 2012-02-16 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / The correct histological diagnosis of vascular lesions in the oral mucosa is critical, especially in defining the treatment and prognosis, as some vascular lesions show spontaneous involution and others do not show such behavior. This study analyzed the expression immunohistochemistry of human glucose transporter protein (GLUT-1), in oral benign vascular tumors and to reclassify such lesions according to with his immunoexpression. In addition, we evaluated the immunohistochemical expression of hypoxia-inducible factor 1 alpha (HIF-1?), the main transcription factor involved in cellular adaptation to hypoxia. We analyzed 60 cases of benign oral vascular tumors: 30 cases with histological diagnosis of HEM and 30 cases of oral pyogenic granuloma (PG). The results of this research showed that of the 30 lesions initially classified as HEM, only 7 showed immuno-positivity for GLUT-1, remaining with the initial diagnosis. The remaining 23 were reclassified as vascular malformation (VM) (13 cases) and PG (10 cases). All cases in the sample with an initial diagnosis of PG were negative for GLUT-1, demonstrating the accuracy of histological diagnosis of these lesions. Concerning to the immunoexpression of HIF-1?, the Mann-Whitney test revealed a statistically significant difference between the cases of GP and MV (p = 0.002), where the median of GP (m=78) was higher than the MV (m=53). Based on these results, this study showed that a histological diagnosis alone is not always sufficient for the correct diagnosis of oral HEM and that HIF-1? participates in the pathogenesis of vascular lesions / O correto diagn?stico histol?gico de les?es vasculares em mucosa oral ? fundamental, sobretudo na hora de definir o tratamento e progn?stico, visto que algumas dessas les?es apresentam involu??o. Este trabalho analisou a express?o imunohistoqu?mica da prote?na humana transportadora de glicose (GLUT-1), em tumores vasculares benignos orais e reclassificou tais les?es de acordo com sua imunoexpress?o. Al?m disso, avaliou a express?o imuno-histoqu?mica do fator 1 induz?vel por hip?xia (HIF-1?), principal fator de transcri??o envolvido na adapta??o celular ? hip?xia. Foram analisados 60 casos de tumores vasculares benignos orais, sendo 30 casos com diagn?stico histol?gico de HEM e 30 casos de granulomas piog?nicos orais (GP). Os resultados desta pesquisa demonstraram que das 30 les?es inicialmente classificadas como HEM, apenas 7 apresentaram imuno-positividade para GLUT-1, permanecendo com o diagn?stico inicial. As 23 restantes foram reclassificadas em malforma??o vascular (MV) 13 casos e GP 10 casos . Todos os casos da amostra com diagn?stico inicial de GP apresentaram-se negativos para GLUT-1. Quanto ? imunoexpress?o do HIF-1?, o teste de Mann-Whitney revelou diferen?a estatisticamente significativa entre os casos de GP e MV(p=0,002), onde a mediana do GP (m=78) foi superior a da MV (m=53). Com base nesses resultados, este estudo mostrou que o diagn?stico histol?gico por si s? nem sempre ? suficiente para o diagn?stico correto do HEM oral e que o HIF- 1? participa da patog?nese das les?es vasculares

Optical coherence tomography (OCT) is a safe and non-invasive imaging technique providing high axial resolution. A spectral-domain OCT scanner capable of acquiring volumetric data of the retina is becoming an increasingly important modality in ophthalmology for the diagnosis and management of a variety of retinal diseases such as glaucoma, diabetic retinopathy and age related macular degeneration (AMD) which are major causes of a loss of vision. To analyze and track these ocular diseases, developments of the automated methods for detecting intraretinal layers, optic discs and retinal blood vessels from spectral-domain OCT scans are highly required recently. The major contributions of this thesis include: 1) developing a fast method that can automatically segment ten intraretinal layers in the spectral-domain macular OCT scan for the layer thickness analysis, 2) developing a method that can automatically segment the optic disc cup and neuroretinal rim in the spectral-domain OCT scan centered at the optic nerve head (ONH) to measure the cup-to-disc ratio, an important structural indicator for the progression of glaucoma, and 3) developing a method that can automatically segment the 3-D retinal blood vessels in the spectral-domain ONH-centered OCT scan to extract 3-D features of the vessels for the diagnosis of retinal vascular diseases.

Blood vessel mimics (BVMs) are simple tissue engineered blood vessel constructs intended for preclinical testing of vascular devices. This thesis developed and implemented methods to characterize two of these components. The first aim of this thesis investigated the effect of cell culture duration and flow conditions on endothelial cell gene expression, especially regarding endothelial-to-mesenchymal transition (EndMT). A trend of decreased endothelial marker gene expression and increased mesenchymal marker gene expression would indicate EndMT. qPCR analysis revealed that increased cell culture duration did not result in EndMT, and in fact increased endothelial marker expression as cell culture duration increased. Disturbed flow conditions decreased endothelial marker and increased mesenchymal marker expression relative to static culture. The second aim of this thesis developed methods to determine cytotoxicity of, and endothelial cell adhesion to, novel BTEAC salt scaffolds. Immunostaining was used to visualize these scaffold effects. The cytotoxicity elution assay showed that BTEAC salt scaffolds were not more cytotoxic than the standard PLGA scaffold. Direct contact assays spanning several timepoints also found that BTEAC salt scaffolds were not more cytotoxic than standard scaffolds but had higher endothelial cell adhesion and coverage than standard scaffolds. Overall, this thesis developed and implemented methods to characterize the endothelial cells used in the BVM model.

No description available.

Objetivo: Medir a pulsatilidade da parede do aneurisma de aorta humano antes e depois de sua correção endoluminal. Método: Cinco aneurismas foram submetidos à perfusão pulsátil antes e depois do implante de uma endoprótese. Resultado: o nível da coluna de água oscilou durante a pulsação com variações de 17, 16, 13, 7 e 25 cm antes da colocação da endoprótese. Depois da prótese, a oscilação diminuiu em todos os casos para 13, 12, 9, 3,5 e 23 cm, respectivamente. Conclusão: A pulsação da endoprótese é transmitida à parede do aneurisma / Objective: To measure the pulsatility of human aortic aneurysms before and after exclusion with endograft. Method: Five aneurysms were submitted to pulsatile perfusion before and after implantation of a bifurcated endograft. Result: The level of the water column oscillated during pulsation, in each case, with an amplitude of 17, 16, 13, 7 and 25 cm before the endograft insertion. After that, the amplitudes dropped to, respectively 13, 12, 9, 3.5 and 23 cm.Conclusion: Pulsation of an endograft is transmitted to the aneurysm wall even in the absence of endoleak

Submitted by Fabíola Silva (fabiola.silva@famerp.br) on 2017-05-25T19:30:55Z No. of bitstreams: 1 antoniocarlosbrandi_tese.pdf: 1540715 bytes, checksum: 85572fb595b07fb61d81ed453db08401 (MD5) / Made available in DSpace on 2017-05-25T19:30:55Z (GMT). No. of bitstreams: 1 antoniocarlosbrandi_tese.pdf: 1540715 bytes, checksum: 85572fb595b07fb61d81ed453db08401 (MD5) Previous issue date: 2015-05-20 / Introduction: Thoracic aortic diseases, including dissections, aneurysms, pseudoaneurysms among other, are serious conditions that bring serious risks of morbidity and mortality. Its incidence is low, but has been growing gradually due to the increase in life expectancy of the population, that in most cases, is associated with hypertension, smoking and diabetes mellitus. Advances in diagnostic techniques have also contributed to the identification of an increasing number of cases. The development of minimally invasive endovascular procedures has been used successfully in the treatment of these diseases, including patients with no indication for conventional surgical treatment. Objective: Evaluate the long-term results of endovascular treatment of patients with diseases of the thoracic aorta underwent implantation of self-expandable stent-grafts. Methods: This prospective study evaluated 112 patients who underwent percutaneous implantation of endoprosthesis of the thoracic aorta, from October 1998 to August 2013. Self-expandable endoprosthesis stent-graft Braile Biomédica ®, made of stainless steel and nitinol were employed. The occurrence of intraoperative and postoperative primary success, endoleaks, mortality, late evolution of the endoprosthesis and survival were evaluated in long term follow-up. Results: The mean time of the procedures was 72.66 ± 43.36 minutes (range 30-240 minutes). A total of 150 self-expandable stents were implanted in 112 patients, 61 (40.66%) of stainless steel and 89 (59.33%) of nitinol. The diameter and length of the stents of stainless steel and nitinol ranged from 24-45 mm (median 33) and 70-130 mm (median 90) 22-46 mm (median 35) and between 40 and 230 mm (median 110) respectively. The number of stents implanted per patient ranged from 1 to 4 (median 1). Primary success was observed in 100 (82.14%) of 112 patients treated. Immediate mortality occurred in seven (6.25%) patients, five (4.46%) from cardiovascular causes and two (1.78%) for non-cardiovascular causes. Late mortality occurred in 31 (27.68%) patients, 10 (8.93%) from cardiovascular causes, 12 (10.71%) for non-cardiovascular causes, two (1.78%) from natural causes-seven (6.25%) with no diagnosis. There hospital type I endoleaks occurred in four patients (3.57%), type II in five (4.46%) and three type IV (2.68%). Late endoleaks type I occurred in five (4.46%) patients and type IV in three (2.68%). Twenty-two patients (19.64%) had clinical complications in the immediate postoperative period, including nine (8.03%) pulmonary complications, four (3.57%) neurological abnormalities, three (2.67%) acute renal failure, two (1.78%) infections in the surgical incision, two (1.78%) with progression to post-implantation syndrome and one (0.89%) with laceration of the arterial access. Follow-up time ranged from 1 to 179 months (median 46). The acturial survival curve was 79,3% (IC95% 67,0-91,7) at 132 months free of death from cardiovascular causes. The logistic regression analysis showed that renal failure was the only risk factor that showed a statistically significant difference. Conclusions: The low levels of intra and postoperative complications demonstrate that the treatment is safe and effective. The high rate of survival after 132 months of follow-up for these critically ill patients show the benefits of endovascular technique to treatment of thoracic aorta diseases. / Introdução: Doenças da aorta torácica, incluindo as dissecções, aneurismas, pseudoaneurismas entre outras, são condições graves que trazem sérios riscos de morbimortalidade. Sua incidência é baixa, porém, vem crescendo gradativamente em virtude do aumento da expectativa de vida da população que, na maioria dos casos, está associada à hipertensão arterial, tabagismo e diabetes. Os avanços nas técnicas diagnósticas também têm contribuído para a identificação de um número cada vez maior de casos. O desenvolvimento de procedimentos endovasculares minimamente invasivos vem sendo utilizado com sucesso no tratamento destas doenças, inclusive em pacientes sem indicação para tratamento cirúrgico convencional. Objetivo: Avaliar os resultados em longo prazo do tratamento endovascular de pacientes portadores de doenças da aorta torácica submetidos ao implante de endopróteses autoexpansíveis stent-grafts. Casuística e Métodos: Estudo prospectivo que avaliou 112 pacientes submetidos ao implante percutâneo de endoprótese na aorta torácica, no período de outubro de 1998 a agosto de 2013. Foram empregadas endopróteses autoexpansíveis stent-grafts da Braile Biomédica®, confeccionadas em aço inox e nitinol. Foram avaliadas a ocorrência de complicações intra e pós-operatórias, sucesso primário, endoleak, mortalidade, evolução tardia da endoprótese e a sobrevivência em seguimento de longo prazo. Resultados. O tempo médio dos procedimentos foi de 72,66±43,36 minutos (variação 30-240 minutos). Foram implantadas um total de 150 endopróteses autoexpansíveis em 112 pacientes, sendo 61 (40,66%) de aço inox e 89 (59,33%) de nitinol. O diâmetro e comprimento dos stents de aço inox e de nitinol variaram de 24-45 mm (mediana 33) e 70-130 mm (mediana 90), 22-46 mm (mediana 35) e 40 a 230 mm (mediana 110), respectivamente. O número de endopróteses implantadas por paciente variou de 1 a 4 (mediana 1). Sucesso primário foi observado em 100 (82,14%) dos 112 pacientes tratados. A mortalidade hospitalar ocorreu em sete (6,25%) pacientes, cinco (4,46%) por causas cardiovasculares e dois (1,78%) por causas não cardiovasculares. A mortalidade tardia ocorreu em 31 (27,68%) pacientes, 10 (8,93%) por causas cardiovasculares, 12 (10,71%) por causas não cardiovasculares, dois (1,78%) por causas naturais e sete (6,25%) sem diagnóstico. No período hospitalar, ocorreu endoleak do tipo I em quatro pacientes (3,57%), tipo II em cinco (4,46%) e tipo IV em três (2,68%). Endoleak tardio do tipo I ocorreu em cinco (4,46%) pacientes e do tipo IV em três (2,68%). Vinte e dois pacientes (19,64%) apresentaram complicações clínicas no pós-operatório imediato, incluindo nove (8,03%) complicações pulmonares, quatro (3,57%) alterações neurológicas, três (2,67%) pacientes com insuficiência renal aguda, duas (1,78%) incisões cirúrgicas com infecção, duas (1,78%) síndromes pós-implante e uma (0,89%) laceração do acesso arterial. O tempo de seguimento variou de 1 a 179 meses (mediana 46). A curva atuarial de sobrevivência foi de 79,3% (IC95% 67,0-91,7) aos 132 meses livre de mortalidade por causas cardiovasculares. A análise de regressão logística mostrou que a insuficiência renal foi o único fator de risco para mortalidade que apresentou diferença estatisticamente significante. Conclusões. Os baixos índices de complicações intra e pós-operatórias demonstram que o tratamento é seguro e eficaz. O alto índice de sobrevivência após 132 meses de seguimento para estes pacientes graves mostram os benefícios da técnica endovascular no tratamento das doenças da aorta torácica.

<p>Formation of blood vessels occurs through two processes: vasculogenesis and angiogenesis, which are regulated by various growth factors such as vascular endothelial growth factor, fibroblast growth factor and platelet-derived growth factor. The present study was carried out in order to investigate the roles of the Shb and Cbl proteins in growth factor-mediated signal transduction and blood vessel formation. Shb was found to be involved in NGF-stimulated Rap1 signaling in PC12 cells by forming a complex with CrkII and a 130-135 kDa protein. The Rap1 signaling pathway contributed to NGF-dependent neurite outgrowth. In immortomouse brain endothelial (IBE) cells, Shb increased cell spreading, migration and cytoskeletal rearrangements. Such effects may partly be due to altered Rap1 activation in Shb overexpressing IBE cells. Shb was required for tubular morphogenesis in collagen gels in the presence of FGF-2. In embryoid bodies (EBs) derived from murine embryonic stem cells, Shb up-regulated both VEGFR2 and Tal1 expression at early stages of EB development and thus promoted blood vessel formation both in the absence and in the presence of growth factors. In IBE cells, Cbl positively regulated FGF-2 signaling and increased cell proliferation. Mutation of RING finger alone did not affect blood vessel formation in EBs. However, EBs overexpressing the oncogenic form Cbl 70Z, which had a deletion of the linker region and the first cysteine of the RING finger, exhibited intense CD31 positive sheet-like staining and blood vessel. The results suggested that Cbl had dual roles in endothelial cells: it promoted FGF-2-induced proliferation whereas down-regulated proliferation of endothelial progenitor cells.</p><p>The present work suggests that Shb and Cbl play a crucial role in cell differentiation and blood vessel formation.</p>

Formation of blood vessels occurs through two processes: vasculogenesis and angiogenesis, which are regulated by various growth factors such as vascular endothelial growth factor, fibroblast growth factor and platelet-derived growth factor. The present study was carried out in order to investigate the roles of the Shb and Cbl proteins in growth factor-mediated signal transduction and blood vessel formation. Shb was found to be involved in NGF-stimulated Rap1 signaling in PC12 cells by forming a complex with CrkII and a 130-135 kDa protein. The Rap1 signaling pathway contributed to NGF-dependent neurite outgrowth. In immortomouse brain endothelial (IBE) cells, Shb increased cell spreading, migration and cytoskeletal rearrangements. Such effects may partly be due to altered Rap1 activation in Shb overexpressing IBE cells. Shb was required for tubular morphogenesis in collagen gels in the presence of FGF-2. In embryoid bodies (EBs) derived from murine embryonic stem cells, Shb up-regulated both VEGFR2 and Tal1 expression at early stages of EB development and thus promoted blood vessel formation both in the absence and in the presence of growth factors. In IBE cells, Cbl positively regulated FGF-2 signaling and increased cell proliferation. Mutation of RING finger alone did not affect blood vessel formation in EBs. However, EBs overexpressing the oncogenic form Cbl 70Z, which had a deletion of the linker region and the first cysteine of the RING finger, exhibited intense CD31 positive sheet-like staining and blood vessel. The results suggested that Cbl had dual roles in endothelial cells: it promoted FGF-2-induced proliferation whereas down-regulated proliferation of endothelial progenitor cells. The present work suggests that Shb and Cbl play a crucial role in cell differentiation and blood vessel formation.