Os miomas uterinos são os tumores benignos mais comuns do trato genital feminino, sendo que nas mulheres portadoras, 30% são sintomáticos e exigem alguma forma de tratamento. No presente estudo, foram tratadas 35 pacientes sintomáticas com diagnóstico clínico e ultra-sonográfico de mioma uterino, por meio da embolização dos miomas com partículas de polivinil-álcool associadas à obstrução das artérias uterinas com micromolas fibradas. A avaliação clínica e ecográfica foram inicialmente feitas e o acompanhamento realizado após um, três, seis e doze meses do procedimento. O sucesso técnico foi de 94,3%. O volume uterino médio era de 404,53 cm3 antes do tratamento endovascular percutâneo e o sintoma mais freqüente, em 82,9%, a menorragia. A redução média dos volumes uterinos foi de 21,4%, 39,7%, 53,8% e 59,8% respectivamente em um, três, seis e 12 meses (p < 0,01). Houve, também, a redução do volume do nódulo miomatoso dominante em 5%, 18,5%, 26,8% e 32,9% em um, três, seis e 12 meses, respectivamente (p < 0,01). A melhora e o controle da menorragia foram obtidos em 100% das pacientes tratadas. Houve necessidade de histerectomia em uma paciente por insucesso no controle da dor após seis meses do procedimento. A embolização dos miomas uterinos com partículas de polivinil-álcool associada à oclusão endovascular das artérias uterinas com micromolas fibradas é uma alternativa de tratamento minimamente invasivo para as pacientes sintomáticas portadoras de miomas uterinos que proporciona controle e melhora dos sintomas e redução do tamanho dos miomas e do volume uterino. / Uterine fibroids are the most frequent benign tumors of the female genital tract. The tumors are symptomatic in about 30% of the cases, requiring medical treatment. In the present study, a total of 35 clinically symptomatic patients with ultrasonographic diagnosis of fibroids underwent endovascular treatment, which consisted of embolization of the uterine arteries with 355-500 micras PVA particles associated to metallic coils. Clinical and ultrasonographic evaluations were performed at baseline, 1, 3, 6 and 12 months post-intervention. Technical success was obtained in 94.3% of the cases. Mean uterine volume before the procedure was 404.53 cm³ and menorrhagia was the most frequent symptom (82.9%). Mean reduction of the uterine volumes was 21.4%, 39.7%, 53.8% and 59.8% respectively at 1, 3, 6 and 12 months post-intervention. Dominant fibroid size was also significantly reduced after the procedure (5%, 18.5%, 26.8% and 32.9% reductions at 1, 3, 6 and 12 months, respectively; p < 0.01). Vaginal bleeding was abolished in all cases after the 12-month follow up. One patient needed to undergo hysterectomy 6 months after the procedure due to uncontrolled pain. Our results demonstrate uterine arteries embolization is minimally invasive and provides clinical control of the fibroids associated to significant reduction of the uterine volume. Moreover, the technique preserves the uterus and should be considered a therapeutic alternative to standard surgical treatment.

Made available in DSpace on 2016-07-27T14:20:39Z (GMT). No. of bitstreams: 1 KARINA FERREIRA LEAO.pdf: 931734 bytes, checksum: d9ac2b2c89cc1041418e8622e328e625 (MD5) Previous issue date: 2015-02-26 / Recent studies reveal the high frequency of individuals who are affected by stroke and the cognitive dysfunctions they feature consequently. This paper seeks to assess the cognitive impairments of experiencing a stroke and, more specifically, to evaluate the cognitive performance of people affected by stroke according to hemisphere and artery affected. The paper is divided into two main parts. At first, a theoretical review about the neuropsychological impairments in individuals with stroke was made with the goal of understanding the relationship between brain areas and the cognitive performance of these individuals. For this, a bibliographical survey was conducted in major databases on this subject, describing the theoretical aspects related to Neuroscience, stroke and resulting cognitive dysfunctions assessed by neuropsychological avaliation. It has been found that, as for the etiological description, identification of the types and anatomical structures altered, there is a wide literature, but in relation to cognitive impairment and specific brain areas of research conducted in the field of neurophysiology there is a paucity of publications. Research indicates that it is of fundamental importance more studies intending to show, more and more, the cognitive difficulties in people afflicted with a disease so common in society. Then, in Part 2, an empirical study was conducted with the objective of evaluating the cognitive performance according to hemisphere and artery affected in different neuropsychological tests. Participated in the study 30 patients with a diagnosis of stroke, with the age group between 24-60 years. According to the data, we observe a significant difference according to the lesioned hemisphere only in alternation skills, auditory span, visual-construction, lexical and semantic verbal fluency and verbal comprehension. Regarding to the affected arteries, significant differences were found in selective attention, abstraction, naming, phonetic verbal fluency, verbal comprehension, visual-constructional praxis and recognition of the mnemonic process. The present study as well as providing an understanding of neuropsychological and cognitive impairments of patients injured by stroke, can assist in the development of neuropsychological assessment batteries for people affected by stroke and rehabilitation strategies from possibilities of cognitive dysfunctions according to compromised region after stroke. In general, the two parts of the dissertation contribute to the theoretical extension about cognitive dysfunctions of patients suffering from stroke and consequently the identification of these dysfunctions may thus help to improve care for patients with this disease. / Estudos recentes revelam a alta frequência de indivíduos acometidos por acidente vascular encefálico (AVE) e as disfunções cognitivas que se apresentam em consequência. Esta dissertação buscou avaliar as disfunções cognitivas derivadas da vivência de um AVE e, de forma mais específica, avaliar o desempenho cognitivo de pessoas acometidas por AVE em virtude do hemisfério lesionado e da artéria afetada. A dissertação está dividida em duas partes. Em um primeiro momento, foi realizada uma revisão teórica sobre as alterações neuropsicológicas em indivíduos com AVE, com o objetivo de compreender as relações entre áreas cerebrais e desempenho cognitivo desses indivíduos. Para tanto, foi realizado um levantamento bibliográfico nas principais bases de dados sobre esse tema, com o objetivo de descrever os aspectos teóricos relacionados à Neurociência, o AVE e as decorrentes disfunções cognitivas mediante avaliação neuropsicológica. Verificou-se que, em referência à descrição etiológica, identificação dos tipos e a estruturas anatômicas alteradas, existe uma ampla literatura, porém, em relação a disfunções cognitivas e áreas cerebrais específicas há uma escassez de publicação na área da neuropsicologia. As pesquisas apontam que é de mais fundamental relevância estudos que se proponham a evidenciar cada vez mais as dificuldades cognitivas em pessoas acometidas com uma doença tão frequente na sociedade. Na parte 2, foi realizado um estudo empírico, com o objetivo de avaliar o desempenho cognitivo segundo hemisfério e artéria afetada em diferentes testes neuropsicológicos. Participaram da pesquisa 30 pacientes com diagnóstico médico de AVE, na faixa etária entre 24 e 60 anos. De acordo com os dados, observouse diferença significativa quanto ao hemisfério lesionado nas habilidades de alternância, span auditivo, visuoconstrução, fluência verbal léxica e semântica e compreensão verbal. No que se refere às artérias afetadas, foram encontradas diferenças significativas nas atividades de atenção seletiva, abstração, nomeação, fluência verbal fonética, compreensão verbal, praxia visuoconstrutiva e reconhecimento do processo mnemônico. O presente estudo, além de proporcionar a compreensão de alterações neuropsicológicas e cognitivas dos pacientes lesionados pelo AVE, pode auxiliar o desenvolvimento de baterias de avaliação neuropsicológica para pessoas acometidas por essa doença, bem como estratégias de reabilitação, conforme possibilidades de disfunções cognitivas na região comprometida após a ocorrência do AVE. De maneira geral, as duas partes da dissertação contribuem para a ampliação teórica sobre as disfunções cognitivas de pacientes acometidos por AVE e, consequentemente, para identificação desses comprometimentos, podendo assim auxiliar o atendimento a pacientes com essa enfermidade.

Nos transplantes intervivos de fígado em adultos, o enxerto possui apenas uma artéria segmentar, cujo calibre e extensão são geralmente pequenos. Assim, a distância entre essa artéria do enxerto e a artéria hepática do receptor geralmente é grande e os calibres desproporcionais, tornando tecnicamente difícil a reconstrução arterial hepática. Nestes casos, pode-se utilizar um autoenxerto vascular de interposição para facilitar o procedimento, evitando-se assim complicações cirúrgicas. Objetivo: O presente trabalho se propôs a comparar a artéria mesentérica inferior (AMI), artéria esplênica (AE), artéria epigástrica inferior (AEI), ramo descendente da artéria circunflexa femoral lateral (ACFL) e artéria hepática própria (AHP) como opções de autoenxerto de interposição em transplantes de fígado intervivos em adultos. Método: Foram dissecados 16 cadáveres frescos e coletados as referidas artérias de cada um deles. As variáveis estudadas foram diâmetro do orifício proximal, do distal e comprimento. O diâmetro proximal da AHP e os diâmetros distais AE, AMI, AEI e ramo descendente da ACFL foram comparados ao diâmetro distal da AHD. Os diâmetros proximais e distais da AE, AEI e ramo descendente da ACFL foram comparados entre si para avaliar ganho de calibre. Resultados: Todas as artérias, exceto a AMI, apresentaram diferença estatisticamente significante em relação à AHD quanto à diâmetro. Em termos de ganho de calibre, as artérias apresentaram diferença estatisticamente significante. Todas as artérias, exceto a AHP, apresentaram comprimento de 3 cm. Conclusão: A AMI apresentou a melhor compatibilidade de diâmetro com a AHD e comprimento suficiente para uso como autoenxerto. A AHP, AE, AEI e o ramo descendente da ACFL apresentam calibre estatisticamente diferente da AHD. Destas, somente a AHP não apresentou média de comprimento suficiente para uso em transplante de fígado intervivos / In living donor liver transplantation, the graft presents only a segmental artery, which usually has small diameter and short extension. In these cases, an interpositional arterial autograft can be used in order to obtain vascular extension and better diameter compatibility, making the procedure easier and avoiding surgical complications. Aim: We compared the inferior mesenteric artery (IMA), the splenic artery (SA), the inferior epigastric artery (IEA), the descending branch of the lateral circumflex femoral artery (LCFA) and the proper hepatic artery (PHA) as options of interpositional autograft in living donor liver transplantation. Method: Segments of at least 3 cm of all five arteries were harvested from 16 fresh adult cadavers from both genders through standardized dissection. The analyzed measures were proximal and distal diameter and length. The proximal diameter of RHA and the distal diameter of SA, IMA, IEA and the LCFA were compared to the distal diameter of the RHA. The proximal and distal diameters of the SA, IEA and the LCFA were compared to study caliber gain of each artery. Results: All arteries, except the IMA, showed statistical significant difference in relation to the RHA in terms of diameter. Regarding caliber gain, the arteries demonstrated statistical significant difference. All arteries, except PHA, presented length equal to 3 cm. Conclusion: The IMA demonstrated the best compatibility with the RHA in terms of diameter and has shown sufficient length to be employed as interpositional graft. The PHA, the SA, the IEA and the LCFA presented statistically significant different diameters when compared to the RHA. Among these vessels, only the PHA did not show sufficient mean length

O diabetes mellitus tipo 2 (DM2), uma doença que afeta milhões de pessoas em todo o mundo, é marcado pela presença de complicações micro e macrovasculares, as quais estão associadas à disfunção endotelial, inflamação e fibrose. A aldosterona, cujos níveis plasmáticos estão elevados em pacientes e modelos experimentais de DM2, aumenta a geração de espécies reativas de oxigênio (ERO) e a expressão de marcadores inflamatórios. As citocinas IL-1? e IL-18 são liberadas principalmente após ativação de plataformas moleculares denominadas inflamassomas, as quais incluem os receptores NLRP3. Recentemente, demonstramos que o receptor NLRP3 contribui para a disfunção vascular induzida pela aldosterona. Considerando a existência de evidências que a aldosterona, via receptor mineralocorticoide (MR) e NLRP3, induz a produção de mediadores inflamatórios e, consequentemente, ativação do inflamassoma, podendo assim contribuir para o processo inflamatório no diabetes, nós hipotetizamos que o bloqueio de receptores MR e NLRP3 previne a ativação do inflamassoma e reduz o desenvolvimento das alterações vasculares funcionais associadas ao DM2. Observamos que artérias mesentéricas de animais diabéticos apresentam aumento da expressão/ativação de caspase-1 e IL-11?, aumento dos níveis plasmáticos de IL-1?, aumento da atividade da caspase- 1 em macrófagos do lavado peritoneal e prejuízo no relaxamento dependente de endotélio, comparativamente a artérias do grupo controle. Os tratamentos com espironolactona (antagonista MR) e MCC950 (inibidor de receptor NLRP3) atenuam a disfunção vascular, reduzem a expressão e a atividade da caspase-1 e diminuem os níveis plasmáticos de IL-1?. Células de músculo liso vascular e macrófagos derivados da medula estimulados com aldosterona também apresentam aumento da expressão dos componentes do inflamassoma, o que poderia contribuir para as alterações observadas em animais diabéticos. Pacientes com DM2 apresentam correlação positiva entre os níveis de aldosterona e de IL-1? e/ou glicemia. Em conclusão, nosso estudo demonstra que a aldosterona induz disfunção vascular e processo inflamatório no diabetes tipo 2 através da ativação de MR e do inflamassoma NLRP3. / Type 2 diabetes mellitus (T2DM), a disease that affects millions of people around the world, is marked by the presence of micro and macrovascular complications, which are associated with endothelial dysfunction, inflammation and fibrosis. Aldosterone excess aggravates endothelial dysfunction in diabetes by promoting insulin resistance, fibrosis, oxidative stress and inflammation. Aldosterone activates the molecular platform inflammasome in cells of the immune system, an event that contributes to vascular dysfunction induced by the mineralocorticoid hormone. However, it is unclear whether activation of the inflammasome contributes to the effects of aldosterone in diabetes-associated vascular abnormalities. In the present study we tested the hypothesis that aldosterone induces vascular dysfunction in T2DM via activation of mineralocorticoid receptors (MR) and assembly of the NLRP3 inflammasome. To determine whether aldosterone activates the NLRP3 inflammasome and NLRP3 activation contributes to diabetes-associated vascular dysfunction, mesenteric arteries from control mice (db/m) and mice with type 2 diabetes (db/db), treated with vehicle, spironolactone (MR antagonist) or the NLRP3 antagonist MCC950, were used. Db/db mice exhibited increased vascular expression/activation of caspase-1 and IL-1?, increased plasma IL-1? levels, increased number of caspase-1-positive macrophages in the peritoneal lavage as well as reduced acetylcholine (ACh) vasodilation, compared to control db/m mice. Treatment of db/db mice with spironolactone and MCC950 reduced vascular caspase-1, decreased plasma IL-1? levels and partly restored ACh responses. Spironolactone treatment also reduced the number of caspase-1-positive-macrophages in db/db mice. Vascular smooth muscle cells and bone marrow-derived macrophages stimulated with aldosterone also exhibited increased expression of inflammatory components, which may contribute to diabetes-associated vascular changes. Patients with T2DM exhibited a correlation between aldosterone and IL-1? levels and/or glycemia. In conclusion, our study demonstrates that aldosterone induces vascular dysfunction and inflammatory process in type 2 diabetes through MR receptor activation and NLRP3 inflammation.

A ouabaína (OUA) promoveu hipertensão arterial (HA) após 5, 10 e 20 semanas de tratamento e modificou a função vascular de artérias mesentéricas de resistência (AMR). O tratamento por 5 semanas com OUA aumentou o óxido nítrico (NO) e a expressão protéica da isoforma neuronal de óxido nítrico (nNOS), ao passo que diminuiu os prostanóides vasoconstritores. Além disso, reduziu a expressão protéica da Cu-Zn superóxido dismutase (SOD) e aumentou a atividade funcional da Na+K+-ATPase. Já o tratamento por 10 semanas com OUA aumentou NO e prostanóides vasodilatadores, enquanto diminuiu a expressão protéica da nNOS e da COX-2. O tratamento por 20 semanas reduziu o NO e a expressão protéica da nNOS. Porém, aumentou o ânion superóxido, o tromboxano A2 e a expressão protéica de ambas: a SOD e a COX-2. Em conclusão, o tratamento com OUA promoveu HA e alterações funcionais em AMR, sendo estas dependentes do tempo analisado, pois no tratamento durante 5 e 10 semanas estas alterações não contribuem para a manutenção da HA, enquanto que o tratamento durante 20 semanas contribui. / Ouabain treatment (OUA) developed hypertension after 5, 10 and 20 weeks and modified the vascular function in mesenteric resistance arteries (MRA). 5-weeks treatment with OUA increased nitric oxide (NO) and neuronal isoform of nitric oxide (nNOS) protein expression. On the other side, this treatment reduced vasoconstrictors prostanoids. Besides decreased Cu-Zn superoxide dismutase (SOD) protein expression and increased functional activity of Na+K+-ATPase. 10-weeks treatment enhance NO and vasodilators prostanoids but reduced both nNOS and COX-2 protein expression. 20-weeks treatment reduced NO and nNOS protein expression. Nevertheless increased anion superoxide, tromboxan A2 and both SOD and COX-2 protein expression. In conclusion, OUA treatment induced HA and functional alterations in MRA that are time-dependents, because in 5 and 10 weeks of treatment these alterations are not likely to maintenance of HA, but the changes observed in the treatment during 20 weeks contributes.

Os miomas uterinos são os tumores benignos mais comuns do trato genital feminino, sendo que nas mulheres portadoras, 30% são sintomáticos e exigem alguma forma de tratamento. No presente estudo, foram tratadas 35 pacientes sintomáticas com diagnóstico clínico e ultra-sonográfico de mioma uterino, por meio da embolização dos miomas com partículas de polivinil-álcool associadas à obstrução das artérias uterinas com micromolas fibradas. A avaliação clínica e ecográfica foram inicialmente feitas e o acompanhamento realizado após um, três, seis e doze meses do procedimento. O sucesso técnico foi de 94,3%. O volume uterino médio era de 404,53 cm3 antes do tratamento endovascular percutâneo e o sintoma mais freqüente, em 82,9%, a menorragia. A redução média dos volumes uterinos foi de 21,4%, 39,7%, 53,8% e 59,8% respectivamente em um, três, seis e 12 meses (p < 0,01). Houve, também, a redução do volume do nódulo miomatoso dominante em 5%, 18,5%, 26,8% e 32,9% em um, três, seis e 12 meses, respectivamente (p < 0,01). A melhora e o controle da menorragia foram obtidos em 100% das pacientes tratadas. Houve necessidade de histerectomia em uma paciente por insucesso no controle da dor após seis meses do procedimento. A embolização dos miomas uterinos com partículas de polivinil-álcool associada à oclusão endovascular das artérias uterinas com micromolas fibradas é uma alternativa de tratamento minimamente invasivo para as pacientes sintomáticas portadoras de miomas uterinos que proporciona controle e melhora dos sintomas e redução do tamanho dos miomas e do volume uterino. / Uterine fibroids are the most frequent benign tumors of the female genital tract. The tumors are symptomatic in about 30% of the cases, requiring medical treatment. In the present study, a total of 35 clinically symptomatic patients with ultrasonographic diagnosis of fibroids underwent endovascular treatment, which consisted of embolization of the uterine arteries with 355-500 micras PVA particles associated to metallic coils. Clinical and ultrasonographic evaluations were performed at baseline, 1, 3, 6 and 12 months post-intervention. Technical success was obtained in 94.3% of the cases. Mean uterine volume before the procedure was 404.53 cm³ and menorrhagia was the most frequent symptom (82.9%). Mean reduction of the uterine volumes was 21.4%, 39.7%, 53.8% and 59.8% respectively at 1, 3, 6 and 12 months post-intervention. Dominant fibroid size was also significantly reduced after the procedure (5%, 18.5%, 26.8% and 32.9% reductions at 1, 3, 6 and 12 months, respectively; p < 0.01). Vaginal bleeding was abolished in all cases after the 12-month follow up. One patient needed to undergo hysterectomy 6 months after the procedure due to uncontrolled pain. Our results demonstrate uterine arteries embolization is minimally invasive and provides clinical control of the fibroids associated to significant reduction of the uterine volume. Moreover, the technique preserves the uterus and should be considered a therapeutic alternative to standard surgical treatment.

A hipercolesterolemia familiar (HF) é uma doença autossômica dominante caracterizada por níveis elevados de LDL-c e doença arterial coronária (DAC) precoce. Existem evidências de maior prevalência de aterosclerose subclínica nesta população avaliada pelo escore de cálcio (CAC) e pela espessura íntima-média carotídea (EIMC). O objetivo do nosso estudo foi avaliar aterosclerose subclínica por meio da angiotomografia de coronárias em portadores de HF sem aterosclerose manifesta, correlacionando os achados com parâmetros clínicos, laboratoriais, rigidez aórtica e carotídea e com a EIMC. Incluímos 102 HFs, (45±13 anos, 36% homens, LDL-c 280±54mg/dL) e 35 controles (46±12 anos, 40% homens, LDL-c 103±18mg/dL). O grupo HF apresentava maior carga de placa aterosclerótica representado por: maior número de pacientes com placa (48% versus 14%, p=0,0005), maior número de pacientes com estenose luminal acima de 50% (19% versus 3%, p=0,015), maior número total de segmentos com placas (2,0±2,8 versus 0,4±1,3, p=0,0016), maior número de segmentos com placas calcificadas (0,8±1,54 versus 0,11±0,67, p= 0,0044) e maior escore de cálcio pelo método de Agatston (55±129, mediana:0 versus 38±140, mediana:0; p=0,0028). Houve correlação positiva no grupo HF do número total de segmentos com placa com: idade (r=0,41, p<0,0001), escore de risco de Framingham (r=0,25, p=0,012), colesterol total (r=0,36, p<0,0002), LDL-c (r=0,27, p=0,005), HDL-c (r=0,24, p=0,017), apolipoproteína B (r=0,3, p=0,0032) e escore de cálcio (r=0,93, p<0,0001). Além disso, houve correlação negativa com: variação sísto-diastólica carotídea (r=-0,23, p=0,028) e percentual de distensão carotídeo (r=-0,24, p=0,014). A análise multivariada de determinantes da presença de placa aterosclerótica, revelou que idade (OR=1,105, IC95%: 1,049-1,164, p<0,001) e colesterol total (OR=1,013, IC95%:1,001-1,025) foram as variáveis associadas com a presença da mesma. A única variável associada com presença de obstrução luminal acima de 50% foi o escore de cálcio coronário (OR=1,004; IC95%:1,001-1,008; p=0,014). Em relação a determinantes da composição de placa, na análise multivariada a presença de placa não calcificada esteve associada com o sexo masculino (OR:15,45; IC95%: 1,72-138,23, p=0,014), a placa mista com antecedente familiar de DAC precoce (OR=4,90; IC95%:1,32-18,21, p=0,018) e placa calcificada a menor chance com o sexo masculino (OR=0,21; IC95%: 0,05-0,84, p=0,027). Conclusões: Os pacientes portadores de HF apresentam maior carga de placa avaliada pela angiotomografia em comparação aos controles; idade e colesterol total associaram-se a presença de placas no grupo HF; o escore de cálcio associou-se a presença de estenose luminal acima de 50%. / Familial hypercholesterolemia (FH) is an autosomal dominant disease characterized by high LDL-c levels and premature coronary artery disease (CAD) onset. There is evidence of greater prevalence of subclinical atherosclerosis in this population evaluated by coronary calcium score (CCS) and carotid intima-media thickness (IMT). The aim of our study was to assess subclinical atherosclerosis by computed tomography coronary angiography (CTCA) in patients with FH without manifest atherosclerosis and correlate the findings with clinical and laboratory parameters, aortic and carotid stiffness and IMT. We included 102 FHs (45 ± 13 years, 36% men, LDL-c 280 ± 54mg/dL) and 35 controls (46 ± 12 years, 40% men, LDL-c 103 ± 18mg/dL). The FH group had a greater atherosclerosis plaque burden represented by: higher number of patients with coronary plaque (48% versus 14%, p = 0.0005) and with luminal stenosis greater than 50% (19% versus 3% p = 0.015), higher total number of segments with plaques (2.0 ± 2.8 versus 0.4 ± 1.3, p = 0.0016), higher number of segments with calcified plaques (0.8 ± 1.54 versus 0.11 ± 0.67, p = 0.0044) and higher CCS by the Agatston method (55 ± 129, median: 0 vs. 38 ± 140, median = 0, p = 0.0028). There were positive correlations of total number of segments with plaque in FH group with the following variables: age (r=0.41, p<0.0001), Framingham risk score (r =0.25, p=0.012), total cholesterol (r=0.36, p<0.0002), LDL-c (r=0.27, p=0.005), HDL-c (r=0.24, p=0.017), apolipoprotein B (r=0,3, p=0.0032) and CCS (r=0.93, p<0.0001). In addition there was a negative correlation with: carotid systo-diastolic variation (r=- 0.23, p=0.028) and percentage of carotid distension (r=- 0.24, p=0.014). After multivariate analysis, the determinants of plaque presence were age (OR=1.105, 95% CI=1.049-1.164, p<0.001) and total cholesterol (OR=1.013, 95% CI:1.001-1.025). The only variable associated with presence of luminal stenosis greater than 50% was CCS (OR = 1.004, 95% CI: 1.001-1.008, p=0.014). After multivariate analysis, the presence of non-calcified plaque was associated with male gender (OR: 15.45, 95% CI 1.72-138.23, p = 0.014), mixed plaque with family history of early CAD (OR = 4.90, 95%:1.32-18.21, p=0.018) and calcified plaque negatively with males (OR = 0.21, 95% CI: 0.05-0.84, p = 0.027). Conclusions: FH subjects have higher plaque burden assessed by CTCA compared to controls; age and total cholesterol were associated with the presence of coronary plaque in the FH subjects; CCS was associated with luminal stenosis greater than50%.

Ca2+-activated potassium channels (KCa) and canonical transient receptor potential (TRPC) channels are essential to endothelial function. In ischemic heart disease, or in cardiac surgery, coronary endothelium is subjected to ischemia-reperfusion (I-R) / hypoxia-reoxygenation (H-R) injury. Hyperkalemic cardioplegic or organ preservation solutions used in cardiac surgery including heart transplantation also impair endothelial function. The present study was designed to mainly investigate whether endothelial dysfunction occurring in H-R or in hyperkalemic exposure is attributable to alterations of intermediate- and small-conductance KCa (IKCa and SKCa) channels, or TRPC channels, in particular, the TRPC3 channel. / Exposure to 60-min hypoxia followed by reoxygenation inhibited the vasorelaxant response of coronary arteries to IKCa / SKCa activator 1-EBIO. H-R reduced endothelial IKCa and SKCa currents and downregulated IKCa expression in PCECs. 1-EBIO enhanced endothelial K+ current that was blunted by H-R. / Exposure to hyperkalemic solutions decreased Ca2+ influx via TRPC3 in PCECs. The reduced Ca2+ influx in PCECs and the attenuated EDHF-mediated vasorelaxation in porcine coronary arteries, which were caused by hyperkalemic or cardioplegic / organ preservation solutions, were restored by OAG. / In PCECs, hypoxia for 60-min with reoxygenation reduced TRPC3 current and Ca2+ influx via TRPC3, which was accompanied by decreased NO release and endothelium-dependent vasorelaxation of porcine coronary arteries. The compromised endothelial function was restored by OAG. The translocation of TRPC3 to endothelial membrane was inhibited by H-R. / In TRPC3-overexpressing HEK293 cells, followed by reoxygenation, short-time hypoxia (10-min) enhanced, whereas prolonged hypoxia (60-min) reduced the current induced by TRPC3/6/7 activator OAG. / Our results indicate that: (1) Endothelial IKCa, SKCa and TRPC3 play an important role in regulating vascular tone; TRPC3 contributes to NO release from endothelial cells and is also involved in the function of EDHF. (2) H-R (60-30 min) reduces endothelial IKCa and SKCa currents with downregulation ofthe protein expression of IKCa. (3) H-R has dual effect on TRPC3 with short-time hypoxia (lO-min) enhancing whereas prolonged hypoxia (60-min) decreasing the electrophysiological activity of this channel. H-R (60-30 min) inhibits the translocation of TRPC3 to endothelial membrane. Furthermore, H-R inhibits Ca2+ influx via TRPC3 and such inhibition is associated with a decrease of NO production. (4) The activator of IKCa / SKCa or TRPC protects coronary endothelium against H-R injury. In coronary endothelium exposed to hyperkalemic or cardioplegic / organ preservation solutions, TRPC activator also exhibits protective effect. / The above findings are likely to have significant implications in ischemic heart disease and in modem cardiopulmonary surgery. / Whole-cell membrane currents of IKCa, SKCa, or TRPC3 were recorded by patch-clamp in primary cultured porcine coronary endothelial cells (PCECs). TRPC3 current was also studied in human embryonic kidney cells (HEK293 cells) transiently overexpressed with TRPC3 gene. Protein or mRNA expression of these channels was detected by Western blot or RT-PCR. Intracellular Ca2+ concentration was measured by Ca2+ imaging technique. Isometric force study was performed in a wire myograph and endothelial nitric oxide (NO) release was measured electrochemically by using a NO-specific microsensor in porcine coronary small arteries. / Huang, Junhao. / "December 2010." / Adviser: Qin Yang. / Source: Dissertation Abstracts International, Volume: 73-04, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 138-165). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Wu Min. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (leaves 87-114). / Abstracts in English and Chinese. / Declaration --- p.i / Acknowledgement --- p.ii / Publication list --- p.iii / Abstract (English) --- p.xi / Abstract (Chinese) --- p.xiv / Abbreviations --- p.xvi / List of figures / tables --- p.xviii / Chapter Chapter 1. --- General Introduction --- p.1 / Chapter 1.1 --- Endothelial function in the regulation of vascular tone --- p.1 / Chapter 1.1.1 --- NO --- p.2 / Chapter 1.1.2 --- PGI2 --- p.5 / Chapter 1.1.3 --- EDHF --- p.6 / Chapter 1.2 --- Alteration of endothelial functions after preservation with cardioplegia /organ preservation solutions in the coronary and pulmonary microcirculations --- p.18 / Chapter 1.2.1 --- Cardioplegia/organ preservation solutions --- p.21 / Chapter 1.2.2 --- Effect of Cardioplegia/organ preservation solutions on endothelial function --- p.22 / Chapter 1.2.2.1 --- Effect of K+ on endothelial function --- p.23 / Chapter 1.2.2.2 --- Effect of other components on endothelial function --- p.24 / Chapter Chapter 2. --- Materials and Methods --- p.26 / Chapter 2.1 --- Isometric force study in coronary/pulmonary resistance arteries --- p.26 / Chapter 2.1.1 --- Preparation of vessels --- p.26 / Chapter 2.1.1.1 --- Preparation of porcine coronary small arteries --- p.26 / Chapter 2.1.1.2 --- Preparation of porcine pulmonary small arteries --- p.26 / Chapter 2.1.2 --- Technique of setting up --- p.29 / Chapter 2.1.2.1 --- Mounting of small vessels --- p.29 / Chapter 2.1.2.2 --- Normalization procedure for small vessels --- p.29 / Chapter 2.1.3 --- EDHF-mediated vasorelaxation --- p.30 / Chapter 2.1.3.1 --- Precontraction and stimuli of EDHF --- p.30 / Chapter 2.1.3.2 --- """True"" response of EDHF" --- p.31 / Chapter 2.1.4 --- Data acquisition and analysis --- p.32 / Chapter 2.2 --- Electrophysiological study --- p.32 / Chapter 2.2.1 --- Preparation of small porcine coronary/pulmonary arteries --- p.32 / Chapter 2.2.2 --- Preparation of microelectrode --- p.32 / Chapter 2.2.3 --- Impaling of microelectrode --- p.33 / Chapter 2.2.4 --- Recording of membrane potential --- p.33 / Chapter 2.3 --- Statistical analysis --- p.34 / Chapter 2.4 --- Chemicals --- p.34 / Chapter Chapter 3. --- Effects of Celsior Solution on Endothelial Function in Resistance Coronary Arteries Compared to St. Thomas' Hospital Solution --- p.37 / Chapter 3.1 --- Abstract --- p.37 / Chapter 3.2 --- Introduction --- p.38 / Chapter 3.3 --- Experimental design and analysis --- p.40 / Chapter 3.3.1 --- Vessel preparation --- p.40 / Chapter 3.3.2 --- Normalization --- p.40 / Chapter 3:3.3 --- "Relaxation study: BK-induced, EDHF-mediated relaxation" --- p.41 / Chapter 3.3.4 --- Cellular electrophysiological study: EDHF-mediated cellular hyperpolarization and associated relaxation --- p.41 / Chapter 3.3.5 --- Data analysis --- p.42 / Chapter 3.4 --- Results --- p.43 / Chapter 3.4.1 --- Relaxation study --- p.43 / Chapter 3.4.1.1 --- Resting force --- p.43 / Chapter 3.4.1.2 --- U46619-induced precontraction --- p.43 / Chapter 3.4.1.3 --- EDHF-mediated relaxation --- p.43 / Chapter 3.4.2 --- Electrophysiological studies --- p.44 / Chapter 3.4.2.1 --- Resting membrane potential --- p.44 / Chapter 3.4.2.2 --- EDHF-mediated cellular hyperpolarization --- p.45 / Chapter 3.4.2.3 --- Cellular hyperpolarization-associated relaxation --- p.45 / Chapter 3.5 --- Discussion --- p.46 / Chapter 3.5.1 --- Effects of Celsior solution on endothelial function --- p.47 / Chapter 3.5.2 --- Effects of ST solution on EDHF-mediated function --- p.48 / Chapter 3.5.3 --- Comparison between Celsior and ST solutions on EDHF-mediated function --- p.48 / Chapter 3.5.4 --- Clinical implications --- p.49 / Chapter Chapter 4. --- Effects of Perfadex and Celsior Solution on Endothelial Function in Resistance Pulmonary Arteries --- p.57 / Chapter 4.1 --- Abstract --- p.57 / Chapter 4.2 --- Introduction --- p.58 / Chapter 4.3 --- Experimental design and analysis --- p.59 / Chapter 4.3.1 --- Vessel Preparation --- p.59 / Chapter 4.3.2 --- Normalization --- p.60 / Chapter 4.3.3 --- Isometric force study --- p.60 / Chapter 4.3.4 --- Electrophysiological studies --- p.61 / Chapter 4.3.5 --- Data analysis --- p.61 / Chapter 4.4 --- Results --- p.62 / Chapter 4.4.1 --- Relaxation study: EDHF-mediated relaxation --- p.62 / Chapter 4.4.1.1 --- Resting force --- p.62 / Chapter 4.4.1.2 --- U46619-induced precontraction --- p.62 / Chapter 4.4.1.3 --- EDHF-mediated relaxation --- p.62 / Chapter 4.4.2 --- Electrophysiological studies --- p.63 / Chapter 4.4.2.1 --- Resting membrane potential --- p.63 / Chapter 4.4.2.2 --- EDHF-mediated cellular hyperpolarization --- p.64 / Chapter 4.4.2.3 --- Cellular hyperpolarization-associated relaxation --- p.64 / Chapter 4.5 --- Discussion --- p.65 / Chapter 4.5.1 --- Effects of Celsior solution on endothelial function during cardiopulmonary surgery --- p.65 / Chapter 4.5.2 --- Effects of Perfadex solution on EDHF-mediated endothelial function --- p.66 / Chapter 4.5.3 --- Comparison between Celsior and Perfadex solutions on EDHF-mediated function --- p.66 / Chapter 4.5.4 --- Clinical implications --- p.67 / Chapter Chapter 5. --- Exploration of the Nature of EDHF - the Effect of H2O2 on the Membrane Potential in the Rat Small Mesenteric Arteries --- p.73 / Chapter Chapter 6. --- General Discussion --- p.75 / Chapter 6.1 --- EDHF-mediated endothelial function in porcine coronary and pulmonary circulation --- p.75 / Chapter 6.1.1 --- Role of EDHF in the regulation of porcine coronary arterial tone --- p.75 / Chapter 6.1.2 --- Role of EDHF in the regulation of porcine pulmonary arterial tone --- p.76 / Chapter 6.2 --- Alteration of EDHF-mediated endothelial functions after exposure to organ preservation solutions --- p.77 / Chapter 6.2.1 --- Effects of hyperkalemic solution on EDHF-mediated endothelial function in coronary and pulmonary circulation --- p.78 / Chapter 6.2.2 --- Effects of low-potassium-based preservation solution on EDHF-mediated endothelial function in pulmonary circulation --- p.79 / Chapter 6.2.3 --- Comparison between hyperkalemic solution and low-potassium-based preservation solution on EDHF-mediated endothelial function --- p.80 / Chapter 6.2.4 --- Effects of other component of organ preservation solutions on EDHF-mediated endothelial function --- p.81 / Chapter 6.3 --- Clinical implications --- p.82 / Chapter 6.4 --- The effect of H202 on the membrane potential in rat small mesenteric arteries --- p.83 / Chapter 6.5 --- Limitation of the study --- p.84 / Chapter 6.6 --- Future investigations --- p.85 / Chapter 6.7 --- Conclusions --- p.85 / References --- p.87

Com os avanços tecnológicos das últimas décadas, a ecocardiografia surgiu como uma alternativa de diagnóstico por imagem de relativo baixo custo, que não faz uso de energia ionizante ou radioativa. Recentemente, o advento dos agentes de contraste por microbolhas e dos transdutores matriciais tornou possível a visualização tridimensional da anatomia das artérias coronárias. Neste projeto, é proposta a avaliação de métodos de segmentação capazes de visibilizar as artérias coronárias epicárdicas em Imagens de ecocardiografias tridimensionais com contraste de microbolhas. Esse é o primeiro passo para o desenvolvimento de ferramentas computacionais eficazes e eficientes na assistência não invasiva ao acompanhamento do quadro clínico de pacientes, do diagnóstico ao pós-operatório. Propõe-se, uma metodologia que facilite o acesso às coronárias a partir de imagens de ecocardiografia tridimensionais com aplicação de contraste por microbolhas. Dentre as metodologias estudadas, as técnicas baseadas na teoria Fuzzy Connectedness (FC) foram identificadas como as mais promissoras. Estudou-se, portanto, seis abordagens baseadas nessa teoria, três delas são descritas na literatura (Generalized FC GFC; Relative FC RFC; Dynamic Weighted FC DyWFC) e três proposições originais (Area of Search FC ASFC; Ultrasound-k FC USFC; Guided FC GuFC). Para avaliar a acurácia desses algoritmos, confeccionou-se um conjunto de imagens simuladas, composto por 360 imagens, e selecionou-se um conjunto de imagens de exames reais, composto de 10 imagens reais de pacientes com quadro de Cardiomiopatia Hipertrópica. Para as imagens simuladas, os métodos da literatura alcançaram acurácia de 85,5% para GFC, 89,5% para RFC e 92,0% para DyWFC. Enquanto isso, os métodos propostos alcançaram acurácia de 88,9% para ASFC, 91,7 % para USkFC e 95,2% para GuFC. Para as imagens reais, os métodos convergiram para uma segmentação satisfatória quanto à usabilidade na clínica médica. Esses resultados demonstraram, ainda, o melhor desempenho do método proposto GuFC ante os demais. Dessa forma, ele se torna um candidato para ingressar na etapa de segmentação de uma ferramenta computacional para visibilização das coronárias epicárdicas no futuro / With the technological advances of recent decades, echocardiography has emerged as a relatively low cost imaging diagnostic alternative, that does not use ionizing or radioactive energy. Lately, the advent of microbubble-based contrast agents and array transducers turned possible the visualization of three-dimensional coronary arteries anatomy. The present project proposes to evaluate segmentation methods able to deal with the visualization of the epicardial coronary arteries in microbubble-based three-dimensional echocardiography images. This is the first step towards the development of effective and efficient computational tools for diagnosis and prognosis assistance of cardiac pacient. We propose a methodology to facilitate the access to epicardial coronary arteries in tridimensional echocardiographic images. Among the studied approaches, Fuzzy Connectednessbased segmentation methods were identified as being the most promising. We studied six approaches based on this theory, three of them are described in the literature (Generalized FC GFC; Relative FC RFC; Dynamic Weighted FC DyWFC) and three original contributions (Area of Search FC ASFC; Ultrasound-k FC USFC; Guided FC GuFC). To evaluate the accuracy of these algorithms, a set composed of 360 simulated images were created. We also selected a set of 10 real images, composed of hypertrophic cardiomyopathy patients. For simulated images set, the methods of literature achieved accuracy of 85.5% for GFC, 89,5% for RFC and 92,0% for DyWFC, meanwhile, the proposed method achieved accuracy of 88.9% for ASFC, 91,7 % for USkFC and 95,2% for GuFC. Using the real images set, the methods converged to good results for clinical purposes. These results demonstrate that the proposed method GuFC has shown a better performance than the others, becoming a candidate to the segmentation step in a computational tool for coronary arteries visualization in the future