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The main goal of this diploma thesis was the stress-strain analysis of iliac artery with atheroma.This problem was solved using finite element method (FEM).For the calculation purposes three two-dimensional models were created. The geometry was gained from transversal sections through the iliac artery with ateroma. This geometry is educed from used literature review. The main calculation process was run by ANSYS 11.0 program system.

Atherosclerosis causes hundreds of thousands of deaths in the US alone every year. Fibrous cap rupture is one of the leading causes of these fatalities. Thin cap atheromas are commonly regarded as vulnerable plaque, however the effect of calcium upon a thin fibrous cap with lipid pool is poorly understood. Some studies have shown that calcium adds to stability of the lesion, while others have proven otherwise. An article by Li et al. 2007 suggests location is the key factor. By varying the percentage of calcium and lipid within a defined region, the stress on the cap was estimated using an idealized finite element arterial model. Also the thickness of the fibrous cap was varied to determine whether the stress was solely a function of lipid percentage or a combination. Plaque, arterial wall, lipid, and calcium were modeled using linear elastic, isotropic, and incompressible material properties. The first test varied the thin cap thickness from 65 to 500 microns and tested the calcified lipid model at varying lipid/calcium percentages. The lipid/Calcium pool increased/decreased 10% each test. As the cap thickness becomes thinner than 100 microns, the stress level increases rapidly. The second test compared a model with lipid pool and calcium behind the lipid with a thin cap of 65 microns to a model with lipid pool of the same size and thin cap of 65 microns but only fibrous tissue surrounding (no calcium). The lipid pool increased from 10 to 90% lipid. The result of this test found that at higher lipid percentages, the calcium increased the stress on the cap. By understanding the material properties of plaque and the structure of the lesion, future developments may be able to evaluate rupture risk. This idealized study illustrates the ability of computation models to provide insight into clinical situations.

Periodontal diseases may increase risk of vascular calcification in cardiovascular diseases but the potential mechanisms are not defined. Fetuin, a naturally-occurring serum glycoprotein in humans, protects against ectopic arterial calcification. We considered that patients with periodontitis could be at increased risk of developing calcifying atheromas because periodontal-disease associated enzymes may enter the circulation and subsequently degrade fetuin, thereby disrupting its ability to inhibit calcification. By in silico investigation, MMP -3 and -7 were predicted to cleave fetuin but only MMP-7 actually degraded human fetuin in vitro. MMP-7 degradation of fetuin was time- and concentration- dependent and was inhibited by an MMP Inhibitor. By mass spectrometry the presence of novel, MMP-7-mediated cleavage sites in fetuin were found. Fetuin bound tightly to MMP-7 (kd =2.96 x 10-9 M). The degradation of fetuin by MMP-7 could explain, at least in part, the apparent association between periodontal diseases and calcifying atheromas.

Periodontal diseases may increase risk of vascular calcification in cardiovascular diseases but the potential mechanisms are not defined. Fetuin, a naturally-occurring serum glycoprotein in humans, protects against ectopic arterial calcification. We considered that patients with periodontitis could be at increased risk of developing calcifying atheromas because periodontal-disease associated enzymes may enter the circulation and subsequently degrade fetuin, thereby disrupting its ability to inhibit calcification. By in silico investigation, MMP -3 and -7 were predicted to cleave fetuin but only MMP-7 actually degraded human fetuin in vitro. MMP-7 degradation of fetuin was time- and concentration- dependent and was inhibited by an MMP Inhibitor. By mass spectrometry the presence of novel, MMP-7-mediated cleavage sites in fetuin were found. Fetuin bound tightly to MMP-7 (kd =2.96 x 10-9 M). The degradation of fetuin by MMP-7 could explain, at least in part, the apparent association between periodontal diseases and calcifying atheromas.

FUNDAMENTO: O suco de laranja (Citrus sinensis) é rico em vitami-na C, folatos e seu principal flavonóide, a hesperidina, cuja conformação es-pacial é semelhante à genisteína de soja que tem ação favorável sobre o aparelho cardiovascular. A vitamina C é conhecida como potente inibidor da peroxidação lipídica. Mas sua capacidade por possuir efeitos terapêuticos no tratamento da aterosclerose é pouco estudada. OBJETIVO: O presente tra-balho visa a determinar se o suco de laranja pode ter efeito aditivo no trata-mento com estatinas e fibratos, reduzindo placas ateroscleróticas e a quanti-dade de LDL Oxidado (LDL ox). MÉTODOS: Análise do efeito do suco nas dimensões de cortes histológicos e na quantidade de anticorpos anti LDL oxidado (antiLDLox) em lesões ateroscleróticas na aorta de coelhos. RE-SULTADOS: O suco de laranja potencializou a redução de área de placas ateroscleróticas e a quantidade de LDL(ox) em relação às reduções obtidas com rosuvastatina e gemfibrozil. CONCLUSÕES: O suco de laranja tem efei-to sinérgico ao tratamento convencional da aterosclerose de coelhos / Statins and fibrates have been used as anti-atherosclerotic drugs. However, a high number of treated patients still present acute events and death by atherosclerotic complications. Flavonoid ingestion has been associ-ated with lower risk of death, lower incidence of coronary artery disease and more preserved endothelial function in atherosclerotic patients. Orange juice is rich in C vitamine, a well known potent inhibitor of lipidic peroxidation, and in flavonoids, mainly the hesperidine that seems the soy bean genisteine, which is associated with decrease LDL and increase HDL. Objective: In this work we studied if orange juice has addictive effect to statin and gemfibrozil in the treatment of rabbit atherosclerosis, reducing plaque area and oxidate LDL (LDLox). Methods: Five group of atherosclerotic rabbits, fed with 1% cholesterol enriched diet during 12 weeks, were analyzed: GI - received no treatment, GII Gemfibrozil 600mg/day, GIII treated with Gemfibrozil 600mg/day + orange juice, GIV - rosuvastatin/10mg / day and GV - rosu-vastatin/10mg / day + orange juice. The most severe atherosclerotic cross section in ascendant aorta was analyzed in H&E and anti-oxidated LDL (oxLDL) immunostained slides, obtaining intimal area, total vessel area, % luminal obstruction and % oxLDL area in intima. Results: The means (stan-dard deviations) of plaque area and % plaque area of oxLDL in GI were 1.05 (0.91) and 0.12 (0.13), with no significant difference with GII animals, respec- tively 3.85 (5.27) and 0.18 (0.22), but significantly reduced in GIII, 0.64 (1.56) and 0.03 (0.05). Similar data were seen in GIV, 2.11 (2.77) and 0.19 (0.25), compared with GV, 0.04 (0.09) and 0.00 (0.00). Conclusion: This work de-monstrates that orange juice has a potential synergistic action with statin and fibrates in reducing atherosclerosis and the mechanism seems to involve in-hibition of oxLDL concentration and migration of smooth muscle cells in the subendothelial space

Estudos recentes sugeriram associação entre doença periodontal e doenças cardiovasculares e respiratórias. O objetivo deste estudo foi investigar a presença de bactérias periodontopatogênicas em placas ateromatosas humanas. Foram incluídos no estudo 24 pacientes de ambos os sexos, 40-60 anos de idade, internados na UTI do Hospital Nossa Senhora da Conceição em Tubarão-SC com indicação para endarterectomia. Após a coleta das placas ateromatosas, procedeu-se a identificação de sete diferentes espécies bacterianas periodontopatógenos por meio da reação em cadeia da polimerase em tempo real (RT-PCR). Para realização da análise estatistica foi verificada a associação entre as duas variáveis qualitativas nominais (presença ou ausência de bácterias X tipo de bactérias) por meio do teste Qui-quadrado, com nível designificância de 5 %. Os resultados desse trabalho mostraram haver associação entre presença ou ausência de bactérias e dos diferentes tipos de bactérias nos ateromas analisados (p = 0001). Dos ateromas avaliados 75% apresentaram Porphyromonas gingivalis., 58,3% Treponema denticola., 37,5% apresentaram Fusobacteriumnucleatum., 33,3% Prevotella intermedia., 20,8% Agreggatibacter actinomycetencomitanse. 0,4% de Prevotella nigrescens. Esses achados permitem concluir que bactérias periodontopatogênicas apresentam a capacidade de invadir a parede das artérias, podendo ter papel significativo no desenvolvimento ou ruptura das placas ateroescleróticas. / Recent studies suggested an association between periodontal disease and cardiovascular and respiratory diseases. The aim of this study was to investigate the presence of periodontopathogens in human atherosclerotic plaque. It were included in this study 24 non-smoking patients, both genders, 40-60 years, admitted at intensive unit care with indication of endarterectomy. After collection of carotid samples containing the lesions, the identification of seven different bacterial species was performed by real time polymerase chain reaction (RT-PCR). For statistical analysis, the association between two nominal qualitative variables (presence or absence of bactérias vs. bacterial specieis) was verified by Chi-squared test, with a 5% significance level. The results obtained showed an association between the presence or absence and bacterial species found in atheroma (p= .0001). Among the atheroma examined, 75% showed the presence of Porphyromonas gingivalis, 58.3% showed Treponema denticola, 37.5% showed Fusobacteriumnucleatum, 33.3% showed Prevotella intermedia, 20.8% Agreggatibacter actinomycetencomitans and 0.4% Prevotella nigrescens. These findings suggest that periodontopatoghens are capable of invading artery wall and could play a significant role in the development or rupture of atherosclerotic lesions.

A identificação de ateroma de carótida em radiografia panorâmica de pacientes com alterações sistêmicas que predispõem a aterosclerose é mais frequente do que em amostras da população em geral. O uso da terapia antirretroviral combinada (TARVc), que prolongou a sobrevida dos pacientes portadores do HIV (HIV+), também contribuiu para o aumento da incidência de alterações metabólicas e provavelmente de complicações cardiovasculares. Este estudo teve o objetivo de investigar a prevalência de imagens suspeitas de ateromas de carótida (ISAC) em radiografias panorâmicas de pacientes HIV+ em tratamento no Centro de Atendimento de Pacientes Especiais (CAPE) da Faculdade de Odontologia da Universidade de São Paulo, bem como tentar identificar variáveis associadas à ocorrência destas imagens. Foram avaliadas 300 radiografias de pacientes de ambos os gêneros e com média de idade de 40 anos (18-73 anos). A prevalência de radiografias com ISAC foi de 8,2% (25/300). Estes pacientes apresentaram a média de idade significativamente maior do que a dos pacientes sem ISAC (p= 0,008) e a mediana do nadir de CD4 significativamente menor (p=0,019). O uso do medicamento lopinavir/r (LPV/r) estava associado a chance 2,8 vezes maior para presença de ISAC (OD=2,79 1,12-6,95 IC=95%, p=0,045). Conclui-se que quanto maior a idade maior a probabilidade de ocorrência de ISAC e que as variáveis significativas encontradas (nadir de CD4 e LPV/r) são compatíveis com os fatores de risco cardiovascular observados em pacientes portadores do HIV, relacionados tanto à gravidade da infecção como ao uso de medicamentos. / The identification of calcified carotid artery atheroma (CCAA) in panoramic radiography of patients with systemic diseases that predispose the atherosclerosis is more frequent than in the general population samples. The use of high active antiretroviral therapy (HAART), which prolonged the life of patients with HIV (HIV+), also increase the incidence of cardiovascular complications, probably by the use of protease inhibitors (PI). This study aimed to investigate the prevalence of suspected images of CCAA in panoramic radiographs of HIV+ patients in treatment in the Special Care Dentistry Center of the University of São Paulo, São Paulo, Brazil, as well as trying to identify variables associated with these images. Three hundred radiographs of patients of both genders, with a mean age of 40 years (18-73 years) were evaluated. The prevalence of CCAA suspected images was 8.2% (25/300). This patients showed the mean age significantly higher than that of the patients without CCAA images (p = 0.008) and the CD4 nadir median significantly lower (p = 0.019). The use of HAART with lopinavir/r (LPV/r) was associated with a greater chance for CCAA images (OD 2.79, CI 95% 1.12-6.95; p = 0.045). In conclusion, patients with higher age are more susceptible to CCAA suspected image and the significant variables found (CD4 nadir and LPV/r) are compatible with the cardiovascular risk factors in patients HIV+, related both to the severity of the infection and the use of antiretroviral.

A identificação de ateroma de carótida em radiografia panorâmica de pacientes com alterações sistêmicas que predispõem a aterosclerose é mais frequente do que em amostras da população em geral. O uso da terapia antirretroviral combinada (TARVc), que prolongou a sobrevida dos pacientes portadores do HIV (HIV+), também contribuiu para o aumento da incidência de alterações metabólicas e provavelmente de complicações cardiovasculares. Este estudo teve o objetivo de investigar a prevalência de imagens suspeitas de ateromas de carótida (ISAC) em radiografias panorâmicas de pacientes HIV+ em tratamento no Centro de Atendimento de Pacientes Especiais (CAPE) da Faculdade de Odontologia da Universidade de São Paulo, bem como tentar identificar variáveis associadas à ocorrência destas imagens. Foram avaliadas 300 radiografias de pacientes de ambos os gêneros e com média de idade de 40 anos (18-73 anos). A prevalência de radiografias com ISAC foi de 8,2% (25/300). Estes pacientes apresentaram a média de idade significativamente maior do que a dos pacientes sem ISAC (p= 0,008) e a mediana do nadir de CD4 significativamente menor (p=0,019). O uso do medicamento lopinavir/r (LPV/r) estava associado a chance 2,8 vezes maior para presença de ISAC (OD=2,79 1,12-6,95 IC=95%, p=0,045). Conclui-se que quanto maior a idade maior a probabilidade de ocorrência de ISAC e que as variáveis significativas encontradas (nadir de CD4 e LPV/r) são compatíveis com os fatores de risco cardiovascular observados em pacientes portadores do HIV, relacionados tanto à gravidade da infecção como ao uso de medicamentos. / The identification of calcified carotid artery atheroma (CCAA) in panoramic radiography of patients with systemic diseases that predispose the atherosclerosis is more frequent than in the general population samples. The use of high active antiretroviral therapy (HAART), which prolonged the life of patients with HIV (HIV+), also increase the incidence of cardiovascular complications, probably by the use of protease inhibitors (PI). This study aimed to investigate the prevalence of suspected images of CCAA in panoramic radiographs of HIV+ patients in treatment in the Special Care Dentistry Center of the University of São Paulo, São Paulo, Brazil, as well as trying to identify variables associated with these images. Three hundred radiographs of patients of both genders, with a mean age of 40 years (18-73 years) were evaluated. The prevalence of CCAA suspected images was 8.2% (25/300). This patients showed the mean age significantly higher than that of the patients without CCAA images (p = 0.008) and the CD4 nadir median significantly lower (p = 0.019). The use of HAART with lopinavir/r (LPV/r) was associated with a greater chance for CCAA images (OD 2.79, CI 95% 1.12-6.95; p = 0.045). In conclusion, patients with higher age are more susceptible to CCAA suspected image and the significant variables found (CD4 nadir and LPV/r) are compatible with the cardiovascular risk factors in patients HIV+, related both to the severity of the infection and the use of antiretroviral.

Estudos recentes sugeriram associação entre doença periodontal e doenças cardiovasculares e respiratórias. O objetivo deste estudo foi investigar a presença de bactérias periodontopatogênicas em placas ateromatosas humanas. Foram incluídos no estudo 24 pacientes de ambos os sexos, 40-60 anos de idade, internados na UTI do Hospital Nossa Senhora da Conceição em Tubarão-SC com indicação para endarterectomia. Após a coleta das placas ateromatosas, procedeu-se a identificação de sete diferentes espécies bacterianas periodontopatógenos por meio da reação em cadeia da polimerase em tempo real (RT-PCR). Para realização da análise estatistica foi verificada a associação entre as duas variáveis qualitativas nominais (presença ou ausência de bácterias X tipo de bactérias) por meio do teste Qui-quadrado, com nível designificância de 5 %. Os resultados desse trabalho mostraram haver associação entre presença ou ausência de bactérias e dos diferentes tipos de bactérias nos ateromas analisados (p = 0001). Dos ateromas avaliados 75% apresentaram Porphyromonas gingivalis., 58,3% Treponema denticola., 37,5% apresentaram Fusobacteriumnucleatum., 33,3% Prevotella intermedia., 20,8% Agreggatibacter actinomycetencomitanse. 0,4% de Prevotella nigrescens. Esses achados permitem concluir que bactérias periodontopatogênicas apresentam a capacidade de invadir a parede das artérias, podendo ter papel significativo no desenvolvimento ou ruptura das placas ateroescleróticas. / Recent studies suggested an association between periodontal disease and cardiovascular and respiratory diseases. The aim of this study was to investigate the presence of periodontopathogens in human atherosclerotic plaque. It were included in this study 24 non-smoking patients, both genders, 40-60 years, admitted at intensive unit care with indication of endarterectomy. After collection of carotid samples containing the lesions, the identification of seven different bacterial species was performed by real time polymerase chain reaction (RT-PCR). For statistical analysis, the association between two nominal qualitative variables (presence or absence of bactérias vs. bacterial specieis) was verified by Chi-squared test, with a 5% significance level. The results obtained showed an association between the presence or absence and bacterial species found in atheroma (p= .0001). Among the atheroma examined, 75% showed the presence of Porphyromonas gingivalis, 58.3% showed Treponema denticola, 37.5% showed Fusobacteriumnucleatum, 33.3% showed Prevotella intermedia, 20.8% Agreggatibacter actinomycetencomitans and 0.4% Prevotella nigrescens. These findings suggest that periodontopatoghens are capable of invading artery wall and could play a significant role in the development or rupture of atherosclerotic lesions.